ABSTRACT Breast carcinoma remains a major global health concern and continues to be one of the leading causes of cancer‐related mortality among women worldwide. Despite advancements in surgical techniques, locoregional recurrence after tumor resection poses substantial therapeutic challenges. The conventional postoperative systemic adjuvant therapies often result in significant toxicity and severe side effects. Hydrogels have emerged as promising platforms for localized therapy owing of their biodegradability, biocompatibility, structural flexibility, and multifunctional properties. Nonetheless, their broader clinical translation has been constrained by limitations such as inadequate mechanical strength, rapid degradation, and suboptimal stability. To address these challenges, nanomaterials have been integrated into hydrogel matrices to develop nanocomposite hydrogels that provide enhanced drug‐loading capacity, controlled and sustained release profiles, and improved synergistic effects for combination therapy. This article highlights the limitations of conventional breast cancer treatment modalities, explores the biomedical applications of hydrogels, and comprehensively summarizes the various nano‐hydrogel composites that have been developed for localized mono‐ and dual‐chemotherapy.
ABSTRACT MXene quantum dots (MQDs) have recently emerged as a compelling class of nanomaterials for cancer theranostics, owing to their confined electronic structure, multifunctional activation mechanisms, and favorable in vivo performance. In this review, the structure‐governed behavior of MQDs is systematically examined and interpreted, highlighting how their quantum‐scale architecture influences therapeutic functionality. The chemical and physical origins of functional diversity in MQDs are discussed, with an emphasis on dimensional miniaturization, electronic confinement, and structure–property relationships beyond biological contexts. Building on this foundation, recent advances in tumor‐selective catalytic and photothermal activation of MQDs are analyzed, highlighting Fenton‐like redox processes, near‐infrared photothermal conversion, and synergistic therapeutic modalities supported by in vivo evidence. Particular attention is given to tumor microenvironment modulation, spatiotemporal control, and imaging‐guided activation strategies that distinguish MQDs from conventional nanotherapeutics. Finally, key challenges related to clinical advancement, manufacturing scalability, safety evaluation, and regulatory considerations are evaluated. By integrating fundamental structure‐driven insights with therapeutic and clinical perspectives, MQDs are positioned as a versatile and promising platform for next‐generation precision cancer theranostics.
ABSTRACT Mitochondria (MT), commonly known as the powerhouse of the cell, performs a wide range of critical cellular functions beyond energy production. Mitochondrial dysfunction has been implicated in the pathophysiology of several diseases, making them an attractive target for therapeutic interventions. Disorders associated with mitochondrial dysfunction include metabolic disorders, cardiovascular and pulmonary diseases, neurological disorders, and cancer. Curcumin (CUR), a polyphenolic compound derived from turmeric (Curcuma longa) rhizomes, is a potent phytomolecule known for its diverse biological activities, including anticancer, anti‐inflammatory, antioxidant, antimutagenic, antidiabetic, cardioprotective, pulmonoprotective, neuroprotective, and lipid‐modifying effects. Targeting CUR to MT is a promising drug‐delivery strategy for diseases in which mitochondrial dysfunction plays a critical role in pathogenesis. This article highlights the role of mitochondrial dysfunction in the development of various diseases and discusses the significance of mitochondria‐targeted delivery of CUR using various drug‐delivery approaches. Furthermore, the article elaborates on the key challenges in mitochondrial biology and the biological barriers associated with MT‐targeted drug delivery systems. Translational challenges, clinical hurdles and limitations of MT‐targeted curcumin delivery systems are also highlighted.
ABSTRACT Thermal agents in cancer therapy have exhibited promising results in clinical investigations. Nevertheless, the rapid degradation of thermal agents limits the efficacy of thermal ablation, while thermal agents exhibiting higher thermal ablation capabilities degrade at a comparatively slower rate. Here, the current work has controlled the thermal character of PEG‐based titanium carbide (Ti 3 C 2 ) nanosheets, and developed an integrated platform for cancer therapy aimed at mitigating the limitations associated with thermal agents. The assembly of PEG onto Ti 3 C 2 , in conjunction with the substantial current flow along the Ti 3 C 2 nanosheets, improves thermal ablation through Joule heating mechanisms. The findings from degradation studies reveal that the Ti─O structural oxidation plays a significant role in facilitating the preservation of rapid degradation time. A relative cell viability of 49% was attained, alongside an input pulse length of 5 µs. The Ti 3 C 2 MXene nanosheets also facilitate the development of a sensitive and rapid sensor platform for the early detection of cancer cells. This investigation introduces an optimal thermal agent that addresses existing limitations and provides evidence of concept for Ti 3 C 2 ‐based materials in the context of highly efficient electrothermal cancer therapy.
