Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology plays a crucial role in the theranostic field due to the functionalization of specific materials that combine tumor detection and targeted treatment features. This review analyzes the clinical impact of nanotechnology, spanning from early-phase trials to pivotal phase 3 studies that have obtained regulatory approval, while also offering a critical perspective on the preclinical domain and its translational potential for future human applications. Despite significant progress, greater attention must be placed on key challenges, such as biocompatibility barriers and the lack of regulatory standardization, to ensure the successful translation of nanomedicine into routine clinical practice.

Cysteine cathepsins have been discovered to be substantially expressed in multiple types of cancer. They play a key role in the progression and growth of these cancers, rendering them appealing targets for nanoscale delivery and noninvasive diagnostic imaging. This review explores cathepsins from the papain-like enzyme family (C1) within the cysteine peptidase clan (CA), emphasizing the role of cathepsin-responsive nanoparticles in tumor growth. Furthermore, it also explores how nanotechnology can harness cathepsin activity to enable targeted drug delivery, improve tumor imaging, and reduce systemic toxicity. By examining the molecular mechanisms governing cathepsin function and evaluating different nanocarrier systems, this work aims to enhance our understanding of targeted cancer treatment. Despite significant advances, challenges remain in translating these nanomedicine platforms into clinical use, including improving delivery efficiency, biocompatibility, long-term safety, and addressing issues such as interspecies protease variability and scalable nanomanufacturing. Future advancement, integrating advanced biomaterials, patient-derived organoid models, bispecific immune-protease targeting, CRISPR-based cathepsin editing, and artificial intelligence-driven pharmacokinetic modeling and analysis will be critical to fully realizing the clinical potential of cathepsin targeted nanomedicines. These innovations hold promises for advancing precision oncology by overcoming current limitations and improving patient outcomes.

The tumor microenvironment (TME) has a major role in malignancy and its complex nature can mediate tumor survival, metastasis, immune evasion, and drug resistance. Thus, reprogramming or regulating the immunosuppressive TME has a significant contribution to make in cancer therapy. Targeting TME with nanocarriers (NCs) has been widely used to directly deliver anticancer drugs to control TME, which has revealed auspicious outcomes. TME can be reprogrammed by using a range of NCs to regulate immunosuppressive factors and activate immunostimulatory cells. Moreover, TME can be ameliorated via regulating the redox environment, oxygen content, and pH value of the tumor site. NCs have the capacity to provide site-specific delivery of therapeutic agents, controlled release, enhanced solubility and stability, decreased toxicities, and enhanced pharmacokinetics as well as biodistribution. Numerous NCs have demonstrated their potential by inducing distinct anticancer mechanisms by delivering a range of anticancer drugs in various preclinical studies, including metal NCs, liposomal NCs, solid lipid NCs, micelles, nanoemulsions, polymer-based NCs, dendrimers, nanoclays, nanocrystals, and many more. Some of them have already received US Food and Drug Administration approval, and some have entered different clinical phases. However, there are several challenges in NC-mediated TME targeting, including scale-up of NC-based cancer therapy, rapid clearance of NCs by the mononuclear phagocyte system, and TME heterogeneity. In order to harness the full potential of NCs in tumor treatment, there are several factors that need to be carefully studied, including optimization of drug loading into NCs, NC-associated immunogenicity, and biocompatibility for the successful translation of NC-based anticancer therapies into clinical practice. In this review, a range of NCs and their applications in drug delivery to remodel TME for cancer therapy are extensively discussed. Moreover, findings from numerous preclinical and clinical studies with these NCs are also highlighted.

Dextran-thioketal conjugate (DTKC) nanocarrier responsive to endogenous as well as exogenous stimuli is developed for delivering hydrophilic payloads. First, water-soluble reactive oxygen species (ROS)-responsive DTKCs are synthesized and responsiveness to various ROS stimuli is studied. Next, different DTKC nanocarriers (NCs) loaded with the respective hydrophilic molecules - fluorescent dye (rhodamine B, RhoB), photosensitizer, PS (rose bengal, RB), and chemotherapeutic drug (doxorubicin hydrochloride, Dox) - are synthesized using inverse miniemulsion interfacial polymerization. All NCs exhibit nanocapsule morphology, and cargo dependent hydrodynamic diameters (166-194 nm) in water, an encapsulation efficiency between 79 and 91 %, and a drug loading content of about 11 %. RhoB-NCs and Dox-NCs exhibit time-dependent release upon exposure to different H2O2 concentrations and an enhanced release in conditioned medium collected from oral squamous cell carcinoma (OSCC) cells. Further, as a proof-of-concept, light-responsive payload release from PS loaded NCs via a cascade reaction is confirmed. The in vitro studies show that RhoB-NCs and RB-NCs are biocompatible while the Dox-NCs exhibit cytotoxic effects. Such dextran-based ROS-responsive NCs sensitive to endogenous (ROS rich environment) as well as exogenous (light in combination with a PS) stimuli are highly interesting to realize combination therapies, for instance combining a chemotherapeutic drug and a photosensitizer for application in photochemotherapy.

