Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Use of curcumin and its nanopreparations in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn's disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.

Exploring the Prospective of Curcumin-loaded Nanomedicine in Brain Cancer Therapy: An Overview of Recent Updates and Patented Nanoformulations.

Cancer is a complex, one of the fatal non-communicable diseases, and its treatment has enormous challenges, with variable efficacy of traditional anti-cancer agents. By 2025, it is expected that 420 million additional cases of cancer will be diagnosed yearly. However, among various types of cancer, brain cancer treatment is most difficult due to the presence of blood-brain barriers. Nowadays, phytoconstituents are gaining popularity because of their biosafety and low toxicity to healthy cells. This article reviews various aspects related to curcumin for brain cancer therapeutics, including epidemiology, the role of nanotechnology, and various challenges for development and clinical trials. Furthermore, it elaborates on the prospects of curcumin for brain cancer therapeutics. In this article, our objective is to illuminate the anti-cancer potential of curcumin for brain cancer therapy. Moreover, it also explores how to defeat its constraints of clinical application because of poor bioavailability, stability, and rapid metabolism. This review also emphasizes the possibility of curcumin for the cure of brain cancer using cuttingedge biotechnological methods based on nanomedicine. This review further highlights the recent patents on curcumin-loaded nanoformulations for brain cancer. Overall, this article provides an overview of curcumin's potential in brain cancer therapy by considering challenges to be overwhelmed and future prospective. Moreover, this review summarizes the reported literature on the latest research related to the utility of curcumin in brain cancer therapy and aims to provide a reference for advanced investigation on brain cancer treatment.

Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects.

Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.

Oral Nanotherapeutics of Andrographolide/Carbon Monoxide Donor for Synergistically Anti-inflammatory and Pro-resolving Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology affecting the colon and rectum. Current therapeutics are focused on suppressing inflammation but are ineffective. Combining anti-inflammatory therapeutic approaches with pro-resolution might be a superior strategy for UC treatment. Andrographolide (AG), an active compound from the plant Andrographis paniculata, presented anti-inflammatory effects in various inflammatory diseases. Gaseous mediators, such as carbon monoxide (CO), have a role in inflammatory resolution. Herein, we developed a dextran-functionalized PLGA nanocarrier for efficient delivery of AG and a carbon monoxide donor (CORM-2) for synergistically anti-inflammatory/pro-resolving treatment of UC (AG/CORM-2@NP-Dex) based on PLGA with good biocompatibility, slow drug release, efficient targeting, and biodegradability. The resulting nanocarrier had a nano-scaled diameter of ∼200 nm and a spherical shape. After being coated with dextran (Dex), the resulting AG/CORM-2@NP-Dex could be efficiently internalized by Colon-26 and Raw 264.7 cells in vitro and preferentially localized to the inflamed colon with chitosan/alginate hydrogel protection by gavage. AG/CORM-2@NP-Dex performed anti-inflammatory effects by eliminating the over-production of pro-inflammatory mediator, nitric oxide (NO), and down-regulating the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), while it showed pro-resolving function by accelerating M1 to M2 macrophage conversion and up-regulating resolution-related genes (IL-10, TGF-ß, and HO-1). In the colitis model, oral administration of AG/CORM-2@NP-Dex in a chitosan/alginate hydrogel also showed synergistically anti-inflammatory/pro-resolving effects, therefore relieving UC effectively. Without appreciable systemic toxicity, this bifunctional nanocarrier represents a novel therapeutic approach for UC and is expected to achieve long-term inflammatory remission.

Copper-Single-Atom Coordinated Nanotherapeutics for Enhanced Sonothermal-Parallel Catalytic Synergistic Cancer Therapy.

Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel "BH" interfacial-confined coordination strategy to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes (HA-NC_Cu) to achieve sonothermal-catalytic synergistic therapy is reported. Notably, HA-NC_Cu demonstrates exceptional sonothermal conversion performance under low-intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high-toxicity hydroxyl radicals in response to tumor-endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA-NC_Cu originates from the CuN4 C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal-catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long-term survival rate (100%). In combination with low-intensity ultrasound irradiation, HA-NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA-MB-231 breast cancer cells, comprehensively limiting primary triple-negative breast cancer. This study highlights the applications of single-atom-coordinated nanotherapeutics in sonothermal-catalytic synergistic therapy, which may create new opportunities in biomedical research.

A Homing Missile-Like Nanotherapeutic with Single-Atom Catalytic Sites for In Situ Elimination of Intracellular Bacterial Pathogens.

