Metal-Organic Frameworks for Cisplatin Delivery to Cancer Cells: A Molecular Dynamics Simulation.

Metal-organic frameworks (MOFs) are utilized as nanocarriers to enhance the efficiency of chemotherapy drugs, including cisplatin, which exhibit limitations such as side effects and resistance mechanisms. To evaluate the role of MOFs, we employed a molecular dynamics simulation, which, unlike other experiments, is cost-effective, less dangerous, and provides accurate results. Furthermore, we conducted molecular docking simulations to understand the interaction between cisplatin and MOF, as well as their internal interactions and how they bind to each other. Cisplatin and MOF molecules were parametrized using the Avogadro software and x2top command in GROMACS 5.1.2 and optimized by CP2K software; the Charmm-GUI site parametrized the cell cancer membrane. Three molecular dynamics simulations were conducted in four stages at various pHs, followed by simulated umbrella sampling. The simulations analyzed the pH responsiveness, total energy, Gibbs free energy, gyration radius, radial distribution function (RDF), solvent accessible surface area, and nanoparticles' toxicity. Results demonstrated that a neutral pH level (7.4) has greater adsorption and interaction compared to acidic pH values (6.4 and 5.4) because it displays the highest total energy (-17.1 kJ/mol), the highest RDF value (6.66), and the shortest distance (0.51 nm). Furthermore, the combination of cisplatin and MOFs displayed increased penetration compared to that of their individual forms. This study highlights the suitability of MOFs as nanocarriers and identifies the optimal pH values for desirable outcomes. Thus, it provides future studies with appropriate data to conduct their experiments in assessing MOFs.

Chitosan- and hyaluronic acid-based nanoarchitectures in phototherapy: Combination cancer chemotherapy, immunotherapy and gene therapy.

Cancer phototherapy has introduced a new potential modality for tumor suppression. However, the efficacy of phototherapy has been limited due to a lack of targeted delivery of photosensitizers. Therefore, the application of biocompatible and multifunctional nanoparticles in phototherapy is appreciated. Chitosan (CS) as a cationic polymer and hyaluronic acid (HA) as a CD44-targeting agent are two widely utilized polymers in nanoparticle synthesis and functionalization. The current review focuses on the application of HA and CS nanostructures in cancer phototherapy. These nanocarriers can be used in phototherapy to induce hyperthermia and singlet oxygen generation for tumor ablation. CS and HA can be used for the synthesis of nanostructures, or they can functionalize other kinds of nanostructures used for phototherapy, such as gold nanorods. The HA and CS nanostructures can combine chemotherapy or immunotherapy with phototherapy to augment tumor suppression. Moreover, the CS nanostructures can be functionalized with HA for specific cancer phototherapy. The CS and HA nanostructures promote the cellular uptake of genes and photosensitizers to facilitate gene therapy and phototherapy. Such nanostructures specifically stimulate phototherapy at the tumor site, with particle toxic impacts on normal cells. Moreover, CS and HA nanostructures demonstrate high biocompatibility for further clinical applications.

Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy.

The combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive classes, have been introduced in cancer therapy. The tumor microenvironment remolds, and the acceleration of immunotherapy and vaccines can be provided by peptide nanoparticles. Moreover, the bioimaging and labeling of cancers can be mediated by peptide nanoparticles. Therefore, peptides can functionalize nanoparticles in targeted cancer therapy.

T Cell and Natural Killer Cell Membrane-Camouflaged Nanoparticles for Cancer and Viral Therapies.

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.

Autophagy flux in bladder cancer: Cell death crosstalk, drug and nanotherapeutics.