ABSTRACT Ferroptosis, a novel form of iron‐dependent programmed cell death (PCD), has garnered extensive attention in the cancer research field in recent years. Through its unique iron‐dependent regulatory mechanisms and dynamic crosstalk with the cancer immune microenvironment (CIME), ferroptosis has established a new research paradigm for cancer therapy. This review systematically clarifies the molecular mechanisms underlying ferroptosis, thoroughly explores its dual regulatory roles within the CIME, and elaborates on the reciprocal interactions between ferroptosis and immune cell functions. It also comprehensively discusses ferroptosis‐based cancer immunotherapy strategies and their clinical translation prospects. By integrating the latest research advances, this work provides a theoretical foundation and practical guidance for the clinical application of ferroptosis in cancer immunotherapy.
ABSTRACT Ocular nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used as safer alternatives to corticosteroids for managing anterior segment inflammation and pain. By inhibiting cyclooxygenase (COX) enzymes and prostaglandin synthesis, NSAIDs effectively reduce post‐operative inflammation, allergic conjunctivitis, and intraoperative miosis during cataract surgery. Limited clinical evidence suggests benefits in preventing cystoid macular edema (CME), whereas experimental studies indicate potential therapeutic roles in retinal disorders such as diabetic retinopathy (DR), age‐related macular degeneration (AMD), and diabetic macular edema (DME) through anti‐angiogenic and neuroprotective mechanisms. Commonly used agents include diclofenac, indomethacin, ketorolac, bromfenac, flurbiprofen, and nepafenac, primarily formulated as topical ophthalmic solutions or suspensions. Compared to corticosteroids, NSAIDs do not raise intraocular pressure or induce cataracts, though mild adverse effects (such as burning, hyperemia, and keratitis) may occur; more severe complications like corneal melt are rare. This review provides a comprehensive analysis of NSAIDs in ophthalmology, covering their pharmacology, clinical applications, safety, delivery innovations, and future perspectives, including advanced formulations and emerging strategies to enhance their effectiveness in management of inflammatory ocular disorders.
Chia mucilage polysaccharides are widely used in the food and nutraceutical industries, and collagen is a well-known natural polymer in biomaterials. Although both have been extensively studied individually, their combined synergistic potential in wound management remains largely unexplored. A biomatrix comprising a combination of chia mucilage and collagen was engineered for applications in regenerating skin tissue. The resulting self-assembled chia mucilage-collagen biomatrix exhibited a densely interconnected, uniform 3D structure, providing robust structural support for the collagen component. This biomatrix displayed favorable attributes, including thermal resilience, proteolytic stability, biocompatibility, hemocompatibility, and pro-angiogenic potential, as observed in aortic explants. Additionally, it demonstrated excellent suitability as a wound-dressing material with significant wound-healing capabilities. Histological analysis revealed accelerated re-epithelization and increased collagen deposition in animals treated with the chia mucilage-collagen biomatrix compared to those treated with native collagen scaffolds. Notably, VEGFR2 expression was less pronounced in the reinforced collagen biomatrix than in native collagen, indicating the restoration of skin tissue at both anatomical and morphological levels, resembling its native state. This study underscores the promising potential of the chia mucilage-collagen biomatrix as an ideal wound dressing material and represents a pioneering step toward the development of multifunctional biomaterials based on polysaccharides and proteins.