Nanomedicine has significantly advanced the treatment of various cancer phenotypes, addressing numerous challenges associated with conventional therapies. Researchers have extensively investigated the physicochemical properties of nanocarriers, such as charge, morphology, and surface chemistry, to optimize drug delivery systems. In the context of transformable nanomedicine, these properties are particularly critical for overcoming existing limitations, including suboptimal blood circulation times, sequestration by the reticuloendothelial system and mononuclear phagocyte system, and inefficient targeting of the tumor microenvironment (TME). Alterations in nanocarrier geometry, surface charge, and hydrophilicity have shown potential in mitigating these barriers, offering improved therapeutic outcomes and enhanced biomedical applications. This review explores controlled modulation of these properties in the context of anticancer therapy, offering an in-depth exploration of transformable strategies activated by both internal and external stimuli. We analyze the implications of these tunable characteristics on pharmacokinetics, biodistribution, and targeted delivery to the TME. Additionally, we address the current challenges in the clinical translation of these advanced nanocarriers and propose strategies to overcome these obstacles to enhance the clinical feasibility of nanomedicine-based cancer therapies.

Diabetes is a medical condition that belongs to the group of chronic diseases that affect how the body processes glucose, the primary source of energy for cells. Glucose comes indirectly from the consumed food and is carried by bloodstream to various cells in the body. Insulin, a hormone synthesized by the pancreas plays a vital role in the conversion of glucose to energy. Managing diabetes involves regular monitoring of blood sugar levels, adopting a healthy diet, engaging in regular physical activity, and taking medications or insulin as prescribed by a healthcare provider. Proper management of diabetes may lead to the prevention or delay of diabetic complications may further sever other diseases associated impediment. Drug delivery in the management of diabetes is designed to administer insulin or other diabetes medications in a controlled and convenient manner. Recently nanotechnology has emerged as a transformative approach in the management of diabetic complications, particularly through carrier-mediated nano-biomedicine. Several natural products have been studied and reported for their potential role in managing diabetes. While they may not replace standard medical treatments, some of these natural products could complement existing therapies and support overall diabetes management. Therefore, this review explores the potential of nanocarriers to enhance drug delivery systems for diabetes mellitus treatment, addressing the limitations of conventional therapies that often suffer from poor bioavailability and frequent dosing requirements. Studies have demonstrated that bridging these bioactive compounds significantly enhance the therapeutic efficacy in the management of diabetes. Challenges remain in translating these technologies from laboratory settings to clinical applications; however, the potential benefits for improving glycemic control and overall quality of life for diabetic patients are substantial. Future research should focus on optimizing these nano-biomedicine strategies to realize their full therapeutic potential in diabetes management.

Lenvatinib, endorse as a first-line targeted therapy, has demonstrated efficacy in extending the survival span of individuals afflicted with advanced Hepatocellular carcinoma (HCC). However, its therapeutic effect wears off with time, which is ascribed to the cancer cell's tendency to evade and tamper with its usual modes of action, severely limiting its clinical use. This study devises an innovative therapeutic modality involving the synergistic co-delivery of FePt nanoparticles (NPs) and Lenvatinib via poly lactic-co-glycolic acid (PLGA) NPs encase in HCC cell membranes (Len/FePt@CMP NPs). The investigation explores the mechanism through which Lenvatinib induces ferroptosis in HCC, notably by dampening the glutathione peroxidase 4 (GPX4) through the inhibition of fibroblast growth factor receptor 4. FePt NPs are engineered to enhance the efficacy of ferroptosis and apoptosis for HCC treatment. Concurrently, the incorporation of the cancer cell membrane facilitates the targeted accumulation of NPs at the tumor site, leveraging mechanisms of immune evasion and homologous targeting. This enhances ferroptosis/apoptosis treatment efficacy, triggeres by Len/FePt@CMP NPs, is convincingly demonstrated both in vitro and in vivo. The proposed approach has the potential to redefine HCC therapeutic paradigms by overcoming mono-therapeutic limitations in current clinical treatments, showcasing the improved efficacy of a comprehensive strategy.

Evodiamine (EVO), a natural bioactive compound extracted from Evodia rutaecarpa, shows therapeutic ability against malignant melanoma. However, the poor solubility and bioavailability of EVO limit its clinical application. Metal-organic frameworks (MOFs) have shown excellent physical and chemical properties and are widely used as drug delivery systems. Among them, zeolitic imidazolate framework-8 (ZIF-8) is a research popular material because of its unique properties, such as hydrothermal stability, non-toxicity, biocompatibility, and pH sensitivity. In this study, in order to load EVO, a drug carrier that hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) is synthesized. This drug carrier has shown drug loading with 6.2 ± 0.6%, and the nano drugs (EVO@ZIF-8/HA) have good dispersibility. Owing to the decoration HA of EVO@ZIF-8, the potential of the nano drugs is reversed from the positive charge to the negative charge, which is beneficial to blood circulation in vivo. Furthermore, because the CD44-expressing in tumor cells is excessed, the endocytosis and accumulation of nano drugs in tumor cells are beneficial to improvement. Compared with free EVO, EVO@ZIF-8/HA has shown a significantly improved anti-tumor efficacy in vitro and in vivo. In summary, the drug carrier effectively addresses the challenges that are caused by the strong hydrophobicity and low bioavailability of EVO, thereby targeted tumor therapy of EVO can be achieved.

