Open access peer-reviewed chapter

Importance of Nanoparticles in Cancer Therapy and Drug Delivery: A Detailed Theory and Gaps

Written By

Sagarkumar Patel and Rachna Patel

Reviewed: 12 September 2023 Published: 29 September 2023

DOI: 10.5772/intechopen.113189

From the Edited Volume

Drug Development and Safety

Edited by Abdur Rauf

Chapter metrics overview

78 Chapter Downloads

View Full Metrics

Abstract

Nanoparticles are a game-changing innovation in cancer therapy and drug delivery. Their ability to enhance drug targeting, overcome biological barriers, and minimize side effects makes them a cornerstone of modern oncology. The challenge lies in effectively distinguishing cancer cells from their regular counterparts in cancer therapy. Nanotechnology has emerged as a transformative solution, addressing this challenge through precise treatment modalities. This chapter delves into the pivotal role of Nanoparticles (NPs) in cancer therapy, primarily focusing on their significance in the drug delivery process. Overcoming the hurdles posed by conventional treatments, the genomic instability of tumors contributes to the variability among cancers, resulting in chemoresistance that challenges therapeutic success. A pioneering deep learning approach coupled with NPs has been proposed to tackle these issues, outshining previous methodologies by delivering drugs with accurate precision to target cancer cells and tissues. Through this innovative deep-learning technique, the proposed model achieves exceptional outcomes. With a remarkable accuracy of 97.591%, sensitivity of 96.644%, and specificity of 96.415%, the deep learning-enabled NPs demonstrate efficiency compared to the modern methods. This proposed model ushers in a new era of hope for patients and clinicians in the fight against cancer.

Keywords

  • deep learning
  • nanoparticles
  • drug resistance
  • cancer
  • nanotechnology
  • chemotherapy

1. Introduction

This section elaborates on the contemporary fusion of Nanotechnology and Artificial Intelligence in cancer therapy while elucidating the challenges inherent in diverse cancer treatments and the gamut of NPs employed in such therapeutic endeavors. The World Health Organization (WHO) estimates cancer’s dire impact, ranking it the second dominant cause of global human mortality, accounting for approximately 10 million annual deaths [1]. This generic term encompasses a broad spectrum of diseases relentlessly afflicting the human body, often leading to fatal outcomes. In neoplasms, cancers manifest as uncontrolled proliferation of infected cells, potentially invading healthy neighboring cells, rendering the disease refractory to treatment. Accumulation beyond cell limits or avoidance of programmed cell death characterizes cancer, affecting various body parts. Cancers are broadly categorized as benign and malignant. Benign cancers grow slowly with distinct borders, while malignant cancers transgress boundaries, infiltrating adjacent cells. Carcinoma, sarcoma, leukemia, and lymphoma are prominent cancer types, further subcategorized based on origin. Early detection significantly improves prognosis, with indicative signs like fatigue, lumps, unexplained weight loss, skin changes, and persistent coughing. Breast cancers (BC) exemplify an aggressively metastatic variant, posing substantial therapeutic challenges [2]. Hormone therapy’s ineffectiveness drives patients toward systemic chemotherapy, yet non-specific drug diffusion post-administration produces undesirable toxic effects. Multidrug resistance stemming from impaired drug intake and augmented drug efflux compounds these challenges, necessitating the development of effective BC treatments.

1.1 Nano technology

Nanotechnology presents an exact avenue for directing therapeutic agents to specific cancer cells and tissues, proficiently ferrying chemotherapy, radiotherapy, and immunotherapy drugs to their intended destinations. Extensive research has contributed to the creation of targeted nanocarriers aimed at controlling the release of antitumor drugs. Leveraging the enhanced permeation and retention (EPR) effect, investigators have formulated diverse NP platforms, including liposomes, polymer NPs, dendrimers, and so on, to transport anti-cancer agents into tumor tissues. Nonetheless, the effect of EPR alone does not suffice to eliminate cytotoxic drug side effects and ensure accurate anti-cancer drug delivery to cancer cells [3]. To augment targeting precision and uptake efficiency, NPs’ external surfaces are often adorned with various ligands, significantly enhancing interactions between nanocarriers and cancer cells. These ligands encompass targeted agents such as antibodies, peptides, and small molecule compounds like folic acid. The recent past has witnessed extensive exploration of controlled drug delivery systems in the anti-cancer domain. An ideal drug delivery system must possess stability to retain loaded anti-cancer drugs during bloodstream circulation or in normal tissues. Both passive and active targeting mechanisms come into play for effective drug targeting and accumulation within tumor tissues. Once taken up by cancer cells, immediate drug release in response to the local environment is crucial [4]. The adaptability and responsiveness of stimulation-responsive polymer NPs have found widespread utility in tumor cell targeting, given their capacity to adjust to the tumor microenvironment.

1.2 Significance of therapy

Numerous cancer treatments have been developed, yet many have not realized their full potential in saving lives, underscoring the persistent global challenge of discovering innovative cancer therapies. Current cancer treatment modalities encompass a range of options involving surgery, chemotherapy, radiation therapy, immunotherapy, and so on. However, the lack of precise targeting of tumor cells undermines the efficacy of cancer treatments. Moreover, the necessity for higher drug doses to reach specific target cells often results in toxic effects within the human body. While chemotherapy is a widely employed cancer treatment method globally, it presents challenges. Its mechanisms for eliminating malignant cells also affect healthy cells, resulting in serious repercussions such as bone marrow suppression, hair loss, and gastrointestinal issues [2]. Thus, the central focus of numerous research endeavors in cancer treatment lies in developing therapies that target tumor cells without harming healthy cells, aiming to alleviate these treatment-associated concerns.

