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Due to the reduced absorption, light scattering, and tissue autofluorescence in the NIR-II (1000-1700 nm) region, significant efforts are underway to explore diverse material platforms for in vivo fluorescence imaging, particularly for cancer diagnostics and image-guided interventions. Of the reported imaging agents, nanoparticles derived from conjugated polymers (CPNs) offer unique advantages to alternative materials including biocompatibility, remarkable absorption cross-sections, exceptional photostability, and tunable emission behavior independent of cell labeling functionalities. Herein, the current state of NIR-II emitting CPNs are summarized and structure-function-property relationships are highlighted that can be used to elevate the performance of next-generation CPNs. Methods for particle processing and incorporating cancer targeting modalities are discussed, as well as detailed characterization methods to improve interlaboratory comparisons of novel materials. Contemporary methods to specifically apply CPNs for cancer diagnostics and therapies are then highlighted. This review not only summarizes the current state of the field, but offers future directions and provides clarity to the advantages of CPNs over other classes of imaging agents., (© 2024 Wiley‐VCH GmbH.)

Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations., (© 2024 Wiley‐VCH GmbH.)

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high-intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies., (© 2024 Wiley‐VCH GmbH.)

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy., (© 2024 Wiley‐VCH GmbH.)

Despite significant breakthroughs in immunotherapy, the limitations of inadequate immune stimulation and stubborn immune resistance continue to present opportunities and challenges. Therefore, a two-pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3-dioxygenase (IDO)-mediated pathway, is devised to elicit systemic anti-tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)-specific driven nanoagent is composed of a tetrasulfide bond-bridged mesoporous silica layer (MON) coated up-conversion nanoparticles as a nano-carrier, combines Fe 2+ , curcumin, and indoximod for operating chemodynamic therapy/chemotherapy/immunotherapy. The consumption of glutathione (GSH) caused by MON degradation, the Fenton reaction of Fe 2+ , and curcumin triggering mitochondrial damage collectively exacerbate the oxidative stress, leading to a violent immunoreaction and reversal of the immunosuppressive TME through a combination of IDO-inhibitors. Meanwhile, upconversion luminescence (UCL) imaging serves as a significant guiding tool for drug delivery and the treatment of nanoagents. In vivo and in vitro experiment results demonstrate that the nanosystem not only effectively inhibits the growth of primary tumors but also induces immune priming and memory effects to reject re-challenged tumors. The strategy as a complementary approach displays great potential for future immunotherapy along with other multimodal treatment modes., (© 2023 Wiley‐VCH GmbH.)

Immunotherapy based on nanoplatforms is a promising approach to treat cancer and infectious diseases, and it has achieved considerable progress in clinical practices. Cell membrane-based nanoplatforms endow nanoparticles with versatile characteristics, such as half-life extension, targeting ability, and immune-system regulation. However, monotypic cell membrane usually fails to provoke strong immune response for immunotherapy while maintaining good biosafety. The integration of different cell-membrane types provides a promising approach to construct multifunctional nanoplatforms for improved immunotherapeutic efficacy by enhancing immunogenicity or targeting function, evading immune clearance, or combining with other therapeutic modalities. In this review, the design principles, preparation strategies, and applications of hybrid cell membrane-based nanoplatforms for cancer and infection immunotherapy are first discussed. Furthermore, the challenges and prospects for the potential clinical translation of hybrid cell membrane-based nanoplatforms are discussed., (© 2024 Wiley‐VCH GmbH.)

Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, this work integrates hafnium oxide (HfO 2 ) nanoparticles (radiosensitizer) and 7-Ethyl-10-hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)-coated core-shell nanoplatform (HfO 2 @PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co-delivery of HfO 2 /SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8 + T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor-bearing mice is efficiently inhibited. Moreover, the HfO 2 @PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation., (© 2024 Wiley‐VCH GmbH.)