Autophagy, a self-digestion mechanism, has emerged as a promising target in the realm of cancer therapy, particularly in bladder cancer (BCa), a urological malignancy characterized by dysregulated biological processes contributing to its progression. This highly conserved catabolic mechanism exhibits aberrant activation in pathological events, prominently featured in human cancers. The nuanced role of autophagy in cancer has been unveiled as a double-edged sword, capable of functioning as both a pro-survival and pro-death mechanism in a context-dependent manner. In BCa, dysregulation of autophagy intertwines with cell death mechanisms, wherein pro-survival autophagy impedes apoptosis and ferroptosis, while pro-death autophagy diminishes tumor cell survival. The impact of autophagy on BCa progression is multifaceted, influencing metastasis rates and engaging with the epithelial-mesenchymal transition (EMT) mechanism. Pharmacological modulation of autophagy emerges as a viable strategy to impede BCa progression and augment cell death. Notably, the introduction of nanoparticles for targeted autophagy regulation holds promise as an innovative approach in BCa suppression. This review underscores the intricate interplay of autophagy with cell death pathways and its therapeutic implications in the nuanced landscape of bladder cancer.

Dysregulation of autophagy in gastric carcinoma: Pathways to tumor progression and resistance to therapy.

The considerable death rates and lack of symptoms in early stages of gastric cancer (GC) make it a major health problem worldwide. One of the most prominent risk factors is infection with Helicobacter pylori. Many biological processes, including those linked with cell death, are disrupted in GC. The cellular "self-digestion" mechanism necessary for regular balance maintenance, autophagy, is at the center of this disturbance. Misregulation of autophagy, however, plays a role in the development of GC. In this review, we will examine how autophagy interacts with other cell death processes, such as apoptosis and ferroptosis, and how it affects the progression of GC. In addition to wonderful its role in the epithelial-mesenchymal transition, it is engaged in GC metastasis. The role of autophagy in GC in promoting drug resistance stands out. There is growing interest in modulating autophagy for GC treatment, with research focusing on natural compounds, small-molecule inhibitors, and nanoparticles. These approaches could lead to breakthroughs in GC therapy, offering new hope in the fight against this challenging disease.

Nanomaterials in crossroad of autophagy control in human cancers: Amplification of cell death mechanisms.

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells.

Natural product/diet-based regulation of macrophage polarization: Implications in treatment of inflammatory-related diseases and cancer.

Macrophages are phagocytic cells with important physiological functions, including the digestion of cellular debris, foreign substances, and microbes, as well as tissue development and homeostasis. The tumor microenvironment (TME) shapes the aggressiveness of cancer, and the biological and cellular interactions in this complicated space can determine carcinogenesis. TME can determine the progression, biological behavior, and therapy resistance of human cancers. The macrophages are among the most abundant cells in the TME, and their functions and secretions can determine tumor progression. The education of macrophages to M2 polarization can accelerate cancer progression, and therefore, the re-education and reprogramming of these cells is promising. Moreover, macrophages can cause inflammation in aggravating pathological events, including cardiovascular diseases, diabetes, and neurological disorders. The natural products are pleiotropic and broad-spectrum functional compounds that have been deployed as ideal alternatives to conventional drugs in the treatment of cancer. The biological and cellular interactions in the TME can be regulated by natural products, and for this purpose, they enhance the M1 polarization of macrophages, and in addition to inhibiting proliferation and invasion, they impair the chemoresistance. Moreover, since macrophages and changes in the molecular pathways in these cells can cause inflammation, the natural products impair the pro-inflammatory function of macrophages to prevent the pathogenesis and progression of diseases. Even a reduction in macrophage-mediated inflammation can prevent organ fibrosis. Therefore, natural product-mediated macrophage targeting can alleviate both cancerous and non-cancerous diseases.

Implantable, 3D-Printed Alginate Scaffolds with Bismuth Sulfide Nanoparticles for the Treatment of Local Breast Cancer via Enhanced Radiotherapy.

Surgical removal of tumor tissue remains the primary clinical approach for addressing breast cancer; however, complete tumor excision is challenging, and the remaining tumor cells can lead to tumor recurrence and metastasis over time, which substantially deteriorates the life quality of the patients. With the aim to improve local cancer radiotherapy, this work reports the fabrication of alginate (Alg) scaffolds containing bovine serum albumin (BSA)-coated bismuth sulfide (Bi2S3@BSA) nanoradiosensitizers using three-dimensional (3D) printing. Under single-dose X-ray irradiation in vitro, Alg-Bi2S3@BSA scaffolds significantly increase the formation of reactive oxygen species, enhance the inhibition of breast cancer cells, and suppress their colony formation capacity. In addition, scaffolds implanted under tumor tissue in murine model show high therapeutic efficacy by reducing the tumor volume growth rate under single-dose X-ray irradiation, while histological observation of main organs reveals no cytotoxicity or side effects. 3D-printed Alg-Bi2S3@BSA scaffolds produced with biocompatible and biodegradable materials may potentially lower the recurrence and metastasis rates in breast cancer patients by inhibiting residual tumor cells following postsurgery as well as exhibit anticancer properties in other solid tumors.

Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer.

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.

Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-ß, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence.

Nanostructures for site-specific delivery of oxaliplatin cancer therapy: Versatile nanoplatforms in synergistic cancer therapy.

As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.

Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy.

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.

Electrochemical sensing of doxorubicin hydrochloride under sodium alginate antifouling conditions using silver nanoparticles modified glassy carbon electrodes.

Doxorubicin (DOX) is a highly effective anticancer drug with a narrow therapeutic window; thus, sensitive and timely detection of DOX is crucial. Using electrodeposition of silver nanoparticles (AgNPs) and electropolymerization of alginate (Alg) layers on the surface of a glassy carbon electrode, a novel electrochemical probe was constructed (GCE). The fabricated AgNPs/poly-Alg-modified GCE probe was utilized for the quantification of DOX in unprocessed human plasma samples. For the electrodeposition of AgNPs and electropolymerization of alginate (Alg) layers on the surface of GCE, cyclic voltammetry (CV) was used in the potential ranges of -2.0 to 2.0 V and -0.6 to 0.2 V, respectively. The electrochemical activity of DOX exhibited two oxidation processes at the optimum pH value of 5.5 on the surface of the modified GCE. The DPV spectra of poly(Alg)/AgNPs modified GCE probe toward consecutive concentrations of DOX in plasma samples demonstrated wide dynamic ranges of 15 ng/mL-0.1 µg/mL and 0.1-5.0 µg/mL, with a low limit of quantification (LLOQ) of 15 ng/mL. The validation results indicated that the fabricated electrochemical probe might serve as a highly sensitive and selective assay for the quantification of DOX in patient samples. As an outstanding feature, the developed probe could detect DOX in unprocessed plasma samples and cell lysates without the requirement for pretreatment.

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy.

Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.

Cancer stem cell-mediated drug resistance: A comprehensive gene expression profile analysis in breast cancer.

Breast cancer is the most frequently diagnosed malignancy in women and a major public health concern. In the current report, differential expression of the breast cancer resistance promoting genes with a focus on breast cancer stem cell related elements as well as the correlation of their mRNAs with various clinicopathologic characteristics, including molecular subtypes, tumor grade/stage, and methylation status, have been investigated using METABRIC and TCGA datasets. To achieve this goal, we downloaded gene expression data of breast cancer patients from TCGA and METABRIC. Then, statistical analyses were used to assess the correlation between the expression levels of stem cell related drug resistant genes and methylation status, tumor grades, various molecular subtypes, and some cancer hallmark gene sets such as immune evasion, metastasis, and angiogenesis. According to the results of this study, a number of stem cell related drug resistant genes are deregulated in breast cancer patients. Furthermore, we observe negative correlations between methylation of resistance genes and mRNA expression. There is a significant difference in the expression of resistance-promoting genes between different molecular subtypes. As mRNA expression and DNA methylation are clearly related, DNA methylation might be a mechanism that regulates these genes in breast cancer cells. As indicated by the differential expression of resistance-promoting genes among various breast cancer molecular subtypes, these genes may function differently in different subtypes of breast cancer. In conclusion, significant deregulation of resistance-promoting factors indicates that these genes may play a significant role in the development of breast cancer.

Chitosan-based nanoscale delivery systems in hepatocellular carcinoma: Versatile bio-platform with theranostic application.