Chemotherapy treatment uses potent chemicals to halt the growth of tumors by delivering anti-cancer drugs directly to them [2]. It is effective against fast-growing cancer cells due to their quicker replication. Immunotherapy harnesses the body’s natural defense system and enhances the immune response to identify and eliminate cancer cells. It can be used alone or combined with other treatments like chemotherapy. Biomarker testing involves analyzing genes, proteins, and other substances unique to an individual’s cancer to tailor treatment approaches. Drugs are developed based on the specific biomarker pattern of the cancer. Biomarker testing involves analyzing genes, proteins, and other substances unique to an individual’s cancer to tailor treatment approaches. Drugs are developed based on the specific biomarker pattern of the cancer. By manipulating hormones, this Hormone Therapy treatment restricts tumor growth. It can involve suppressing, blocking, or adding particular hormones to the body. Radiation therapy destroys cancer cells by using intense radiation beams, often X-rays and laser beams. Proton radiation is also employed to target cancer cells effectively. A cancer surgery involves removing tumors from the body, occasionally necessitating the removal of adjacent healthy tissue to control cancer spread [2].

1.3 Role of artificial intelligence in cancer therapy

Artificial Intelligence enabled by deep learning furnishes the vision-based technologies and prediction of patterns utilized in cancer therapy. In the particular area of bioinformatics, deep models can detect complex patterns in medical datasets to produce accurate insights and predictions. In biomedical imaging, deep learning is applied for several tasks, such as segmentation of tumor-affected tissue imaging [5]. For example, the tumor-affected blood cells can be predicted by employing a modified CNN architecture to target the cells to assist the NPs loaded with anti-cancer drugs to inhibit the cancer. Other models focus on easing data collection, and often, deep CNNs are trained for cell segmentation to formulate labeled datasets automatically utilizing fluorescently labeled cells. Hence, the most significant problem of deep learning models is the requirement for large annotated datasets to be collected by experts. To eliminate this problem, artificial NPs datasets are created, accelerating the data collection by forming annotated datasets without requiring expert manual annotations. Finally, in association with the object reconstruction, incorporating NPs for cancer targeting and deep models assisted the sophisticated systems that further classified the cancer and determined the complex disease patterns. Additionally, AI techniques help in biomarker detection, predicting interactions of NPs with the targeted drug, and evaluating drug efficacy.

1.4 Role of NPs in cancer therapy

Nanotechnology has emerged as the best solution for various medical applications due to its capability to deal with the dimensions and tolerances of less than 100 nanometers specifically for tackling individual molecular sizes [6]. Nanotechnology offers the exact approach to delivering the drugs into the target cells and tissues. With the assistance of these tools, medical experts can effectively transfer chemotherapy, radiotherapy, and immunotherapy drugs into the infected cells of the human body [7]. NPs are tiny elements that have size ranges from 1 to 100 nm. These NPs are categorized into multiple classes based on their shapes, sizes, and properties. The different types of NPs include metal NPs, ceramic NPs, and polymeric NPs. Additionally, the NPs possess specific properties because of high surface area and nano-scale size [8]. The physical properties relevant to the size and different colors are observed due to the absorption of NPs in the visible region [9]. Hence, the physiochemical properties enabled the NPs to be employed in medical applications like cancer treatment.

1.4.1 Types of NPs for cancer therapy

1.4.1.1 Organic NPs

Organic NPs are formed with the configuration of organic molecules that are virtually infinite numbers of unique structures or polymers. These organic materials are used in wide applications due to the ease of fabrication and the wide range of amassed structures that furnish better biocompatibility and biodegradation that make them suitable for drug delivery [10, 11, 12]. Additionally, the organic NPs provided antitumor efficacy and improved bioavailability compared to other NPs. Some organic NPS include dendrimers, polymeric NPS, liposomes, nanoemulsions, etc.

Polymeric NPs, structured through diverse monomers, range from 1 to 1000 nm [13]. They can encapsulate or adsorb active substances within their polymeric core for drug delivery. These hyperbranched NPs [14] have adjustable branches, aiding nucleic acid-targeting. Examples include polyamidation, with sizes ranging from 1 to 10 nm. Monoclonal antibody NPs, forming antibody-drug conjugates, precisely target cancer cells [15]. Paclitaxel core with a modified surface enhances efficiency and reduces toxicity. Extracellular Vesicles (EVs): From 50 to 1000 nm, EVs are lipid vesicles discharged by cells, like exosomes, macrovesicles, and apoptotic bodies. Exosomes penetrate cancer cells, delivering cytotoxic drugs. Spherical vesicles encapsulate drugs with a hydrophilic core and phospholipid bilayer. Low toxicity and inertness characterize liposomes. Cyclodextrin Nano sponges: These tiny NPs enhance drug loading, stabilizing and solubilizing agents like camptothecin drugs within cyclodextrin-based nanosponges.

1.4.1.2 Inorganic NPs

While compared with organic NPs, inorganic NPs possess the merits of maximum surface area to volume ratio and are safe as well as biocompatible and stable [6]. The most commonly used inorganic NPs involve gold NPs, carbon nanotubes, quantum dots, and magnetic NPs.

  1. Carbon NPs: These are carbon-based NPs widely employed for their optical and electronic properties and biocompatibility. These NPs encapsulate the drugs through π-π stacking due to their hydrophobic nature. Carbon NPs include graphene, fullerenes, carbon nano horns, etc.