Intracellular bacterial pathogens hiding in host cells tolerate the innate immune system and high-dose antibiotics, resulting in recurrent infections that are difficult to treat. Herein, a homing missile-like nanotherapeutic (FeSAs@Sa.M) composed of a single-atom iron nanozyme (FeSAs) core coated with infected macrophage membrane (Sa.M) is developed for in situ elimination of intracellular methicillin-resistant S. aureus (MRSA). Mechanically, the FeSAs@Sa.M initially binds to the extracellular MRSA via the bacterial recognition ability of the Sa.M component. Subsequently, the FeSAs@Sa.M can be transported to the intracellular MRSA-located regions in the host cell like a homing missile under the guidance of the extracellular MRSA to which it is attached, generating highly toxic reactive oxygen species (ROS) for intracellular MRSA killing via the enzymatic activities of the FeSAs core. The FeSAs@Sa.M is far superior to FeSAs in killing intracellular MRSA, proposing a feasible strategy for treating intracellular infections by in situ generating ROS in bacterial residing regions.

Multifunctional Iron Oxide Nanocarriers Synthesis for Drug Delivery, Diagnostic Imaging, and Biodistribution Study.

The aim of the current study is to design the radiolabeled and drug-loaded nanocarrier with high loading capacity and pH-dependent drug release characteristics that could effectively transport loaded compounds to various organs for efficient diagnostic imaging and chemotherapeutic drug delivery. The aqueous extract of green tea leaves was used to synthesize the small-sized iron oxide nanoparticles (IONPs). The nanoparticles were characterized with UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray analysis (EDX). Iron oxide nanoparticles with sizes smaller than 50 nm were successfully synthesized, making them suitable for in vivo studies. In drug loading trials, 94% of the drug was loaded onto the active surface of iron oxide nanoparticles from the solution. The in vitro drug release study revealed that an acidic environment (pH 4.5) effectively triggers the release of doxorubicin (DOX) from the nanoparticles as compared to a neutral environment (pH 7.4). The gamma-emitting radionuclide 99mTc was successfully labeled with IONPs for biodistribution and imaging studies. The efficiency of radiolabeling was observed to be ≥ 99%. Furthermore, the in vivo biodistribution study of radiolabeled IONPs in rabbit model showed rapid accumulation in various organs such as heart, liver, and kidneys. This work suggested that green synthesized iron oxide nanoparticles are potential nanocarriers for diagnostic imaging and efficiently distributing DOX to specific organs. The aqueous extract of green tea leaves was used for the facile green synthesis of iron oxide nanoparticles (IONPs). Furthermore, the chemotherapeutic drug doxorubicin (DOX) and gamma-emitting radionuclide 99mTc were loaded on these iron oxide nanoparticles to evaluate the in vivo biodistribution and drug delivery studies in the rabbit models.

Magnetic Micellar Nanovehicles: Prospects of Multifunctional Hybrid Systems for Precision Theranostics.

Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical micelle concentration, generating a colloidal structure with a hydrophobic core and a hydrophilic shell incorporating magnetic particles (MNPs) in one of the segments. MPMs have been investigated most prominently as contrast agents for magnetic resonance imaging (MRI), as heat generators in hyperthermia treatments, and as magnetic-susceptible nanocarriers for the delivery and release of therapeutic agents. The versatility of MPMs constitutes a powerful route to ultrasensitive, precise, and multifunctional diagnostic and therapeutic vehicles for the treatment of a wide range of pathologies. Although MPMs have been significantly explored for MRI and cancer therapy, MPMs are multipurpose functional units, widening their applicability into less expected fields of research such as bioengineering and regenerative medicine. Herein, we aim to review published reports of the last five years about MPMs concerning their structure and fabrication methods as well as their current and foreseen expectations for advanced biomedical applications.

Progress in advanced nanotherapeutics for enhanced photodynamic immunotherapy of tumor.