Cancer, ranking just below cardiovascular diseases, is a leading cause of mortality worldwide. The key to enhancing survival rates among cancer patients lies in the early detection, removal, and treatment of tumors. However, the broad-spectrum nature of current treatments, including chemotherapy and radiation therapy, results in significant collateral damage to healthy cells and tissues. In this context, hyperbranched polymers present a promising avenue for more targeted therapy. These polymers can be loaded with chemotherapeutic drugs and modified with specific ligands to selectively target cancer cells via glucose transporters, which are overexpressed in many cancer types. To enhance the delivery of drugs to cancer cells, we have engineered an N-acetyl glucosamine conjugated version of this polymer. The characterization of these nanocarriers was evaluated using various techniques, including 1H NMR, dynamic light scattering, and FTIR spectroscopy. Additionally, confocal microscopy was utilized to compare the accumulation of doxorubicin in cancer cells using both the N-acetyl glucosamine-conjugated and unmodified versions of H40 Boltorn™. Our observations indicated a superior accumulation of doxorubicin in cells treated with the modified H40 polymer. Further evaluation of the drug-loaded nanocarriers was conducted on MDA-MB-231 and 4T1 breast cancer cell lines, focusing on their cytotoxic effects. This suggests that the targeted delivery of anticancer drugs using the modified H40 Boltorn™ nanocarriers significantly enhances the ability to kill breast cancer cells, offering a more efficient and selective approach to chemotherapy that minimizes impact on healthy tissues and cells.

Cancer is the deadliest and most serious health problem. The mortality rate of cancer patients has increased significantly worldwide in recent years. There are several treatments available, but these treatments have many limitations, such as non-specific targeting, toxicity, bioavailability, solubility, permeability problems, serious side effects, and a higher dose. Many people prefer phytomedicine because it has fewer side effects. However, amygdalin is a naturally occurring phytoconstituent. It has many harmful effects due to the cyanide group present in the chemical structure. Many scientists and researchers have given their thoughts associated with amygdalin and its toxicities. However, there is a need for a more advanced, effective, and newer delivery system with reduced toxicity effects of amygdalin. Nanotechnology has become a more refined and emerging medical approach, offering innovative research areas to treat cancer. This review focuses on the use of amygdaline as herbal medicine encapsulating into several nanoparticulate delivery systems such as silver nanoparticles, graphene oxide nanoparticles, gold nanoparticles, nanofibers, nanocomposites, niosomes, and magnetic nanoparticles in the treatment of cancer. In addition, this article provides information on amygdalin structure and physical properties, pharmacokinetics, toxicity, and challenges with amygdalin.

Myeloid leukemia is a stem cell disease with high mortality due to the challenges of high-dose treatments and side effects. Innovative nanoparticle drug delivery systems are being explored to enhance efficacy and tissue-targeted therapy. This study investigates the potential of Bentonite (BNT)-based nanoparticles (NPs) as drug carriers for azacitidine (AZA) in treating THP-1 and K562 myeloid leukemia (AML) cell lines, aiming to improve drug stability, bioavailability, and therapeutic efficacy while ensuring controlled release.

Bentonite clay morphology was analyzed using Scanning Electron Microscopes. The BNT-AZA combination was tested in THP-1 and K562 cell cultures via in vitro proliferation tests, CCK-8 assays, and drug release tests with dialysis membranes. Apoptosis and internalization were evaluated using Annexin V-FITC and fluorescence methods, respectively.

The BNT-AZA exhibited controlled release over 8 hours, with 50% released within 2 hours, 90% by the 4th hour, and prolonged release beyond 8 hours. This profile reduces side effects while increasing efficacy in target cells. Bentonite demonstrated significant drug-loading capacity, controlled release, and tumor-targeting capabilities. At concentrations of 10, 25, 50, and 100 µg/mL, BNT showed dose-dependent antiproliferative effects, maintaining low cytotoxicity at lower concentrations. The combination of azacytidine and bentonite exhibited a synergistic effect in inhibiting cell proliferation, with significant decreases in cell viability in the 1 µM azacytidine + 10 µg/mL bentonite, 5 µM azacytidine + 10 µg/mL bentonite, and 10 µM azacytidine + 10 µg/mL bentonite groups compared to the controls. The combination of 1 µM AZA with 10 µg/mL BNT achieved similar efficacy to 10 µM AZA alone, suggesting a potential for dose reduction and improved safety.

BNT nanoparticles are promising carriers for AZA, enhancing targeted delivery, reducing side effects, and potentially lowering the required dose for leukemia treatment. These findings support further investigation into the clinical application of BNT-AZA in hematologic cancers.

Surgery and chemoradiotherapy are the main clinical treatment methods for colorectal cancer (CRC), but the prognosis is poor. The emergence of nanomedicine brings bright light to the treatment of CRC. However, there has not been a comprehensive and systematic analysis of CRC and nanomedicine by bibliometrics.

We searched the Web of Science Core Collection database (WOSCC) for relevant literature published from 2011 to 2024. We used VOSviewer and Citespace to analyze countries, institutions, authors, keywords, highly cited references, and co-cited references.

3105 pieces of literatures were included in the research analysis, and PEOPLES R CHINA and the USA took the leading position in the number of papers published and had academic influence. The Chinese Academy of Sciences posted the most papers. The most prolific scholar was Abnous Khalil. The level of economic development is inversely proportional to the number of cases and deaths of colorectal cancer. Nanoparticles (NPs), the nanomedical drug delivery system (NDDS) is a hot topic in the field. Photodynamic therapy (PDT), immunogenic cell death (ICD), tumor microenvironment (TEM), folic acid, and pH are the cutting edge of the field.