  2. Quantum Dots: The quantum dots are semiconductors with a broad spectrum of absorption and narrow emission bands that make them applicable to biological imaging. The graphene quantum is utilized highly in drops because of their high intrinsic biocompatibility and discharge.

  3. Metallic NPs are highly investigated in biological imaging and targeted in cancer cells because of their extraordinary optical, magnetic, and photothermal properties [13]. Generally utilized metallic NPs are silver NPs, iron-based NPs [16], gold NPs, and so on. Moreover, gold NPs are employed for intracellular targeting due to their tiny size and surface coating. The silver NPs (Ag NP) stimulated the ROS generation that inhibited the ATP synthesis and destroyed the cancer cells without damaging the healthy cells, as the normal cells are more resistant to cancer therapies.

  4. Magnetic NPs: These are typically used in MRI imaging and as a carrier for drugs comprising metal and metal oxides and are enveloped with polymers and fatty acids to improve stability and compatibility. Magnetic NPs are also employed for targeted cancer therapy like magnetic hyperthermia, gene therapy, and controlled drug delivery [17, 18, 19].

  5. Calcium Phosphate NPs: These are biologically compatible, biodegradable, and non-toxic, making them suitable for the delivery of antibiotics, growth factors, etc. Calcium phosphate can be combined with viral and non-viral vectors as carriers for gene transfer [20].

  6. Silica NPs: Silica NPs are employed for delivering the genes by formulating the surface coating with amino-silicanes and are broadly used in immunotherapy due to minimal toxicity [21, 22].

1.4.1.3 Hybrid NPs

Hybrid NPs are high-potential heat transfer NPs acquired from suspending two or more dissimilar NPs in a regular heat transfer liquid [6]. Due to the high heat transfer properties of hybrid NPs, integrated different NPs advantages are widely used in industrial, manufacturing, and biomedical imaging processes [18].

  1. Lipid-polymer hybrid: These are NPs comprising polymer cores and lipid/lipid-PEG shells that reveal the contrast characteristics of liposomes and polymeric NPs, uniquely in terms of their stability and biocompatibility [6, 15, 23].

  2. Organic-inorganic hybrid: These hybrid NPs merge the variability of organic materials with the profiles often associated with inorganic materials. Hybrid NP comprises a silica core with an encapsulating lipid bilayer and is synthesized and validated in transferring the drugs to destroy the prostate and breast cancer cells [21, 24, 25, 26].

  3. Cell membrane coating hybrid: These hybrid NPs are synthesized to rectify cancer. Cell membranes are derived from multiple natural cells and forced to encapsulate around different NPs to activate the immune response and targeting mechanism [27].

1.4.2 Synthesis of NPs

Multiple synthesis methods are adopted according to the different shapes, sizes and properties of the NPs [28, 29, 30, 31]. The forms are categorized into two groups that include the approaches as follows.

1.4.2.1 Bottom-up approach

The method concerns building materials from atoms to clusters and further to NPs, which is the process of building the NPs from simpler particles, otherwise known as the constructive approach [13]. The generally employed techniques include spinning, sol–gel synthesis, vapor deposition, flame spraying, etc. (Figure 1).

Figure 1.

Synthesis of NPs with top-down and bottom-up techniques.

1.4.2.2 Top-down approach

This method is also known as a destructive approach that depletes the heavy materials to synthesize the NPs. The more giant molecules are reduced into small blocks and converted into NPs [13]. The methods involve milling, nanolithography, laser ablation, and so on. Additionally, the characteristics related to the structure can be altered by changing the condition and other synthesized parameters. An in-depth knowledge of growth mechanisms is required for synthesizing the NPs.

1.4.3 Drug resistance operation

The drug resistance exhibited by tumor cells is a significant drawback of conventional therapies in cancer treatment, where the genomic instability aids the tumor to identify the heterogeneity between the cancers that progress the drug resistance of cancer cells [32]. The cancer cells acquire resistance to the drugs as the genes encoding the sequence of amino acids of proteins develop the mutation that can tolerate the changes according to the drugs injected in the tumor cells. The drug resistance mechanism includes the factors responsible for the drug resistance, such as efflux transporters, apoptosis process, and hypoxia response [33, 34, 35, 36].

1.4.3.1 Focused approach to P-gp efflux transporter targeting

The efflux transporters reduce the drug accumulation by forcing the drugs out of the tumor cell, causing therapy failure. Glycoprotein is the most observed efflux transporter [23]. The high level of P-gp efflux transporters results in the inefficient treatment of the cancer [32]. The lipid phase of the plasma membrane plays a significant role in drug resistance as lipids can influence the proteins inside the plasma membrane by the membrane thickness. The membrane thickness affects the drug delivery, which can be reduced by combination therapy where the drugs are assembled within a single NP for drug delivery [37, 38, 39].

1.4.3.2 Targeting the process of apoptosis

The reactive oxygen species (ROS) formation in the mitochondria destroys the proteins, cell membranes, and DNA through the process of apoptosis, and the defective apoptosis process causes drug resistance in tumor cells [32]—the apoptosis process influenced by the lipids involved in the process. The drug-resistance cells preserve intracellular ceramide levels by enhancing the sphingomyelinase synthesis or reducing SM breakdown. Additionally, Adriamycin-resistant maintained ceramide level by multiplying the copies of an enzyme that converts ceramide to anti-apoptotic. Hence, combined therapies can be adopted to eliminate drug resistance in such conditions [40].