The field of nanomedicine has provided a fresh approach to cancer treatment by addressing the limitations of current therapies and offering new perspectives on enhancing patients' prognoses and chances of survival. Chitosan (CS) is isolated from chitin that has been extensively utilized for surface modification and coating of nanocarriers to improve their biocompatibility, cytotoxicity against tumor cells, and stability. HCC is a prevalent kind of liver tumor that cannot be adequately treated with surgical resection in its advanced stages. Furthermore, the development of resistance to chemotherapy and radiotherapy has caused treatment failure. The targeted delivery of drugs and genes can be mediated by nanostructures in treatment of HCC. The current review focuses on the function of CS-based nanostructures in HCC therapy and discusses the newest advances of nanoparticle-mediated treatment of HCC. Nanostructures based on CS have the capacity to escalate the pharmacokinetic profile of both natural and synthetic drugs, thus improving the effectiveness of HCC therapy. Some experiments have displayed that CS nanoparticles can be deployed to co-deliver drugs to disrupt tumorigenesis in a synergistic way. Moreover, the cationic nature of CS makes it a favorable nanocarrier for delivery of genes and plasmids. The use of CS-based nanostructures can be harnessed for phototherapy. Additionally, the incur poration of ligands including arginylglycylaspartic acid (RGD) into CS can elevate the targeted delivery of drugs to HCC cells. Interestingly, smart CS-based nanostructures, including ROS- and pH-sensitive nanoparticles, have been designed to provide cargo release at the tumor site and enhance the potential for HCC suppression.

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs.

Doxorubicin-loaded micelles in tumor cell-specific chemotherapy.

Nanomedicine is a field that combines biology and engineering to improve disease treatment, particularly in cancer therapy. One of the promising techniques utilized in this area is the use of micelles, which are nanoscale delivery systems that are known for their simple preparation, high biocompatibility, small particle size, and the ability to be functionalized. A commonly employed chemotherapy drug, Doxorubicin (DOX), is an effective inhibitor of topoisomerase II that prevents DNA replication in cancer cells. However, its efficacy is frequently limited by resistance resulting from various factors, including increased activity of drug efflux transporters, heightened oncogenic factors, and lack of targeted delivery. This review aims to highlight the potential of micelles as new nanocarriers for delivering DOX and to examine the challenges involved with employing chemotherapy to treat cancer. Micelles that respond to changes in pH, redox, and light are known as stimuli-responsive micelles, which can improve the targeted delivery of DOX and its cytotoxicity by facilitating its uptake in tumor cells. Additionally, micelles can be utilized to administer a combination of DOX and other drugs and genes to overcome drug resistance mechanisms and improve tumor suppression. Furthermore, micelles can be used in phototherapy, both photodynamic and photothermal, to promote cell death and increase DOX sensitivity in human cancers. Finally, the alteration of micelle surfaces with ligands can further enhance their targeted delivery for cancer suppression.

Gold nanostructure-mediated delivery of anticancer agents: Biomedical applications, reversing drug resistance, and stimuli-responsive nanocarriers.

The application of nanoarchitectures in cancer therapy seems to be beneficial for the delivery of antitumor drugs. In recent years, attempts have been made to reverse drug resistance, one of the factors threatening the lives of cancer patients worldwide. Gold nanoparticles (GNPs) are metal nanostructures with a variety of advantageous properties, such as tunable size and shape, continuous release of chemicals, and simple surface modification. This review focuses on the application of GNPs for the delivery of chemotherapy agents in cancer therapy. Utilizing GNPs results in targeted delivery and increased intracellular accumulation. Besides, GNPs can provide a platform for the co-delivery of anticancer agents and genetic tools with chemotherapeutic compounds to exert a synergistic impact. Furthermore, GNPs can promote oxidative damage and apoptosis by triggering chemosensitivity. Due to their capacity for providing photothermal therapy, GNPs can enhance the cytotoxicity of chemotherapeutic agents against tumor cells. The pH-, redox-, and light-responsive GNPs are beneficial for drug release at the tumor site. For the selective targeting of cancer cells, surface modification of GNPs with ligands has been performed. In addition to improving cytotoxicity, GNPs can prevent the development of drug resistance in tumor cells by facilitating prolonged release and loading low concentrations of chemotherapeutics while maintaining their high antitumor activity. As described in this study, the clinical use of chemotherapeutic drug-loaded GNPs is contingent on enhancing their biocompatibility.