This paper introduces the research hotspot, emphasis, and frontier of CRC and nanomedicine, and points out the direction for this field.

Aim: We conducted a bibliometric analysis to quantitatively study the development pathway, research hotspots and evolutionary trends of nano-drug delivery systems (NDDS) in treating urological tumors.Materials & methods: We used the Web of Science Core Collection to retrieve the literature related to NDDS in the urological tumors up to November 1, 2023. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer and R-Bibliometrix. The major aspects of analysis included contributions from different countries/regions, authors' contributions, keywords identification, citation frequencies and overall research trends.Results: We included 3,220 articles. The analysis of annual publication trends revealed significant growth in this field since 2010, which has continued to the present day. The United States and China have far exceeded other countries/regions in the publication volume of papers in this field. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Mucoadhesive NDDS for intravesical drug delivery is a hotspot and a potential research material for bladder cancer.Conclusion: The field of NDDS in urological tumors has emerged as a research hotspot. Future research should focus on synergistic effects of NDDS with other treatment modalities.

This comprehensive review provides an in-depth analysis of how nanotechnology has revolutionized cancer theragnostic, which combines diagnostic and therapeutic methods to customize cancer treatment. The study examines the unique attributes, uses, and difficulties linked to different types of nanoparticles, including gold, iron oxide, silica, Quantum dots, Carbon nanotubes, and liposomes, in the context of cancer treatment. In addition, the paper examines the progression of nanotheranostics, emphasizing its uses in precise medication administration, photothermal therapy, and sophisticated diagnostic methods such as MRI, CT, and fluorescence imaging. Moreover, the article highlights the capacity of nanoparticles to improve the effectiveness of drugs, reduce the overall toxicity in the body, and open up new possibilities for treating cancer by releasing drugs in a controlled manner and targeting specific areas. Furthermore, it tackles concerns regarding the compatibility of nanoparticles and their potential harmful effects, emphasizing the significance of continuous study to improve nanotherapeutic methods for use in medical treatments. The review finishes by outlining potential future applications of nanotechnology in predictive oncology and customized medicine.

Stimuli-responsive polymeric micelles have emerged as a revolutionary approach for enhancing the in vivo stability, biocompatibility, and targeted delivery of functional nanoparticles (FNPs) in biomedicine. This article comprehensively reviews the preparation methods of these polymer micelles, detailing the innovative strategies employed to introduce stimulus responsiveness and surface modifications essential for precise targeting. We delve into the breakthroughs in utilizing these micelles to selectively deliver various FNPs including magnetic nanoparticles, upconversion nanoparticles, gold nanoparticles, and quantum dots, highlighting their transformative impact in the biomedical realm. Concluding, we present an insight into the current research landscape, addressing the challenges at hand, and envisioning the future trajectory in this burgeoning domain. Join us as we navigate the exciting confluence of polymer science and nanotechnology in reshaping biomedical solutions.

Glioma is the most common intracranial malignant tumor, with severe difficulty in treatment and a low patient survival rate. Due to the heterogeneity and invasiveness of tumors, lack of personalized clinical treatment design, and physiological barriers, it is often difficult to accurately distinguish gliomas, which dramatically affects the subsequent diagnosis, imaging treatment, and prognosis. Fortunately, nano-delivery systems have demonstrated unprecedented capabilities in diagnosing and treating gliomas in recent years. They have been modified and surface modified to efficiently traverse BBB/BBTB, target lesion sites, and intelligently release therapeutic or contrast agents, thereby achieving precise imaging and treatment. In this review, we focus on nano-delivery systems. Firstly, we provide an overview of the standard and emerging diagnostic and treatment technologies for glioma in clinical practice. After induction and analysis, we focus on summarizing the delivery methods of drug delivery systems, the design of nanoparticles, and their new advances in glioma imaging and treatment in recent years. Finally, we discussed the prospects and potential challenges of drug-delivery systems in diagnosing and treating glioma.

Ischemic stroke is a complex, high-mortality disease with multifactorial etiology and pathogenesis. Currently, drug therapy is mainly used treat ischemic stroke in clinic, but there are still some limitations, such as limited blood-brain barrier (BBB) penetration efficiency, a narrow treatment time window and drug side effects. Recent studies have pointed out that drug delivery systems based on polymeric nanocarriers can effectively improve the insufficient treatment for ischemic stroke. They can provide neuronal protection by extending the plasma half-life of drugs, enhancing the drug's permeability to penetrate the BBB, and targeting specific structures and cells. In this review, we classified polymeric nanocarriers used for delivering ischemic stroke drugs and introduced their preparation methods. We also evaluated the feasibility and effectiveness and discussed the existing limitations and prospects of polymeric nanocarriers for ischemic stroke treatment. We hoped that this review could provide a theoretical basis for the future development of nanomedicine delivery systems for the treatment of ischemic stroke.