Radioisotope therapy (RIT), a form of internal radiotherapy, eliminates tumors at close range through the emission of α particles, β particles, or Auger electrons during radionuclide decay. It has been extensively applied in the treatment of advanced localized cancers. However, the precise delivery of radionuclides to tumor sites is essential to ensure both the safety and efficacy of RIT. Additionally, intrinsic or acquired tumor resistance can significantly compromise therapeutic outcomes. In recent decades, nanocarriers have been widely investigated for radioisotope delivery, enabling the development of diverse radionuclide‐labeled nanomaterials and innovative cancer treatment strategies. This review summarizes therapeutic radioisotopes emitting α, β, or Auger particles and highlights various radionuclide‐labeled nanomedicines, including inorganic nanoparticles, organic nanoparticles, and metal–organic frameworks (MOFs). We further discuss the integration of RIT with other modalities, such as chemotherapy, immunotherapy, hyperthermia, and photodynamic therapy, using nanomedicines. Finally, we outline the future prospects and challenges associated with the development and clinical translation of radionuclide‐labeled nanomedicines.
Tuberculosis (TB) remains a global health concern, primarily due to the alarming increase in multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains of Mycobacterium tuberculosis ( Mtb ) in recent years. To effectively overcome Mtb drug resistance mechanisms, innovative therapeutic modalities such as combinatorial therapy, which integrates conventional anti‐tubercular drugs with antimicrobial peptides (AMPs), are being actively investigated. In this review, we have attempted to establish the therapeutic rationale for proposing membrane‐targeting synthetic AMPs by focusing on the unique lipid composition and structural rigidity of the Mtb cell envelope. Subsequently, we evaluated the properties and molecular mechanisms of action of five key synthetic AMPs demonstrating potent antimicrobial activity against MDR and XDR strains of Mtb , which includes LLAP (a 15‐amino‐acid LL‐37 analogue); CP26 (a 26‐amino‐acid cecropin A / mellitin hybrid); D‐LAK120 (a 27‐amino‐acid containing synthetic AMP); hLF1‐11/ hLF1‐1117‐30 (an 11‐amino‐acid human lactoferrin derivative); and MIAP (a 19‐amino‐acid magainin derivative). A detailed comparative analysis on synthetic peptides' physicochemical properties, efficacy, safety profile, pharmacodynamic characteristics and mechanisms of action are addressed. Finally, we have reported the significant translational challenges associated with the clinical application of synthetic AMPs, including systemic delivery and stability. Based on these systematic analysis, we put forth that synthetic AMPs, when utilized in combination with existing drugs, represent a highly promising therapeutic modality for overcoming drug‐resistant tuberculosis infection.
Transient bioresorbable systems operate only during the clinically indicated window and then dissolve into benign products, eliminating explantation. By matching device presence to the days to weeks period after surgery or intervention, they reduce exposure to anesthesia, reentry trauma, and risks of infection, bleeding, and wound dehiscence, while shortening recovery and lowering costs. This review surveys sensing and therapeutic platforms that use bioresorbable polymers, metals, and silicon based materials to provide structural, conductive, dielectric, and semiconducting functions. Physical sensing of pressure and temperature employs capacitive, piezoelectric, triboelectric, and resistive transduction, together with passive inductor capacitor resonant readouts. Chemical sensing of potential of hydrogen leverages fluorescence based optics, radio frequency hydrogel resonators, and ultrasound readable shape adaptive materials. Therapeutic examples include radio frequency or ultrasound powered electrical stimulation for nerve regeneration or analgesia, temporary cardiac pacing, and localized drug delivery via wireless heating reservoirs or sealed on demand valves. We present a design map linking material chemistry, thickness and geometry, and encapsulation to service lifetime, supported by accelerated soak tests and diffusion and Arrhenius models of defect driven leakage. We also offer cross modal rules and checklists for translational readiness, including standardized reporting and validation from models to living organisms.
Silk fibroin, a natural protein polymer derived from silkworms, has been widely utilized in the development of biomaterials due to its numerous advantageous properties, including versatile processability into various formats, tunable scaffold characteristics, extended biodegradation time, and low immunogenicity in the human body. This review provides a comprehensive overview of the fundamental properties of silk fibroin—such as its thermal, mechanical, optical, and electrical characteristics—offering insights that can guide the tailoring of this material for specific biomedical applications. It also summarizes relevant safety data, including ISO 10993 series evaluations, which confirm the biocompatibility of silk fibroin by demonstrating its low toxicity, blood compatibility, mild inflammatory response, absence of skin sensitization, and lack of systemic toxicity. Furthermore, this review highlights findings from in vivo models across various tissue types, including skin, bone, and nerve, underscoring the high performance of silk fibroin‐based materials in tissue repair and regeneration. Clinical trial reports are also discussed, demonstrating the therapeutic effectiveness, safety, and potential of silk fibroin‐based materials for tissue repair and reconstruction in different organs, thereby reinforcing their translational promise for real‐world medical applications.