1.4.3.3 Targeting hypoxia response

Hypoxia is the situation determined at which the tumor cells are found with deprived oxygen levels. As a tumor grows, it requires a high blood supply, leaving portions where the oxygen concentration is reduced with the healthy cells. Hence, the enhanced interaction between the ceramide molecules forms the phase separation. The cells slowly multiplied in the hypoxic areas and avoided with cytotoxic drugs like alkylation agents and antibiotics [32]. The combined chemo-immunotherapy drugs delivery into perforated silicon NPs effectively stimulate the activation, cytotoxicity, and immune response against cancer cells.

Advertisement

2. Literature review

This section reviews recent methods, motivating the researchers to form the remarkable contributions of cancer therapy enabled by the deep learning model.

Anton Cid-Mejias et al. [5] developed a deep learning approach for segmenting the NPs in cancer therapy where the annotated datasets are created, followed by two CNNs for detecting and segmenting the NPs with their orientation. Finally, the reconstruction detected the shape of the nanoparticles utilized in the therapy. The approach does not require the annotated database and is adaptable but focused on the generated data validation.

Lei Liu et al. [14] developed a deep learning technique for analyzing the cytotoxicity of the Ag NPs where the decision tree is utilized in the model to facilitate the binary classification of the data and different combinations of features were extracted that provided the details involving the size, extraction solvent, exposure dose, and exposure time of NPs in cancer therapy were evaluated. The ensemble methods involving the random forest and the decision tree were utilized for the multi-classification of the NPs. However, these attributes do not accurately classify cytotoxicity, as the characteristics of silver NPs are complex to compute.

Yang Shen et al. [41] suggested an SVM classification for cancer therapy in which the gene expression data is utilized for the diagnosis. The method where the elastic net and fused lasso provided the smoothness and oriented features were selected automatically, reducing the time consumption. However, the technique has low reliability, and the complexity of the model should be minimized.

Alexandros Laios et al. [42] developed the k-NN classifier for cytotoxic prediction in cancer therapy, where the nearest neighbors are determined by the intake variables, and the average growth is predicted. The optimum neighbors were evaluated based on error calculation. The method provided the feasibility using the k-NN approach and outperformed the logistic regression while the value of k increased, causing the overfitting problems.

Aman Chandra Kaushik et al. [43] developed an optimized deep neural network for evaluating the growth receptor bound with gold NPs for cancer therapy. The approach where the mutational details of the receptor units utilized in the method were retrieved furnished insights for the cancer cell targeting and proved the efficiency of the gold NPs in inhibiting the growth factor receptor by the synergistic effect against the growth factor. Finally, the drug delivery efficiency of the gold NPs for smooth targeting of the cancer cells was determined.

Yousef Nademi et al. [44] suggested a deep learning method for non-viral vector anti-cancer drug delivery. The approach where the Polyethyleneimine NPs with anti-cancer drug siRNA are transferred to the cancer cells by utilizing the deep classifiers including the random forest, perceptron, and regression network. The approach in which the average prediction value is computed from the decision tree. Then, the perceptron and random forest better predicted the target cells due to the non-linearity that stated that the chemical descriptors would further facilitate better drug delivery into the cancer cells.

Huimin Zhu et al. [45] developed the simulation of anti-cancer drugs utilizing the machine learning model where the Fuzzy inference system employed in the approach that split the evaluated data for training and testing that further analyzed the solubility of the busulfan in the supercritical carbon dioxide. The fuzzy inference integrated the grid partitioning technique for providing the accurate processing parameters that drive the solvent solubility in the medium. However, the model’s reliability should be further improved in the method.

Min Li et al. [46] developed the deep model approach for drug sensitivity detection in cancer therapy. The method where the genomic features and information related to the chemicals in drug constituency was integrated and analyzed using the modified deep model known as Deep DSC that predicted the sensitivity of the cancer lines. The Deep DSC method provided the advantages of interpolating the unknown drug sensitivity values and fewer extrapolating errors. However, the model’s root mean square values of leave one tissue out and compound out values are less.

Challenges:

  • Most cancer therapies observe the challenges in drug resistance exhibited by the tumor cells, where the genomic instability of the tumor provides the heterogeneity between the cancers that progress the chemoresistance of cancer cells [14].

  • However, the attributes, including the size, extraction solvent, exposure dose, and exposure time, do not accurately classify Ag NPs cytotoxicity as the characteristics of silver NPs are complex to compute and should be improved [14, 32].

  • The deep learning method utilizing the k-NN classifier for cancer diagnosis performed the logistic regression. At the same time, the value of k increased, which caused the overfitting problems that caused the error in the accurate prediction of cancer cells [42].

  • The major drawback of the complexity associated with cancer treatment is cancer’s metastatic nature, which causes errors in the prediction models enabled with the deep learning methods [44].

The cancer therapies in the former methods with their merits and demerits are elaborated in Section 2, and the deep learning enabled NPs for cancer therapy are enumerated in Section 3. The performance and analysis of proposed deep learning-enabled NPs for cancer therapy are elaborated in Section 4, and the conclusion is depicted in Section 5.

Advertisement

3. Proposed deep learning enabled NPs for cancer therapy

3.1 Deep convolutional neural network (DCNN)

DCNN is a sub-type of neural network that takes the merits of the spatial structure of the inputs for predicting the cancer cells by segmenting the cancer cells from the healthy cells. CNN models comprise the stacked convolutional layers and pooling layers, where each pooling layer is located after a convolutional layer. When applied to cancer prediction, CNNs can automatically acquire prominent features from the input data comprising the cancer and healthy cells and detect the patterns associated with the cancer cells that assists the NPs in accurately targeting the cancer cells for delivering the drugs in the targeted cells. CNN provided the segmentation of tumor cells by creating ground truth labeled datasets, thereby reducing the annotation requirement. The convolution layers learn the features of the cancer cells from the trained instances. They are utilized for predicting the cancer cells from the normal cells that are further processed, enabling the deep learning allowed NPs to target the tumor cells for delivering the drugs. CNN was employed for segmentation of the cancer cells from the microscopic images where the white blood cells affected with cancer can be determined by the CNN model for prominent targeting by NPs.