Clinically, the conventional treatments of cancer are still often accompanied by tumor recurrence, metastasis and other poor prognosis. Nowadays, more attention has been paid to photodynamic therapy (PDT), which is regarded as an adjuvant antineoplastic strategy with superiorities in great spatiotemporal selectivity and minimal invasiveness. In addition to eliminating tumor cells via reactive oxygen species (ROS), more meaningfully, this phototherapy can trigger immunogenic cell death (ICD) that plays a vital role in photodynamic immunotherapy (PDIT). ICD-based PDIT holds some immunotherapeutic potential due to further enhanced antitumor efficacy by utilizing various combined therapies to increase ICD levels. To help the PDIT-related drugs improve pharmacokinetic properties, bioavailability and system toxicity, multifunctional nanocarriers can be reasonably designed for enhanced PDIT. In further consideration of severe hypoxia, low immunity and immune checkpoints in tumor microenvironment (TME), advanced nanotherapeutics-mediated PDIT has been extensively studied for boosting antitumor immunity by oxygen-augment, ICD-boosting, adjuvant stimulation and combined checkpoints blockade. Herein, this review will summarize different categories of nanocarriers consisting of their material type, targeting and stimuli-responsiveness. Moreover, we will focus on the latest progress of various strategies to enhance the antitumor immune effect for PDIT and elucidate their corresponding immune-activation mechanisms. Nevertheless, there are several thorny challenges in PDIT, including limited light penetration, tumor hypoxia, immune escape and the development of novel small-molecule compounds that replace immune checkpoint inhibitors (ICIs) for easy integration into nanosystems. It is hoped that these issues raised will be helpful to the preclinical study of nanotherapeutics-based PDIT, thus accelerating the transformation of PDIT to clinical practice.

Heracleum persicum Essential Oil Nanoemulsion: A Nanocarrier System for the Delivery of Promising Anticancer and Antioxidant Bioactive Agents.

Essential oils are important compounds for the prevention and/or treatment of various diseases in which solubility and bio-accessibility can be improved by nanoemulsion systems. Heracleum persicum oil nanoemulsion (HAE-NE) was prepared and biological properties were investigated against human breast cancer cells and normal human fibroblasts foreskin. Particle size, zeta potential and poly dispersity index were 153 nm, −47.9 mV and 0.35, respectively. (E)anethole (57.9%), terpinolene (13.8%), É£-terpinene (8.1%), myrcene (6.8%), hexyl butyrate (5.2%), octyl butanoate (4.5%) and octyl acetate (3.7%) was detected in nanoemulsion. Proliferation of cancer cells at IC50 = 2.32 µg/mL was significantly (p < 0.05) inhibited, and cell migration occurred at 1.5 µL/mL. The HAE-NE at 1.5, 2.5 and 3.5 µg/concentration up-regulated caspase 3 and enhanced sub-G1 peak of cell cycle with nil cytotoxic effects in the liver, kidney and jejunum of mice. Villus height, villus width, crypt depth and goblet cells in mice group fed with 10 and 20 mg/kg body weight of HAE-NE improved. Cellular redox state in the liver indicated 10 and 20 mg/kg body weight of nanoemulsion significantly up-regulated the expression of SOD, CAT and GPx genes. Heracleum persicum oil nanoemulsion could be an eco-friendly nanotherapeutic option for pharmaceutical, cosmetological and food applications.

Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed. RESULTS: For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis. CONCLUSION: Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

Rare-Earth Doped Iron Oxide Nanostructures for Cancer Theranostics: Magnetic Hyperthermia and Magnetic Resonance Imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively investigated during the last couple of decades because of their potential applications across various disciplines ranging from spintronics to nanotheranostics. However, pure iron oxide nanoparticles cannot meet the requirement for practical applications. Doping is considered as one of the most prominent and simplest techniques to achieve optimized multifunctional properties in nanomaterials. Doped iron oxides, particularly, rare-earth (RE) doped nanostructures have shown much-improved performance for a wide range of biomedical applications, including magnetic hyperthermia and magnetic resonance imaging (MRI), compared to pure iron oxide. Extensive investigations have revealed that bigger-sized RE ions possessing high magnetic moment and strong spin-orbit coupling can serve as promising dopants to significantly regulate the properties of iron oxides for advanced biomedical applications. This review provides a detailed investigation on the role of RE ions as primary dopants for engineering the structural and magnetic properties of Fe3 O4 nanoparticles to carefully introspect and correlate their impact on cancer theranostics with a special focus on magnetic hyperthermia and MRI. In addition, prospects for achieving high-performance magnetic hyperthermia and MRI are thoroughly discussed. Finally, suggestions on future work in these two areas are also proposed.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Tunicate-Inspired Photoactivatable Proteinic Nanobombs for Tumor-Adhesive Multimodal Therapy.