Nanotechnology has emerged as a transformative approach to overcoming key limitations of stemcell‐based therapies, including poor cell survival, uncontrolled differentiation, low engraftment efficiency, and immune rejection. Although nanomaterial‐assisted stemcell strategies have been widely reported, a coherent framework linking material design, biological mechanisms, and clinical translation remains insufficient. This review provides a mechanism‐driven and translationally oriented synthesis of recent advances in nanotechnology‐enhanced stemcell therapy across five critical dimensions. First, we examine how nanomaterials with tunable physicochemical and mechanical properties actively regulate stemcell fate decisions. Second, we analyze nanomaterial‐based targeted delivery systems that improve localization, retention, and functional integration at injured tissues. Third, we discuss biomimetic nanomaterials that promote stemcell survival and engraftment by recreating supportive microenvironments. Fourth, we evaluate emerging immunomodulatory nanomaterials that mitigate host immune responses and enhance therapeutic tolerance. Finally, we highlight nanotechnology‐enabled imaging platforms that allow real‐time, non‐invasive monitoring of stemcell distribution and function in vivo. Distinct from prior descriptive reviews, this work integrates mechanistic insights with translational design principles, identifying key performance thresholds and clinical bottlenecks. By systematically linking nanomaterial properties to biological outcomes, this review provides a rational roadmap for developing next‐generation nanotechnology‐assisted stemcell therapies in regenerative and precision medicine.
Diabetes mellitus is a complex metabolic disorder affecting millions of people worldwide. Several studies have demonstrated significant alterations in the levels of small effector molecules such as TGFB, Wnt ligands, and sets of noncoding RNAs in diabetic conditions. These small molecules and non‐coding RNAs are released into the extracellular space through extracellular vesicles (EVs). Therefore, EVs offer an exciting opportunity to unravel new molecular and cellular mechanisms related to intercellular communication in diabetes. EVs influence pathological phenotypes in several diseases, including diabetes mellitus; however, diabetes has not been shown to alter the size of EVs. Exosomes, which are about ∼100 nanometers in diameter, are a subtype of EVs and originate in endosomes through sequential interplay with other vesicles and cell organelles. Exosomes contain diverse sets of molecules, including nucleic acids, short‐chain peptides, amino acids, lipids, cholesterols, ceramides, and metabolites. Under healthy conditions, exosomes contain constituents that are vital for the homeostasis of neighboring cells; however, under diabetic conditions, these exosomes acquire mesenchymal and fibrogenic molecules, which promote mesenchymal activation through epithelial‐to‐mesenchymal transition, endothelial‐to‐mesenchymal transition, and macrophage‐to‐mesenchymal transition in epithelial cells, endothelial cells, and M2‐type macrophages, respectively. EVs produced by stem cells may be used to treat or arrest diabetic complications. Islets from early‐stage type I diabetic patients could be safeguarded or even restored thanks to the immunomodulatory and reparative characteristics of stem cell‐derived exosomes. In this review, we describe EV constituents in non‐diabetic and diabetic conditions and their effects on mesenchymal activation and fibrogenesis in neighboring cell types, which lead to organ fibrosis. Targeting EVs offers a future therapeutic strategy to better understand diabetes mellitus and its associated fibrogenic complications in cells and tissues. The detection of exosomes in biological fluids offers a potential opportunity to establish them as diagnostic markers of diabetes mellitus.
Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by oxidative stress, tau hyperphosphorylation, amyloid‐β (Aβ) buildup, and synaptic dysfunction. Developing effective treatments for AD is hampered by the extremely selective blood–brain barrier (BBB), which prevents most therapeutic medicines from entering the central nervous system. The BBB uses carefully controlled transport mechanisms to preserve cerebral homeostasis. It is composed of endothelial cells connected by tight junctions and supported by astrocytes and pericytes. BBB rupture, on the other hand, causes increasing neuronal damage, elevated neuroinflammation, and decreased Aβ clearance in AD. Zinc‐based nanocomposites have gained attention recently as possible carriers for resolving issues related to the BBB. Enzymatic activity, antioxidant defence, and synaptic signalling are all significantly impacted by zinc, an essential trace mineral. Zinc oxide nanoparticles, Zn–EGCG complexes, and Zn‐doped polymeric systems are examples of engineered zinc nanostructures that exhibit innate neuroprotective properties, efficient drug delivery, and BBB penetration. In experimental models of AD, these multipurpose nanocarriers promote neuronal survival, inhibit Aβ aggregation, restore zinc homeostasis, and control oxidative stress. The BBB's construction and function, pathogenic changes in AD, and new approaches based on nanoparticles for targeted brain delivery are the main topics of this review. Zinc‐based nanocomposites are highlighted as dual‐purpose therapeutic and delivery systems, highlighting their potential as next‐generation therapies for Alzheimer's disease and associated neurodegenerative diseases.
ABSTRACT Pro‐apoptotic peptides have emerged as promising candidates in cancer therapeutics due to their ability to induce apoptosis in cancer cells while preferentially sparing normal tissues. By modulating intrinsic and extrinsic apoptotic pathways, these peptides offer a strategy to overcome drug resistance, a common challenge in conventional cancer treatments. Despite their potential, clinical translation is hindered by proteolytic instability, suboptimal delivery, and limited tumor specificity. Advances in peptide engineering, chemical modifications, and nanotechnology‐based delivery systems have significantly enhanced their stability, bioavailability, and targeting capabilities. Additionally, developing tumor‐penetrating peptides and stimuli‐responsive delivery platforms has further improved therapeutic precision. Combination therapies incorporating pro‐apoptotic peptides with chemotherapy, radiotherapy, or immunotherapy have demonstrated synergistic effects, enhancing efficacy and minimizing side effects. Preclinical studies and clinical trials involving compounds like plitidepsin, PEP‐010, GO‐203‐2C, and CIGB‐300 underscore the promise of these therapies, though further research is necessary to address current limitations. Overcoming delivery challenges, refining tumor‐specific targeting, and expanding combination strategies will be essential for maximizing their therapeutic potential. This review highlights current advancements in pro‐apoptotic peptide‐based cancer therapies, including mechanisms of action, design strategies, and delivery systems. Moreover, we discuss challenges in clinical translation and explore future directions for optimizing their therapeutic potential.
ABSTRACT Ovarian cancer (OC) is a formidable adversary, often diagnosed at advanced stages with limited treatment options. This review article delves into the innovative and promising field of nucleic acid‐based vaccines, which have ushered in a new era in cancer immunotherapy, particularly in the context of OC. These vaccines, utilizing both DNA and RNA platforms, offer a unique approach to harness the power of the immune system in targeting OC cells. Our exploration begins with a comprehensive overview of OC, emphasizing its heterogeneous nature and the pressing need for more effective therapies. We then elucidate the fundamental principles of immunotherapy and the role of the immune system in combating OC, setting the stage for the introduction of nucleic acid‐based vaccines. The review delves into the mechanisms and design principles behind nucleic acid vaccines, highlighting their potential to trigger robust and specific immune responses. A critical examination of preclinical studies and clinical trials showcases the promising results achieved with these vaccines, offering hope to OC patients. Challenges, such as delivery and combination therapies, are discussed, alongside insights into the patient experience and quality of life improvements. Regulatory approvals and market dynamics are analyzed, revealing the evolving landscape of OC immunotherapy. We conclude with a discussion of the transformative impact of nucleic acid‐based vaccines in this field and the potential for a brighter future in the battle against OC. Thus, the potential of nucleic acid‐based vaccines offers optimism in the continuous effort to improve OC patients’ prognosis and quality of life.