3.2 Targeting mechanism of Nps enabled with deep learning in cancer therapy

Deep CNN can learn the hierarchical representation of the data that overcame the recent methods as they optimize the filters to acquire the characteristic features from images. Hence, the deep CNN used to predict cancer cells enables the NPs to target the cancer cells. NPs are a non-toxic and effective approach for cancer diagnosis, anti-cancer drug delivery, and treatment. The combined NPs with chemotherapy drugs are injected into the infected cells for cancer treatment. NPs can deliver the insoluble drugs into the confined and distant tumor sites while protecting the drugs from being released prematurely. Hence, the nanoparticles eliminate the side effects associated with conventional therapy techniques. NPs are selected based on their size, surface coating, and other chemical properties for effective drug delivery [32]. NPs target the mitochondria that synthesize adenosine triphosphoric acid (ATP) that is required to replicate the cancer cells. The NPs combination of anti-cancer drugs promotes ROS generation in the mitochondria, destroying the mitochondrial proteins, cell membranes, and DNA strands replication through apoptosis that inhibits the cancerous cell multiplication [15, 21, 40, 47].

Often, it is observed that the Ag NPs that stimulated the ROS generation inhibited the ATP synthesis and destroyed the cancer cells without any damage to the healthy cells, as the normal cells are more resistant to the cancer therapies.

3.3 Targeting through passive means

Passive targeting depends on the EPR effect, where the targeting is exhibited during the hypoxia condition or the inflammation as the endothelium layers become more permeable during the neovascularization period [13]. While the hypoxia condition exists, the growing tumor cells utilize more perforated blood vessels as they possess more holes, thereby causing the permeability of the blood vessels. Additionally, the blood vessels become less resistant to extravasations, allowing the NPs to get diffused within the blood vessels and accumulate within the tumor cells. The primary factor responsible for cell replication is the glycolysis process that causes the tumor environment to be acidic due to low pH, and this period can be utilized to release the anti-cancer drugs encapsulated with the pH-sensitive NPs targeting the tumor cells (Figure 2) [47].

Figure 2.

Passive targeting.

3.4 Active targeting

Active targeted NPs deliver a certain quantity of drugs to targeted tumor cells within a particular organ in the body. Drug-loaded NPs, along with ligands, are utilized for identification by receptors on cancer cells to eliminate the non-specific distribution of drugs in the entire body cells and eliminate cytotoxicity and impacts of drugs on healthy cells and organs that it is impossible in traditional chemotherapy [32]. Active targeting highly relies on ligands like folate that bind to the receptors over the surface layers of tumor cells. NPs with ligands furnish the retention and accumulation of drugs in the target cells. The mechanism involves the identification of ligands by the target receptors on the tumor surface that differentiate the tumor cells from the healthy cells. The ligands like peptides, antibodies, nucleic acids, vitamins, and so on can bind with the NPs and actively target the cancer cells (Figure 3).

Figure 3.

Active targeting.

Advertisement

4. Results and discussion

The proposed deep learning framework enabled with NPs for cancer therapy is executed, and the model outcomes are enumerated in the section to reveal the model’s efficacy.

4.1 Experimental setup

The research is executed in Python, which comprises several programming methods; for instance, efficient programming and configuration of a system for the implementation involves PyCharm software running in the Windows 10 Operating System with 8GB internal RAM.

4.2 Dataset description

4.2.1 Breast cancer browse dataset

The datasets are collected from the breast cancer browse dataset in the UCI machine learning repository that contains multivariate images of about 286 instances with nine attributes for the validation testing and training of the deep models to provide efficient cancer diagnosis and cancer therapy utilizing the NPs [48].

4.2.2 SACT dataset

SACT datasets are collected from the SACT database organized by the Team of National Disease Registration Service (NDRS) at NHS England. It contains 44 data items that comprise the patient and tumor features, trust and consultant details, treatment characteristics, including drug specifications, and their combinations for training and testing of the datasets to provide efficient cancer therapy [49].

4.3 Performance analysis

The analysis of performance related to the deep learning-enabled NPs for cancer therapy is evaluated by employing the performance metrics, including the accuracy, sensitivity, and specificity described as follows.

4.3.1 Performance analysis for deep learning model enabled NPs for cancer therapy

The performance results of the deep learning helped NPs for cancer therapy, considering different epoch values, are depicted in Figure 4. In Figure 4(a), the accuracy outcomes for TP 90, using the deep learning model, are as follows: 94.56%, 95.07%, 96.14%, 96.14, and 97.21% for epoch values of 100, 200, 300, 400, and 500, respectively. Correspondingly, Figure 5(b) displays the sensitivity values for TP 90, where the deep learning model achieves 94.77%, 95.12%, 95.85%, 95.85%, and 96.58% for epoch values of 100, 200, 300, 400, and 500, respectively. Likewise, Figure 5(c) shows cases of specificity over TP 90. The deep learning model demonstrates specificity values of 91.21%, 92.13%, 94.07%, 94.07%, and 96.01% for epoch values of 100, 200, 300, 400, and 500, respectively.