Alzheimer's disease (AD) is a neurodegenerative condition that exhibits a gradual decline in cognitive function and is prevalent among a significant number of individuals globally. The use of small interfering RNA (siRNA) molecules in RNA interference (RNAi) presents a promising therapeutic strategy for AD. Lipid nanoparticles (LNPs) have been developed as a delivery vehicle for siRNA, which can selectively suppress target genes, by enhancing cellular uptake and safeguarding siRNA from degradation. Numerous research studies have exhibited the effectiveness of LNP-mediated siRNA delivery in reducing amyloid beta (Aβ) levels and enhancing cognitive function in animal models of AD. The feasibility of employing LNP-mediated siRNA delivery as a therapeutic approach for AD is emphasized by the encouraging outcomes reported in clinical studies for other medical conditions. The use of LNP-mediated siRNA delivery has emerged as a promising strategy to slow down or even reverse the progression of AD by targeting the synthesis of tau phosphorylation and other genes linked to the condition. Improvement of the delivery mechanism and determination of the most suitable siRNA targets are crucial for the efficacious management of AD. This review focuses on the delivery of siRNA through LNPs as a promising therapeutic strategy for AD, based on the available literature., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Lipid-based nanoparticles (LBNPs) are currently the most promising vehicles for nucleic acid drug (NAD) delivery. Although their clinical applications have achieved success, the NAD delivery efficiency and safety are still unsatisfactory, which are, to a large extent, due to the existence of multi-level physiological barriers in vivo. It is important to elucidate the interactions between these barriers and LBNPs, which will guide more rational design of efficient NAD vehicles with low adverse effects and facilitate broader applications of nucleic acid therapeutics. This review describes the obstacles and challenges of biological barriers to NAD delivery at systemic, organ, sub-organ, cellular, and subcellular levels. The strategies to overcome these barriers are comprehensively reviewed, mainly including physically/chemically engineering LBNPs and directly modifying physiological barriers by auxiliary treatments. Then the potentials and challenges for successful translation of these preclinical studies into the clinic are discussed. In the end, a forward look at the strategies on manipulating protein corona (PC) is addressed, which may pull off the trick of overcoming those physiological barriers and significantly improve the efficacy and safety of LBNP-based NADs delivery., (© 2023 Wiley‐VCH GmbH.)

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS 2 , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS 2 possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS 2 promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC., (© 2023 Wiley‐VCH GmbH.)

Photodynamic therapy (PDT) has recently been considered a potential tumor therapy due to its time-space specificity and non-invasive advantages. PDT can not only directly kill tumor cells by using cytotoxic reactive oxygen species but also induce an anti-tumor immune response by causing immunogenic cell death of tumor cells. Although it exhibits a promising prospect in treating tumors, there are still many problems to be solved in its practical application. Tumor hypoxia and immunosuppressive microenvironment seriously affect the efficacy of PDT. The hypoxic and immunosuppressive microenvironment is mainly due to the abnormal vascular matrix around the tumor, its abnormal metabolism, and the influence of various immunosuppressive-related cells and their expressed molecules. Thus, reprogramming the tumor microenvironment (TME) is of great significance for rejuvenating PDT. This article reviews the latest strategies for rejuvenating PDT, from regulating tumor vascular matrix, interfering with tumor cell metabolism, and reprogramming immunosuppressive related cells and factors to reverse tumor hypoxia and immunosuppressive microenvironment. These strategies provide valuable information for a better understanding of the significance of TME in PDT and also guide the development of the next-generation multifunctional nanoplatforms for PDT., (© 2023 Wiley‐VCH GmbH.)