Despite ongoing advances in cancer therapy, the results for the treatment of breast cancer are not satisfactory. The advent of nanotechnology promises to be an essential tool to improve drug delivery effectiveness in cancer therapy. Nanotechnology provides an opportunity to enhance the treatment modality by preventing degradation, improving tumour targeting, and controlling drug release. Recent advances have revealed several strategies to prevent cancer metastasis using nano-drug delivery systems (NDDS). These strategies include the design of appropriate nanocarriers loaded with anti-cancer drugs that target the optimization of physicochemical properties, modulate the tumour microenvironment, and target biomimetic techniques. Nanocarriers have emerged as a preferential approach in the chemotropic treatment for breast cancer due to their pivotal role in safeguarding the therapeutic agents against degradation. They facilitate efficient drug concentration in targeted cells, surmount the resistance of drugs, and possess a small size. Nevertheless, these nanocarrier(s) have some limitations, such as less permeability across the barrier and low bioavailability of loaded drugs. To overcome these challenges, integrating external stimuli has been employed, encompassing infrared light, thermal stimulation, microwaves, and X-rays. Among these stimuli, ultrasound-triggered nanocarriers have gained significant attention due to their cost-effectiveness, non-invasive nature, specificity, ability to penetrate tissues, and capacity to deliver elevated drug concentrations to intended targets. This article comprehensively reviews recent advancements in different nanocarriers for breast cancer chemotherapy. It also delves into the associated hurdles and offers valuable insights into the prospective directions for this innovative field.

Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities.

This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials.

Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers.

Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.

In this study, we developed self-assembling nanoparticles (LCPs) able to trigger the release of Chlorambucil (Chl) and Doxorubicin (DOX) to MDA-MB-231 cells by exploiting the enzyme and redox signals. The DOX loaded LCPs was prepared by the self-assembly of two chondroitin sulphate (CS) derivatives, obtained by the covalent conjugation of Lipoic Acid (LA) and Chlorambucil (Chl) to the CS backbone. After the physic-chemical characterization of the conjugates by FT-IR, 1H NMR, and determination of the critical aggregation concentration, spherical nanoparticles with mean hydrodynamic diameter of 45 nm (P.D.I. 0.24) and Z-potential of - 44 mV were obtained by water addition/solvent evaporation method. In vitro experiments for the release of Chl and DOX were performed in healthy and cancer cells, using a cell culture media to maintain the physiological intracellular conditions (pH 7.4) (and concentration of esterase and GSH. The results allowed the selective release of the payloads to be detected: Chl release of 0 and 41% were obtained after 2 h incubation in normal and in cancer cells respectively, while values of 35 (in healthy cells) and 60% (in cancer cells) were recorded for DOX release after 96 h. Finally, viability studies proved the ability of the newly proposed nanosystem to enhance the cytotoxic activity of the two drugs against cancer cells.

Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.

Pancreatic cancer is one of the major cause of cancer-related deaths worldwide, and is mainly associated with carcinomas of the pancreatic tissue. Current therapies for treating pancreatic cancer have a major drawback related to their low bioavailability and non-specificity, which leads to low therapeutic efficacy and side effects. Luteolin (LUT) has been clinically used for treatment of various types of cancer, although its clinical use has declined owing to its low oral bioavailability. In this work, we prepared an effervescent-based nanocarrier (NG) that rapidly triggers an effervescent reaction and transforms into nanomicelles to modulate the oral bioavailability of the hydrophobic drug Luteolin (LUT). Furthermore, we performed tests to assess its in vitro epithelial cell permeability and cellular internalization on a Caco-2 monolayer. We also performed in vivo toxicity assessment using animal models. Further, we evaluated the nanocarrier system's in vivo efficacy in tumor xenograft pancreatic cancer models. We validated that being pH responsive, our effervescent carrier disassembles at intestinal pH and is absorbed through the intestinal lymphatic system (ILS) to further site-specifically invade the pancreatic cancer cells. Furthermore, the negative surface charge and particle size (450 ± 100 nm) of the nanomicelles helped to internalize LUT through the ILS. We observed that LUT-loaded nanomicelles have significant antipancreatic cancer efficacy by activating caspase-3 activity and downregulating VEGF-A, FAK, TNF-α, and Ki-67. Unlike other drug-delivery systems, we developed noninvasive nanocarrier system has the capability of transporting the hydrophobic drug LUT from the intestine to the tumor site by utilizing the ILS.

Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.

Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.

Stimuli responsive delivery systems, also known as smart/intelligent drug delivery systems, are specialized delivery vehicles designed to provide spatiotemporal control over drug release at target sites in various diseased conditions, including tumor, inflammation and many others. Recent advances in the design and development of a wide variety of stimuli-responsive (pH, redox, enzyme, temperature) materials have resulted in their widespread use in drug delivery and tissue engineering. The aim of this review is to provide an insight of recent nanoparticulate drug delivery systems including polymeric nanoparticles, dendrimers, lipid-based nanoparticles and the design of new polymer-drug conjugates (PDCs), with a major emphasis on natural along with synthetic commercial polymers used in their construction. Special focus has been placed on stimuli-responsive polymeric materials, their preparation methods, and the design of novel single and multiple stimuli-responsive materials that can provide controlled drug release in response a specific stimulus. These stimuli-sensitive drug nanoparticulate systems have exhibited varying degrees of substitution with enhanced in vitro/in vivo release. However, in an attempt to further increase drug release, new dual and multi-stimuli based natural polymeric nanocarriers have been investigated which respond to a mixture of two or more signals and are awaiting clinical trials. The translation of biopolymeric directed stimuli-sensitive drug delivery systems in clinic demands a thorough knowledge of its mechanism and drug release pattern in order to produce affordable and patient friendly products.