ABSTRACT Chemotherapy remains a cornerstone of cancer treatment, and chemotherapeutic agents are administered in various forms to a wide range of patients. However, its efficacy is typically limited by nonspecific toxicity. Active targeted nanoparticles (NPs) have emerged as a promising strategy for chemotherapeutic drug delivery. However, after nanocarriers enter the bloodstream, they face multiple barriers such as blood circulation, the tumor microenvironment, cellular uptake, and multidrug resistance (MDR). These barriers prevent nanocarriers from achieving their expected efficacy, ultimately hindering their clinical translation. This review begins with an introduction to the active targeting strategies for NP‐based carriers. It then presents the main biological barriers encountered by nanocarriers, from the blood to cells, and systematically explores the multifaceted contributions of active targeted NPs to improving therapeutic outcomes on the systemic, cellular, and molecular levels by prolonging blood circulation, enabling controlled drug release, and reversing MDR. Furthermore, this review highlights the recent advances in NP‐mediated combination therapies, including magnetic hyperthermia, photothermal therapy, photodynamic therapy, and sonodynamic therapy, emphasizing their potential for enhancing chemotherapeutic efficacy. Finally, the progress and current limitations of nanocarriers in clinical applications are discussed. This review provides innovative perspectives for the development of advanced NP‐based chemotherapeutic nanocarriers.
ABSTRACT Although conventional vaccines and recent mRNA‐lipid nanoparticle platforms have revolutionized disease prevention, challenges remain regarding thermal stability, targeted delivery, and adverse immunogenic reactions. Exosomes, naturally occurring nanoscale extracellular vesicles (30–200 nm), have recently emerged as a highly innovative, biocompatible, and personalized platform for vaccine delivery. This comprehensive review systematically explores the latest advancements and structural innovations in exosome‐based vaccines. To highlight the innovation of these biological vectors, we categorize and critically evaluate exosomes based on their distinct cellular origins: Dendritic Cell‐derived exosomes (DEXs) possessing robust antigen‐presenting capabilities; Tumor‐derived exosomes (TDEs) harboring a rich repertoire of endogenous tumor antigens for cancer immunotherapy; and Plant‐derived exosome‐like nanovesicles (PELNVs) serving as an economical, highly scalable, and safe alternative vector. Furthermore, we provide a comparative analysis between exosome‐based platforms and traditional vaccines, emphasizing their superior capacity to cross biological barriers, facilitate direct or cross‐presentation of antigens, and elicit potent cellular and humoral immune responses. The therapeutic and prophylactic efficacies of these vaccines against various malignancies and severe infectious diseases (both viral, such as HIV, based on the “Trojan exosome” hypothesis, and non‐viral) are thoroughly discussed. Finally, we summarize ongoing clinical trials, critically assess potential biosafety risks (such as off‐target effects and oncogenic cargo transfer), and outline optimization strategies for large‐scale manufacturing. Ultimately, exosome‐based vaccines represent a paradigm shift in immunization, paving the way for next‐generation personalized medicine.
Polymer-drug conjugates have seen limited exploration in antimalarial therapy, despite their successful development for cancer and other diseases. With rising resistance and a critical shortage of first-line treatments for severe malaria, innovative drug delivery strategies are urgently needed to maximize the currently available drugs. Building on our previous work that demonstrated a water-soluble polymer-lumefantrine conjugate for the intravenous treatment of severe malaria, we investigated the influence of linker chemistry on drug release rate and kinetics of a new polyethylene glycol-lumefantrine conjugate under conditions relevant to malaria pathophysiology. Four homologous aliphatic diacid linkers (succinic, glutaric, adipic, and dodecanedioic acids) containing 4, 5, 6, and 12 carbon atoms, respectively, were introduced between the polymer and the drug. The conjugates were structurally well-defined and selectively cleaved at the ester bond under acidic conditions (pH 5.5), releasing only free lumefantrine, while remaining stable in human plasma (pH 7.4). Drug release rates were inversely proportional to linker length, with only the succinic acid-linked conjugate, which exhibited an initial burst release, deviating from first-order kinetic models. Complete inhibition of the Plasmodium falciparum NF54 strain was observed in vitro with a divalent variant of the succinic acid-linked conjugate, underscoring its potential for effective therapeutic action.