Messenger RNA (mRNA)-based therapy has emerged as a powerful, safe, and rapidly scalable therapeutic approach that involves technologies for both mRNA itself and the delivery vehicle. Although there are some unique challenges for different applications of mRNA therapy, a common challenge for all mRNA therapeutics is the transport of mRNA into the target cell cytoplasm for sufficient protein expression. This review is focused on the behaviors at the cellular level of nanotechnology-mediated mRNA delivery systems, which have not been comprehensively reviewed yet. First, the four main therapeutic applications of mRNA are introduced, including immunotherapy, protein replacement therapy, genome editing, and cellular reprogramming. Second, common types of mRNA cargos and mRNA delivery systems are summarized. Third, strategies to enhance mRNA delivery efficiency during the cellular trafficking process are highlighted, including accumulation to the cell, internalization into the cell, endosomal escape, release of mRNA from the nanocarrier, and translation of mRNA into protein. Finally, the challenges and opportunities for the development of nanotechnology-mediated mRNA delivery systems are presented. This review can provide new insights into the future fabrication of mRNA nanocarriers with desirable cellular trafficking performance., (© 2023 Wiley‐VCH GmbH.)

Cancer development and progression of cancer are closely associated with the activation of oncogenes and loss of tumor suppressor genes. Nucleic acid drugs (e.g., siRNA, mRNA, and DNA) are widely used for cancer therapy due to their specific ability to regulate the expression of any cancer-associated genes. However, nucleic acid drugs are negatively charged biomacromolecules that are susceptible to serum nucleases and cannot cross cell membrane. Therefore, specific delivery tools are required to facilitate the intracellular delivery of nucleic acid drugs. In the past few decades, a variety of nanoparticles (NPs) are designed and developed for nucleic acid delivery and cancer therapy. In particular, the polymeric NPs in response to the abnormal redox status in cancer cells have garnered much more attention as their potential in redox-triggered nanostructure dissociation and rapid intracellular release of nucleic acid drugs. In this review, the important genes or signaling pathways regulating the abnormal redox status in cancer cells are briefly introduced and the recent development of redox-responsive NPs for nucleic acid delivery and cancer therapy is systemically summarized. The future development of NPs-mediated nucleic acid delivery and their challenges in clinical translation are also discussed., (© 2023 Wiley-VCH GmbH.)

Zeolite imidazole framework-8 (ZIF-8) is the most prestigious one among zeolitic imidazolate framework (ZIF) with tunable dimensions and unique morphological features. Utilizing its synthetic adjustability and structural regularity, ZIF-8 exhibits enhanced flexibility, allowing for a wide range of functionalities, such as loading of nanoparticle components while preserving biomolecules activity. Extensive efforts are made from investigating synthesis techniques to develop novel applications over decades. In this review, the development and recent progress of various synthesis approaches are briefly summarized. In addition, its interesting properties such as adjustable porosity, excellent thermal, and chemical stabilities are introduced. Further, five representative biomedical applications are highlighted based on above physicochemical properties. Finally, the remaining challenges and offered insights into the future outlook are also discussed. This review aims to understand the co-relationships between structures and biomedical functionalities, offering the opportunity to construct attractive materials with promising characteristics., (© 2023 Wiley-VCH GmbH.)

Thermal ablation is a crucial therapeutic modality for hepatocellular carcinoma (HCC), but its efficacy is often hindered by the high recurrence rate attributed to insufficient ablation. Furthermore, the residual tumors following insufficient ablation exhibit a more pronounced immunosuppressive state, which accelerates the disease progression and leads to immune checkpoint blockade (ICB) resistance. Herein, evidence is presented that heightened intratumoral lactate accumulation, stemming from the augmented glycolytic activity of postablative residual HCC cells, may serve as a crucial driving force in exacerbating the immunosuppressive state of the tumor microenvironment (TME). To address this, an injectable nanoparticles-hydrogel composite system (LOX-MnO 2 @Gel) is designed that gradually releases lactate oxidase (LOX)-loaded hollow mesoporous MnO 2 nanoparticles at the tumor site to continuously deplete intratumoral lactate via a cascade catalytic reaction. Using subcutaneous and orthotopic HCC tumor-bearing mouse models, it is confirmed that LOX-MnO 2 @Gel-mediated local lactate depletion can transform the immunosuppressive postablative TME into an immunocompetent one and synergizes with ICB therapy to significantly inhibit residual HCC growth and lung metastasis, thereby prolonging the survival of mice postablation. The work proposes an appealing strategy for synergistically combining antitumor metabolic therapy with immunotherapy to combat postablative HCC recurrence., (© 2023 Wiley-VCH GmbH.)