Near-IR (NIR) light-responsive multimodal nanotherapeutics have been proposed to achieve improved therapeutic efficacy and high specificity in cancer therapy. However, their clinical application is still elusive due to poor biometabolization and short retention at the target site. Here, innovative photoactivatable vanadium-doped adhesive proteinic nanoparticles (NPs) capable of allowing biological photoabsorption and NIR-responsive anticancer therapeutic effects to realize trimodal photothermal-gas-chemo-therapy treatments in a highly biocompatible, site-specific manner are proposed. The photoactivatable tumor-adhesive proteinic NPs can enable efficient photothermal conversion via tunicate-inspired catechol-vanadium complexes as well as prolonged tumor retention by virtue of mussel protein-driven distinctive adhesiveness. The incorporation of a thermo-sensitive nitric oxide donor and doxorubicin into the photoactivatable adhesive proteinic NPs leads to synergistic anticancer therapeutic effects as a result of photothermal-triggered "bomb-like" multimodal actions. Thus, this protein-based phototherapeutic tumor-adhesive NPs have great potential as a spatiotemporally controllable therapeutic system to accomplish effective therapeutic implications for the complete ablation of cancer.

Smart Design of Nanomaterials for Mitochondria-Targeted Nanotherapeutics.

Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular-targeting drug-delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli-responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria-targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial-targeting nanotherapeutics.

Prospective therapeutic potential of Tanshinone IIA: An updated overview.

In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.

Designing immunogenic nanotherapeutics for photothermal-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses.

Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of "cold immune tumors" that paralyzes the immune system. The strategy of reversing "cold tumors" to "hot tumors" infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core-shell Au@Se NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMs) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment, but also offers a new insight for potential clinical application in tumor immunotherapy.

Ferroptosis-driven nanotherapeutics for cancer treatment.

The clinical efficacy of existing cancer therapies is still far from satisfactory. There is an urgent need to integrate the emerging biomedical discovery and technological innovation with traditional therapies. Ferroptosis, a non-apoptotic programmed cell death modality, has attracted remarkable attention as an emerging therapeutic target for cancer treatment, especially with the burgeoning bionanotechnology. Given the rapid progression in ferroptosis-driven cancer nanotherapeutics, we intend to outline the latest advances in this field at the intersection of ferroptosis and bionanotechnology. First, the research background of ferroptosis and nanotherapeutics is briefly introduced to illustrate the feasibility of ferroptosis-driven nanotherapeutics for cancer therapy. Second, the emerging nanotherapeutics developed to facilitate ferroptosis of tumor cells are overviewed, including promotion of the Fenton reaction, inhibition of cellular glutathione peroxidase 4 (GPX-4), and exogenous regulation of lipid peroxidation. Moreover, ferroptosis-based combination therapeutics are discussed, including the emerging nanotherapeutics combining ferroptosis with tumor imaging, phototherapy, chemotherapy and immunomodulation. Finally, the future expectations and challenges of ferroptosis-driven nanotherapeutics in clinical cancer therapy are spotlighted.

External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy.

Therapeutic, diagnostic, and imaging approaches based on nanotechnology offer distinct advantages in cancer treatment. Various nanotherapeutics have been presented as potential alternatives to traditional anticancer therapies such as chemotherapy, radiotherapy, and surgical intervention. Notably, the advantage of nanotherapeutics is mainly attributable to their accumulation and targeting ability toward cancer cells, multiple drug-carrying abilities, combined therapies, and imaging approaches. To date, numerous nanoparticle formulations have been developed for anticancer therapy and among them, metallic nanotherapeutics reportedly demonstrate promising cancer therapeutic and diagnostic efficiencies owing to their dense surface functionalization ability, uniform size distribution, and shape-dependent optical responses, easy and cost-effective synthesis procedure, and multiple anti-cancer effects. Metallic nanotherapeutics can remodel the tumor microenvironment by changing unfavorable therapeutic conditions into therapeutically accessible ones with the help of different stimuli, including light, heat, ultrasound, an alternative magnetic field, redox, and reactive oxygen species. The combination of metallic nanotherapeutics with both external and internal stimuli can be used to trigger the on-demand release of therapeutic molecules, augmenting the therapeutic efficacies of anticancer therapies such as photothermal therapy, photodynamic therapy, magnetic hyperthermia, sonodynamic therapy, chemodynamic therapy, and immunotherapy. In this review, we have summarized the role of different metallic nanotherapeutics in anti-cancer therapy, as well as their combinational effects with multiple stimuli for enhanced anticancer therapy.