Figure 4.

Performance analysis for the proposed deep learning enabled NPs for cancer therapy.

Figure 5.

Comparative analysis of the proposed method: a) accuracy, b) sensitivity, c) specificity.

4.4 Comparative analysis

The comparative analysis of the deep learning enabled by NPs and different competent methods for cancer therapy is evaluated by employing the performance metrics described as follows.

4.4.1 Comparative analysis for deep learning model enabled NPs for cancer therapy

The comparative evaluation is estimated, and the result is acquired in terms of metrics depicted in Figure 5, in which the accuracy of the proposed method at TP 90 is 97.59%, which is enhanced by 8.5% to the former method D1, 2.77% to D2, 5.54% to D3, 6.104% to D4, 7.88% to D5, and 8.55% to D6. Moreover, the sensitivity at TP 90 is valued as 96.64%, which is progressed by 5.85% from the former method D1, 5.39% from D2, 11.25% from D3, 4.17% from D4, 3.79% from D5 and 1.901% from D6 as well as the specificity rate is 96.41% at TP 90 which is further progressed by 15.88% than D1, 14.64% than D2, 11.32% than D3, 10.29% than D4, 5.15% than D5 and 3.09% than D6 correspondingly. The analysis validated that the performance of the deep learning model is superior to the former methods. The systematic depiction of the comparative evaluation is demonstrated in Figure 5.

4.5 Comparative discussion

The evaluation of the deep learning-enabled NPs technique is enclosed in detail. Random Forest, KNN classifier, CATboost classifier, BiLSTM classifier, and deep CNN classifier are the former techniques employed for comparative evaluation. The performance of the enhanced classifiers at the early estimation of cancer is depicted here. Table 1 represents the relative discussions of the deep learning-enabled NPs model with several existing systems.

MethodsTraining Percentage (%)
AccuracySensitivitySpecificity
Random Forest D189.27390.98381.101
KNN classifier D289.89191.42682.302
Catboost classifier D391.63392.60685.493
BiLSTM Classifier D492.17792.97586.491
Deep CNN classifier D594.87994.80791.445
LSTM Classifier D695.96395.54293.433
Proposed Deep learning enabled NP model97.59196.64496.415

Table 1.

Comparative discussion.

4.6 Applications

Deep learning algorithms integrate diverse data sources such as gene expression data (X), patient clinical data (C), and molecular characteristics (M). These inputs are analyzed to create a comprehensive patient profile (P), which captures crucial information about the patient’s condition. Using the patient profile (P), a deep learning model predicts the optimal therapeutic strategy (T). This strategy involves selecting suitable therapeutic agents, dosages, and administration schedules tailored to the patient’s specific characteristics. Deep learning generates nanoparticle design parameters (N) based on the therapeutic strategy (T). Parameters include attributes like the type of drug, optimal dosage, and selection of targeting ligands that enhance nanoparticle specificity to cancer cells. A deep learning model determines the efficiency of nanoparticles’ targeting (TE). This model considers the expression of specific biomarkers (B) on cancer cells to calculate targeting efficiency. The eq. TE = f(B) captures this relationship. The release profile of therapeutic agents from nanoparticles (R) is modeled through deep learning algorithms. PH (pH) and temperature (T) influence the release kinetics. The eq. R = g (pH, T) characterizes the payload release process. Imaging data (I) obtained from techniques like MRI provides real-time feedback on the distribution of nanoparticles within the tumor.

Deep learning models analyze this data to assess and visualize the spatial distribution and effectiveness of treatment. Deep learning models utilize patient-specific data (P) to predict the likely treatment response (TR). Factors such as patient history, molecular characteristics, and treatment specifics contribute to predicting how the patient will respond to therapy. The eq. TR = h(P) captures this prediction. As the patient progresses through treatment, new patient data (P_new) is continuously fed into the deep learning model. This adaptive approach ensures that the therapeutic strategy (T) is dynamically adjusted based on evolving patient characteristics, maximizing treatment efficacy. Deep learning models provide clinicians with valuable insights (I), aiding them in making informed decisions about treatment adjustments and patient management. These insights contribute to an ongoing and collaborative treatment approach.

Advertisement

5. Conclusion

The proposed deep learning method enabled by NPs overcame the challenges of the former methods in precisely delivering drugs to the affected cancer cells. Further, the deep learning methods support the discrimination between the cancer cells and normal cells and address the problems associated with the conventional chemotherapy of NPs. The deep CNN is employed for predicting the cancer cells by detecting the cancer cell patterns that enabled the NPs to target the cancer cells prominently. This research specifically focuses on the significance of NPs in cancer therapy, particularly in the drug discovery process. The proposed deep learning method enabled by NPs overcame the challenges of drug resistance and provided an exact approach for drug delivery to the target cancer cells and tissues. The proposed deep learning method enabled with NPs delivered the performance of 97.591% accuracy, 96.644% sensitivity, and 96.415% specificity, which is more efficient when compared to the recent methods. Further, the method can be enhanced by utilizing other classifiers and augmentation methods.