A portable sweat urea sensing system is a promising solution to satisfy the booming requirement of kidney function tele-monitoring. However, the complicated manufacturing route and the cumbersome electrochemical testing system still need to be improved to develop the urea point-of-care testing (POCT) and tele-monitoring devices. Here, a universal technical route based on a high-throughput automatic laser printing strategy for fabricating the portable integrated urea monitoring system is proposed. This integrated system includes a high-performance laser-printed urea sensing electrode, a planar three-electrode system, and a self-developed wireless mini-electrochemical workstation. A precursor donor layer is activated by laser scribing and in situ transferred into functional nanoparticles for the drop-on-demand printing of the urea sensing electrode. The obtained electrodes show high sensitivity, low detection limit, fast response time, high selectivity, good average recovery, and long-term stability for urea sensing. Additionally, a laser-induced graphene circuit-based miniature planar three-electrode system and a wireless mini-electrochemical workstation are designed for sensing data collection and transmitting, achieving real-time urea POCT and tele-monitoring. This scalable method provides a universal solution for high-throughput and ultra-fast fabrication of urea-sensing electrodes. The portable integrated urea monitoring system is a competitive option to achieve cost-effective POCT and tele-monitoring for kidney function., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)

Surgery is a traditional tumor treatment, and immunotherapy can reduce the postoperative recurrence of tumors. However, the intrinsic limits of low responsive rate and non-tumor specificity of immunotherapy agents are still insufficient to address therapeutic demands. Herein, the macrophages membrane camouflaged nanoparticles (NPs), named M@PFC, consisting of the aggregation-induced emission photosensitizer (PF3-PPh 3 ) and immune adjuvant (CpG), are reported. As the protein on the membrane interacts with the vascular cell adhesion molecule 1 (VCAM-1) of cancer cells, M@PFC efficiently transports CpG to the tumor. Meanwhile, M@PFC can evade clearance by the immune system and prolong the circulation time in vivo; thus, enhancing their accumulation in tumors. PF3-PPh 3 promotes high production of reactive oxygen species (ROS) and triggers immune cell death (ICD) in tumor cells under light exposure. Importantly, CpG enrichment in tumors can stimulate tumor cells to produce immune factors to assist in enhancing ICD effects. The synergistic effect combining the PDT properties of the aggregation-induced emission (AIE)-active photosensitizer and immunotherapy properties of CpG significantly delays tumor recurrence after surgery. In conclusion, this strategy achieves the synergistic activation of the immune system for anti-tumor activity, providing a novel paradigm for the development of therapeutic nanodrugs to delay postoperative tumor recurrence., (© 2023 Wiley-VCH GmbH.)

The nanodelivery system provides a novel direction for disease diagnosis and treatment; however, its delivery effectiveness is restricted by the short biological half-life and inadequate tumor targeting. The immune evasion properties and homologous targeting capabilities of natural cell membranes, particularly those of cancer cell membranes (CCM), have gained significant interest. The integration of CCM and nanoparticles has resulted in the emergence of CCM-based nanoplatforms (CCM-NPs), which have gained significant attention due to their unique properties. CCM-NPs not only prolong the blood circulation time of core nanoparticles, but also direct them for homologous tumor targeting. Herein, the history and development of CCM-NPs as well as how these platforms have been used for biomedical applications are discussed. The application of CCM-NPs for cancer therapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CCM-NPs., (© 2023 Wiley-VCH GmbH.)