Ferroptosis has received increasing attention as a novel nonapoptotic programmed death. Recently, iron-based nanomaterials have been extensively exploited for efficient tumor ferroptosis therapy, as they directly release high concentrations of iron and increase intracellular reactive oxygen species levels. Breast cancer is one of the commonest malignant tumors in women; inhibiting breast cancer cell proliferation through activating the ferroptosis pathway could be a potential new target for patient treatment. Here, we briefly introduce the background of ferroptosis and systematically review the current cancer therapeutic strategies based on iron-based ferroptosis inducers. Finally, we summarize the advantages of these various ferroptosis inducers and shed light on future perspectives. This review aims to provide better guidance for the development of iron-based nanomaterial ferroptosis inducers.

Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in 20-30% of breast cancer tumors (HER2-positive breast cancers) and is associated with more aggressive onset of disease, higher recurrence rate and increased mortality. Monoclonal antibodies (mAb) like trastuzumab and pertuzumab in combination with chemotherapeutics, and trastuzumab-based antibody drug conjugates (ADCs) are used in the clinic to treat these cancers. An alternative targeted strategy (not yet in clinical use) is the encapsulation of chemotherapeutic drugs in immunoliposomes. Such systems may not only facilitate targeted delivery to the tumor and improve intracellular penetration, but also override some of the resistance developed by tumors in response to cytotoxic loads. As a supplement to classical chemotherapeutics (based on organic compounds and conventional platinum-based derivatives), gold compounds are emerging as potential anticancer agents due to their high cytotoxicity and capacity for immunogenic cell death. Here, we describe the development of immunoliposomes functionalized with trastuzumab and pertuzumab; containing simple gold(i) neutral compounds ([AuCl(PR3)] (PR3 = PPh3 (1), PEt3 (2))) generated by the thin-film method to afford Lipo-1-Lipo-2. Trastuzumab and pertuzumab were engrafted onto these liposomes to generate gold-based immunoliposomes (Immunolipo-Tras-1, Immunolipo-Tras-2, Immunolipo-Per-1, Immunolipo-Per-2). We have characterized all liposomal formulations and demonstrated that the immunoliposomes (190 nm) are stable, have high binding affinity for HER2, and display selective cytotoxicity towards HER2-positive breast cancer cell lines. Trastuzumab-based immunoliposomes of a smaller size (100 nm) - encapsulating [AuCl(PEt3)] (2) - have been generated by an extrusion homogenization method. These optimized immunoliposomes (Opt-Immunolipo-Tras-2) have a trastuzumab engraftment efficiency, encapsulation efficiency for 2, and affinity for HER-2 similar to the immunoliposomes obtained by sonication (Immunolipo-Tras-2). While the amount of Au encapsulated is slightly lower, they display almost identical cytotoxicity and selectivity profiles. Moreover, the fluorescently-labeled phosphane drug [AuCl(PPh2-BODIPY)] (3) was encapsulated in both larger (Immunolipo-Tras-3) and smaller (Opt-Immunolipo-Tras-3) immunoliposomes and used to visualize the intracellular localization of the payload. Fluorescent imaging studies found that Opt-Immunolipo-Tras-3 accumulates in the cells more than 3 and that the unencapsulated payload accumulates primarily in lysosomes, while targeted liposomal 3 localizes in mitochondria and ER, hinting at different possibilities for modes of action.

The quest for safe chemotherapy has attracted researchers to explore anticancer potential of herbal medicines. Owing to upsurging evidence of herbal drug's beneficial effects, hopes are restored for augmenting survival rates in cancer patients. However, phytoconstituents confronted severe limitations in terms of poor absorption, low-stability, and low bioavailability. Along with toxicity issues associated with phytoconstituents, quality control and limited regulatory guidance also hinder the prevalence of herbal medicines for cancer therapy. Attempts are underway to exploit nanocarriers to circumvent the limitations of existing and new herbal drugs, where biological macromolecules (e.g., chitosan, hyaluronic acid, etc.) are established highly effective in fabricating nanocarriers and cancer targeting. Among the discussed nanocarriers, liposomes and micelles possess properties to cargo hydro- and lipophilic herbal constituents with surface modification for targeted delivery. Majorly, PEG, transferrin and folate are utilized for surface modification to improve bioavailability, circulation time and targetability. The dendrimer and carbon nanotubes responded in high-loading efficiency of phytoconstituent; whereas, SLN and nanoemulsions are suited carriers for lipophilic extracts. This review emphasized unveiling the latent potential of herbal drugs along with discussing on extended benefits of nanocarriers-based delivery of phytoconstituents for safe cancer therapy owing to enhanced clinical and preclinical outcomes without compromising safety.

Colon cancer is emerging as one of the most common cancers worldwide, ranking in the top three in morbidity and mortality. Oral methotrexate (MTX) has been employed as a first-line treatment for various cancers, such as colon, breast, and lung cancer. However, the complexity and particularity of the gastrointestinal microenvironment and the limitations of MTX itself, including severe adverse effects and instability, are the main obstacles to the safe delivery of MTX to colon tumor sites. Herein, an innovative oral administrated anticancer therapeutic MTX@Am7CD/SDS NPs equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release intestinal drug under mild conditions. In cellular assays, compared with free MTX, MTX@Am7CD/SDS NPs showed a favorable tumor inhibition effect on three tumor cell lines, as well as excellent cell uptake and apoptosis-inducing effect on SW480 cells. Therefore, this work provides a feasible solution for the safe use of MTX in the treatment of colon cancer and even other intestinal diseases.