References

  1. 1. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. International Journal of Cancer. 2021;149(4):778-789. DOI: 10.1002/ijc.33588
  2. 2. Pourmadadi M, Eshaghi MM, Ostovar S, Mohammadi Z, Sharma RK, Paiva-Santos AC, et al. Innovative nanomaterials for cancer diagnosis, imaging, and therapy: Drug delivery applications. Journal of Drug Delivery Science and Technology. 2023;82:104357
  3. 3. Huang Y. Targeting glycolysis for cancer therapy using drug delivery systems. Journal of Controlled Release. 2023;353:650-662
  4. 4. Das CA, Kumar VG, Dhas TS, Karthick V, Kumar CV. Nanomaterials in anti-cancer applications and their mechanism of action-a review. Nanomedicine: Nanotechnology, Biology and Medicine. 2023;47:102613
  5. 5. Cid-Mejías A, Alonso-Calvo R, Gavilán H, Crespo J, Maojo V. A deep learning approach using synthetic images for segmenting and estimating 3D orientation of nanoparticles in EM images. Computer Methods and Programs in Biomedicine. 2021;202:105958
  6. 6. Dang Y, Guan J. Nanoparticle-based drug delivery systems for cancer therapy. Smart Materials in Medicine. 2020;1:10-19
  7. 7. Jafari S, Derakhshankhah H, Alaei L, Fattahi A, Varnamkhasti BS, Saboury AA. Mesoporous silica nanoparticles for therapeutic/diagnostic applications. Biomedicine & Pharmacotherapy. 2019;109:1100-1111
  8. 8. Rane AV, Kanny K, Abitha VK, Thomas S. Methods for synthesis of nanoparticles and fabrication of nanocomposites. In: Synthesis of Inorganic Nanomaterials. Durban: Woodhead Publishing; 2018. pp. 121-139
  9. 9. Ziental D, Czarczynska-Goslinska B, Mlynarczyk DT, Glowacka-Sobotta A, Stanisz B, Goslinski T, et al. Titanium dioxide nanoparticles: Prospects and applications in medicine. Nanomaterials. 2020;10(2):387
  10. 10. Pandit C, Roy A, Ghotekar S, Khusro A, Islam MN, Emran TB, et al. Biological agents for the synthesis of nanoparticles and their applications. Journal of King Saud University - Science. 2022;34(3):101869. DOI: 10.1016/j.jksus.2022.101869
  11. 11. Khurana A, Tekula S, Saifi MA, Venkatesh P, Godugu C. Therapeutic applications of selenium nanoparticles. Biomedicine & Pharmacotherapy. 2019;111:802-812
  12. 12. Ottoni CA, Simões MF, Fernandes S, Dos Santos JG, Da Silva ES, de Souza RF, et al. Screening of filamentous fungi for antimicrobial silver nanoparticles synthesis. AMB Express. 2017;7(1):1-0
  13. 13. Gavas S, Quazi S, Karpiński TM. Nanoparticles for cancer therapy: Current progress and challenges. Nano-scale research letters. 2021;16(1):173
  14. 14. Liu L, Zhang Z, Cao L, Xiong Z, Tang Y, Pan Y. Cytotoxicity of photosynthesized silver nanoparticles: A meta-analysis by machine learning algorithms. Sustainable Chemistry and Pharmacy. 2021;21:100425
  15. 15. Mu J, Zhong H, Zou H, Liu T, Yu N, Zhang X, et al. Acid-sensitive PEGylated paclitaxel prodrug nanoparticles for cancer therapy: Effect of PEG length on antitumor efficacy. Journal of Controlled Release. 2020;326:265-275
  16. 16. Soetaert F, Korangath P, Serantes D, Fiering S, Ivkov R. Cancer therapy with iron oxide nanoparticles: Agents of thermal and immune therapies. Advanced Drug Delivery Reviews. 2020;163:65-83
  17. 17. Fariq A, Khan T, Yasmin A. Microbial synthesis of nanoparticles and their potential applications in biomedicine. Journal of Applied Biomedicine. 2017;15(4):241-248
  18. 18. Khan T, Ullah N, Khan MA, Nadhman A. Plant-based gold nanoparticles; a comprehensive review of the decade-long research on synthesis, mechanistic aspects, and diverse applications. Advances in Colloid and Interface Science. 2019;272:102017
  19. 19. Hasan A, Morshed M, Memic A, Hassan S, Webster TJ, Marei HE. Nanoparticles in tissue engineering: Applications, challenges, and prospects. International Journal of Nanomedicine. 2018:5637-5655
  20. 20. Khalifehzadeh R, Arami H. Biodegradable calcium phosphate nanoparticles for cancer therapy. Advances in Colloid and Interface Science. 2020;279:102157
  21. 21. He H, Meng S, Li H, Yang Q , Xu Z, Chen X, Sun Z, Jiang B, Li C. Nanoplatforms based on GSH-responsive mesoporous silica nanoparticles for cancer therapy and mitochondrial-targeted imaging. Microchimica Acta 2021; 188:1-0
  22. 22. Chen S, Greasley SL, Ong ZY, Naruphontjirakul P, Page SJ, Hanna JV, et al. Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy. Materials Today Advances. 2020;6:100066
  23. 23. Khan H, Mirzaei HR, Amiri A, Akkol EK, Halimi SM, Mirzaei H. Glyco-nanoparticles: New drug delivery systems in cancer therapy. In: Seminars in Cancer Biology. Vol. 69. Pakistan: Academic Press; 2021. pp. 24-42
  24. 24. She S, Chen H, Ji W, Sun M, Cheng J, Rui M, et al. Deep learning-based multi-drug synergy prediction model for individually tailored anti-cancer therapies. Frontiers in Pharmacology. 2022;13:1032875
  25. 25. Avanzo M, Stancanello J, Pirrone G, Sartor G. Radiomics and deep learning in lung cancer. Strahlentherapie und Onkologie. 2020;196:879-887
