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.

Diagnostic, Therapeutic, and Theranostic Multifunctional Microneedles.

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.

Simple and Rapid Monolayer Self-Assembly of Nanoparticles at the Air/Water Interface.

Colloidal crystals and their two-dimensional (2D) monolayers, which have been commonly applied in nanosphere lithography, have the potential to revolutionize many engineering disciplines; however, current production techniques are hampered by a restricted preparation area, laborious procedures, and the need for advanced equipment. We propose a self-assembly-driven, simple, and low-cost method to prepare 2D colloidal nanosphere monolayers with excellent repeatability across wide regions. The self-assembly capability of colloidal polystyrene (PS) nanospheres at the air/water interface was utilized to transfer the assembled monolayers onto a substrate. This innovative method combines the advantages of methods that permit deposition at the air/water interface, such as Langmuir and drop coating, in order to deliver defect-free, simple-to-install, and simple-to-apply deposition across vast regions. Using field emission scanning electron microscopy and atomic force microscopy, the resultant coatings were characterized. The size of the nanospheres was reduced using an oxygen plasma etch process in an inductively coupled plasma reactive ion etching system, and the reflectance properties of the substrates for various nanosphere sizes were investigated. By evaporation of a thin gold capping layer on the templates, their optical properties were compared using surface-enhanced Raman scattering spectroscopy. This work has the potential to expand the use of nanosphere lithography by offering a simple and reproducible method that eliminates the need for complicated experimental setups and reduces the amount of material required for monolayer coating, thus lowering the cost.

(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.

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.

Eco-friendly chitosan-based nanostructures in diabetes mellitus therapy: Promising bioplatforms with versatile therapeutic perspectives.

Nature-derived polymers, or biopolymers, are among the most employed materials for the development of nanocarriers. Chitosan (CS) is derived from the acetylation of chitin, and this biopolymer displays features such as biocompatibility, biodegradability, low toxicity, and ease of modification. CS-based nano-scale delivery systems have been demonstrated to be promising carriers for drug and gene delivery, and they can provide site-specific delivery of cargo. Owing to the high biocompatibility of CS-based nanocarriers, they can be used in the future in clinical trials. On the other hand, diabetes mellitus (DM) is a chronic disease that can develop due to a lack of insulin secretion or insulin sensitivity. Recently, CS-based nanocarriers have been extensively applied for DM therapy. Oral delivery of insulin is the most common use of CS nanoparticles in DM therapy, and they improve the pharmacological bioavailability of insulin. Moreover, CS-based nanostructures with mucoadhesive features can improve oral bioavailability of insulin. CS-based hydrogels have been developed for the sustained release of drugs and the treatment of DM complications such as wound healing. Furthermore, CS-based nanoparticles can mediate delivery of phytochemicals and other therapeutic agents in DM therapy, and they are promising compounds for the treatment of DM complications, including nephropathy, neuropathy, and cardiovascular diseases, among others. The surface modification of nanostructures with CS can improve their properties in terms of drug delivery and release, biocompatibility, and others, causing high attention to these nanocarriers in DM therapy.

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.

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.

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.

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.

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.

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.

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

Cancer phototherapy has been introduced as 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.

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.

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.

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.

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.