Bioorthogonal catalysis, a class of catalytic reactions that are mediated by abiotic metals and proceed in biological environments without interfering with native biochemical reactions, has gained ever-increasing momentum in prodrug delivery over the past few decades. Albeit great progress has been attained in developing new bioorthogonal catalytic reactions and optimizing the catalytic performance of transition metal catalysts (TMCs), the use of TMCs to activate chemotherapeutics at the site of interest in vivo remains a challenging endeavor. To translate the bioorthogonal catalysis-mediated prodrug activation paradigm from flasks to animals, TMCs with targeting capability and stimulus-responsive behavior have been well-designed to perform chemical transformations in a controlled manner within highly complex biochemical systems, rendering on-demand drug activation to mitigate off-target toxicity. Here, we review the recent advances in the development of controllable bioorthogonal catalysis systems, with an emphasis on different strategies for engineering TMCs to achieve precise control over prodrug activation. Furthermore, we outline the envisaged challenges and discuss future directions of controllable bioorthogonal catalysis for disease therapy.

Prostate cancer (PCa) is a prevalent malignancy with increasing incidence in middle-aged and older men. Despite various treatment options, advanced metastatic PCa remains challenging with poor prognosis and limited effective therapies. Nanomedicine, with its targeted drug delivery capabilities, has emerged as a promising approach to enhance treatment efficacy and reduce adverse effects. Prostate-specific membrane antigen (PSMA) stands as one of the most distinctive and highly selective biomarkers for PCa, exhibiting robust expression in PCa cells. In this review, we explore the applications of PSMA-targeted nanomedicines in advanced PCa management. Our primary objective is to bridge the gap between cutting-edge nanomedicine research and clinical practice, making it accessible to the medical community. We discuss mainstream treatment strategies for advanced PCa, including chemotherapy, radiotherapy, and immunotherapy, in the context of PSMA-targeted nanomedicines. Additionally, we elucidate novel treatment concepts such as photodynamic and photothermal therapies, along with nano-theragnostics. We present the content in a clear and accessible manner, appealing to general physicians, including those with limited backgrounds in biochemistry and bioengineering. The review emphasizes the potential benefits of PSMA-targeted nanomedicines in enhancing treatment efficiency and improving patient outcomes. While the use of PSMA-targeted nano-drug delivery has demonstrated promising results, further investigation is required to comprehend the precise mechanisms of action, pharmacotoxicity, and long-term outcomes. By meticulous optimization of the combination of nanomedicines and PSMA ligands, a novel horizon of PSMA-targeted nanomedicine-based combination therapy could bring renewed hope for patients with advanced PCa.

Background: Colorectal cancer (CRC) is a prevalent malignancy affecting the digestive tract, and its incidence has been steadily rising over the years. Surgery remains the primary treatment modality for advanced colorectal cancer, complemented by chemotherapy. The development of drug resistance to chemotherapy is a significant contributor to treatment failure in colorectal cancer. Nanodrug delivery systems (NDDS) can significantly improve the delivery and efficacy of antitumor drugs in multiple ways. However, there is a lack of visualization of NDDS research structures and research hotspots in the field of colorectal cancer, and the elaboration of potential research areas remains to be discovered. Objective: To comprehensively explore the current research status and development trend of NDDS in CRC research. Methods: Bibliometric analysis of articles and reviews on NDDS for CRC published between 2002 and 2022 using tools including CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel was performed. Results: A total of 1866 publications authored by 9,870 individuals affiliated with 6,126 institutions across 293 countries/regions were included in the analysis. These publications appeared in 456 journals. Abnous Khalil has the highest number of publications in this field. The most published journals are the International Journal of Nanomedicine, International Journal of Pharmaceutics, and Biomaterials. Notably, the Journal of Controlled Release has the highest citation count and the third-highest H-index. Thematic analysis identified "inflammatory bowel disease"," "oral drug delivery," and "ulcerative colitis" as areas requiring further development. Keyword analysis revealed that "ulcerative colitis," "exosomes," and "as1411"have emerged as keywords within the last 2 years. These emerging keywords may become the focal points of future research. Conclusion: Our findings reveal the current research landscape and intellectual structure of NDDS in CRC research which helps researchers understand the research trends and hot spots in this field.

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.