  26. 26. Snow O, Lallous N, Ester M, Cherkasov A. Deep learning modeling of androgen receptor responses to prostate cancer therapies. International Journal of Molecular Sciences. 2020;21(16):5847
  27. 27. Raj S, Khurana S, Choudhari R, Kesari KK, Kamal MA, Garg N, et al. Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. In: Seminars in Cancer Biology. Vol. 69. India: Academic Press; 2021. pp. 166-177
  28. 28. Eaton P, Quaresma P, Soares C, Neves C, De Almeida MP, Pereira E, et al. A direct comparison of experimental methods to measure dimensions of synthetic nanoparticles. Ultramicroscopy. 2017;182:179-190
  29. 29. Priyadarsini S, Mukherjee S, Mishra M. Nanoparticles used in dentistry: A review. Journal of Oral Biology and Craniofacial Research. 2018;8(1):58-67
  30. 30. Zhao D, Yu S, Sun B, Gao S, Guo S, Zhao K. Biomedical applications of chitosan and its derivative nanoparticles. Polymers. 2018;10(4):462
  31. 31. Sun T, Zhang YS, Pang B, Hyun DC, Yang M, Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Nanomaterials and Neoplasms. 2021:12320-12364
  32. 32. Miranda RR, Sampaio I, Zucolotto V. Exploring silver nanoparticles for cancer therapy and diagnosis. Colloids and Surfaces B: Biointerfaces. 2022;210:112254
  33. 33. Partin A, Brettin TS, Zhu Y, Narykov O, Clyde A, Overbeek J, et al. Deep learning methods for drug response prediction in cancer: Predominant and emerging trends. Frontiers in Medicine. 2023;10:1086097
  34. 34. Chang JW, Ding Y, Tahir ul Qamar M, Shen Y, Gao J, Chen LL. A deep learning model based on sparse auto-encoder for prioritizing cancer-related genes and drug target combinations. Carcinogenesis. 2019;40(5):624-632
  35. 35. Bychkov D, Linder N, Tiulpin A, Kücükel H, Lundin M, Nordling S, et al. Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy. Scientific Reports. 2021;11(1):4037
  36. 36. Wang S, Zhang H, Liu Z, Liu Y. A novel deep learning method to predict lung cancer long-term survival with biological knowledge incorporated gene expression images and clinical data. Frontiers in Genetics. 2022;13:800853
  37. 37. Paskeh MD, Entezari M, Clark C, Zabolian A, Ranjbar E, Farahani MV, et al. Targeted regulation of autophagy using nanoparticles: New insight into cancer therapy. Biochemicals et Biophysica Acta (BBA)-Molecular Basis of Disease. 2022;1868(3):166326
  38. 38. Peetla C, Vijayaraghavalu S, Labhasetwar V. Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles. Advanced Drug Delivery Reviews. 2013;65(13-14):1686-1698
  39. 39. Huda S, Alam MA, Sharma PK. Smart nanocarriers-based drug delivery for cancer therapy: An innovative and developing strategy. Journal of Drug Delivery Science and Technology. 2020;60:102018
  40. 40. Känkänen V, Fernandes M, Liu Z, Seitsonen J, Hirvonen SP, Ruokolainen J, et al. Microfluidic preparation and optimization of sorafenib-loaded poly (ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications. Journal of Colloid and Interface Science. 2023;633:383-395
  41. 41. Shen Y, Wu C, Liu C, Wu Y, Xiong N. Oriented feature selection SVM applied to cancer prediction in precision medicine. IEEE Access. 2018;6:48510-48521
  42. 42. Laios A, Gryparis A, DeJong D, Hutson R, Theophilou G, Leach C. Predicting complete cytoreduction for advanced ovarian cancer patients using nearest-neighbor models. Journal of Ovarian Research. 2020;13:1-8
  43. 43. Kaushik AC, Wang YJ, Wang X, Kumar A, Singh SP, Pan CT, et al. Evaluation of anti-EGFR-iRGD recombinant protein with GOLD nanoparticles: Synergistic effect on antitumor efficiency using optimized deep neural networks. RSC Advances. 2019;9(34):19261-19270
  44. 44. Nademi Y, Tang T, Uludağ H. Modeling uptake of Polyethyleneimine/short interfering RNA nanoparticles in breast cancer cells using machine learning. Advanced Nano Biomed Research. 2021;1(10):2000106
  45. 45. Zhu H, Zhu L, Sun Z, Khan A. Machine learning based simulation of an anti-cancer drug (busulfan) solubility in supercritical carbon dioxide: ANFIS model and experimental validation. Journal of Molecular Liquids. 2021;338:116731
  46. 46. Li M, Wang Y, Zheng R, Shi X, Li Y, Wu FX, et al. Deep DSC: A deep learning method to predict drug sensitivity of cancer cell lines. IEEE/ACM Transactions on Computational Biology and Bioinformatics. 2019;18(2):575-582
  47. 47. Li Y, Wang S, Song FX, Zhang L, Yang W, Wang HX, et al. A pH-sensitive drug delivery system based on folic acid-targeted HBP-modified mesoporous silica nanoparticles for cancer therapy. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2020;590:124470
  48. 48. UCI Machine Learning Repository [Internet]. archive.ics.uci.edu. [cited 2023 Sep 5]. Available from: https://archive.ics.uci.edu/datasets?search=cancer
  49. 49. Systemic Anti-Cancer Therapy (SACT) data set [Internet]. NDRS. [cited 2023 Sep 5]. Available from: https://digital.nhs.uk/ndrs/data/data-sets/sact

Written By

Sagarkumar Patel and Rachna Patel

Reviewed: 12 September 2023 Published: 29 September 2023