Reactive oxygen species (ROS)-sensitive polymer nanoparticles were synthesized for tumor targeting of an anticancer drug, doxorubicin (DOX). For this purpose, chitosan-methoxy poly(ethylene glycol) (mPEG) (ChitoPEG)-graft copolymer was synthesized and then DOX was conjugated to the backbone of chitosan using a thioketal linker. Subsequently, the chemical structure of the DOX-conjugated ChitoPEG copolymer (ChitoPEGthDOX) was confirmed via 1H nuclear magnetic resonance (NMR) spectra. Nanoparticles of the ChitoPEGthDOX conjugates have spherical shapes and a size of approximately 100 nm. Transmission electron microscopy (TEM) has shown that ChitoPEGthDOX nanoparticles disintegrate in the presence of hydrogen peroxide and the particle size distribution also changes from a monomodal/narrow distribution pattern to a multi-modal/wide distribution pattern. Furthermore, DOX is released faster in the presence of hydrogen peroxide. These results indicated that ChitoPEGthDOX nanoparticles have ROS sensitivity. The anticancer activity of the nanoparticles was evaluated using AT84 oral squamous carcinoma cells. Moreover, DOX-resistant AT84 cells were prepared in vitro. DOX and its nanoparticles showed dose-dependent cytotoxicity in both DOX-sensitive and DOX-resistant AT84 cells in vitro. However, DOX itself showed reduced cytotoxicity against DOX-resistant AT84 cells, while the nanoparticles showed almost similar cytotoxicity to DOX-sensitive and DOX-resistant AT84 cells. This result may be due to the inhibition of intracellular delivery of free DOX, while nanoparticles were efficiently internalized in DOX-resistant cells. The in vivo study of a DOX-resistant AT84 cell-bearing tumor xenograft model showed that nanoparticles have higher antitumor efficacy than those found in free DOX treatment. These results may be related to the efficient accumulation of nanoparticles in the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was stronger than that of any other organs. Our findings suggest that ChitoPEGthDOX nanoparticles may be a promising candidate for ROS-sensitive anticancer delivery against DOX-resistant oral cancer cells.

The metabolism in eukaryotic cells is a highly ordered system involving various cellular compartments, which fluctuates based on physiological rhythms. Organelles, as the smallest independent sub-cell unit, are important contributors to cell metabolism and drug metabolism, collectively designated intracellular metabolism. However, disruption of intracellular spatiotemporal metabolism can lead to disease development and progression, as well as drug treatment interference. In this review, we systematically discuss spatiotemporal metabolism in cells and cell subpopulations. In particular, we focused on metabolism compartmentalization and physiological rhythms, including the variation and regulation of metabolic enzymes, metabolic pathways, and metabolites. Additionally, the intricate relationship among intracellular spatiotemporal metabolism, metabolism-related diseases, and drug therapy/toxicity has been discussed. Finally, approaches and strategies for intracellular spatiotemporal metabolism analysis and potential target identification are introduced, along with examples of potential new drug design based on this.

Bone tumors are relatively rare, which are complex cancers and mostly involve the long bones and pelvis. Bone cancer is mainly categorized into osteosarcoma (OS), chondrosarcoma, and Ewing sarcoma. Of these, OS is the most intimidating cancer of the bone tissue, which is mostly found in the log bones in young children and older adults. Conspicuously, the current chemotherapy modalities used for the treatment of OS often fail mainly due to (i) the non-specific detrimental effects on normal healthy cells/tissues, (ii) the possible emergence of drug resistance mechanisms by cancer cells, and (iii) difficulty in the efficient delivery of anticancer drugs to the target cells. To impose the maximal therapeutic impacts on cancerous cells, it is of paramount necessity to specifically deliver chemotherapeutic agents to the tumor site and target the diseased cells using advanced nanoscale multifunctional drug delivery systems (DDSs) developed using organic and inorganic nanosystems. In this review, we provide deep insights into the development of various DDSs applied in targeting and eradicating OS. We elaborate on different DDSs developed using biomaterials, including chitosan, collagen, poly(lactic acid), poly(lactic-co-glycolic acid), polycaprolactone, poly(ethylene glycol), polyvinyl alcohol, polyethyleneimine, quantum dots, polypeptide, lipid NPs, and exosomes. We also discuss DDSs established using inorganic nanoscale materials such as magnetic NPs, gold, zinc, titanium NPs, ceramic materials, silica, silver NPs, and platinum NPs. We further highlight anticancer drugs' role in bone cancer therapy and the biocompatibility of nanocarriers for OS treatment.

Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations.

Cold atmospheric plasma-treated liquids (PTLs) exhibit selective toxicity toward tumor cells and are provoked by a cocktail of reactive oxygen and nitrogen species in such liquids. Compared to the gaseous phase, these reactive species are more persistent in the aqueous phase. This indirect plasma treatment method has gradually gathered interest in the discipline of plasma medicine to treat cancer. PTL's motivated effect on immunosuppressive proteins and immunogenic cell death (ICD) in solid cancer cells is still not explored. In this study, we aimed to induce immunomodulation by plasma-treated Ringer's lactate (PT-RL) and phosphate-buffered saline (PT-PBS) solutions for cancer treatment. PTLs induced minimum cytotoxicity in normal lung cells and inhibited cancer cell growth. ICD is confirmed by the enhanced expression of damage-associated molecular patterns (DAMPs). We evidenced that PTLs induce intracellular nitrogen oxide species accumulation and elevate immunogenicity in cancer cells owing to the production of pro-inflammatory cytokines, DAMPs, and reduced immunosuppressive protein CD47 expression. In addition, PTLs influenced A549 cells to elevate the organelles (mitochondria and lysosomes) in macrophages. Taken together, we have developed a therapeutic approach to potentially facilitate the selection of a suitable candidate for direct clinical applications.

Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

Breast cancer is the most common type of cancer and it is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite chemotherapy's ample use, it has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target. In this paper, we review recent developments in ultrasound-guided nanocarriers for breast cancer chemotherapy, discuss the relevant challenges, and provide insights into future directions.