In recent years, messenger RNA (mRNA) vaccines have exhibited great potential to replace conventional vaccines owing to their low risk of insertional mutagenesis, safety and efficacy, rapid and scalable production, and low-cost manufacturing. With the great achievements of chemical modification and sequence optimization methods of mRNA, the key to the success of mRNA vaccines is strictly dependent on safe and efficient gene vectors. Among various delivery platforms, non-viral mRNA vectors could represent perfect choices for future clinical translation regarding their safety, sufficient packaging capability, low immunogenicity, and versatility. In this review, the recent progress in the development of non-viral mRNA vectors is focused on. Various organic vectors including lipid nanoparticles (LNPs), polymers, peptides, and exosomes for efficient mRNA delivery are presented and summarized. Furthermore, the latest advances in clinical trials of mRNA vaccines are described. Finally, the current challenges and future possibilities for the clinical translation of these promising mRNA vectors are also discussed., (© 2023 Wiley-VCH GmbH.)

Tumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double-sensitive composite hydrogel embedded with tetrasulfide-bridged mesoporous silica (4S-MSNs) is developed. The incorporation of 4S-MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S-MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S-MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence., (© 2023 Wiley-VCH GmbH.)

Atherosclerosis is a systemic pathophysiological condition contributing to the development of majority of polyvascular diseases. Nanomedicine is a novel and rapidly developing science. Due to their small size, nanoparticles are freely transported in vasculature, and have been widely employed as tools in analytical imaging techniques. Furthermore, the application of nanoparticles also allows target intervention, such as drug delivery and tissue engineering regenerative methods, in the management of major vascular diseases. Therefore, by summarizing the physical and chemical characteristics of common nanoparticles used in diagnosis and treatment of vascular diseases, we discuss the details of these applications from cellular, molecular, and in vivo perspectives in this review. Furthermore, we also summarize the status and challenges of the application of nanoparticles in clinical translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2023 Wiley Periodicals LLC.)

Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu 2-x S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu 2-x S, the performance of Cu 2-x S based phototherapy still cannot meet the requirement of the clinical application to now. To overcome this limitation, engineering of Cu 2-x S to improve the phototherapy performance by increasing light absorption has attracted extensive attention. For better guidance of Cu 2-x S engineering, we outline the currently engineering method being explored, including (1) structural engineering, (2) compositional engineering, (3) functional engineering, and (4) performance engineering. Also, the relationship between the engineering method and phototherapy performance was discussed in this review. In addition, the further development of Cu 2-x S based phototherapy is prospected, including smart materials based phototherapy, phototherapy induced immune microenvironment modulation et al. This review will provide new ideas and opportunities for engineering of Cu 2-x S with better phototherapy performance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2023 Wiley Periodicals LLC.)

Multimodal cancer therapies show great promise in synergistically enhancing anticancer efficacy through different mechanisms. However, most current multimodal therapies either rely on complex assemblies of multiple functional nanomaterials and drug molecules or involve the use of nanomedicines with poor in vivo degradability/metabolizability, thus restricting their clinical translatability. Herein, a nanoflower-medicine using iron ions, thioguanine (TG), and tetracarboxylic porphyrin (TCPP) are synthesized as building blocks through a one-step hydrothermal method for combined chemo/chemodynamic/photodynamic cancer therapy. The resulting nanoflowers, consisting of low-density Fe 2 O 3 core and iron complex (Fe-TG and Fe-TCPP compounds) shell, exhibit high accumulation at the tumor site, desirable degradability in the tumor microenvironment (TME), robust suppression of tumor growth and metastasis, as well as effective reinvigoration of host antitumor immunity. Triggered by the low pH in tumor microenvironment, the nanoflowers gradually degrade after internalization, contributing to the effective drug release and initiation of high-efficiency catalytic reactions precisely in tumor sites. Moreover, iron ions can be eliminated from the body through renal clearance after fulfilling their mission. Strikingly, it is also found that the multimodal synergistic therapy effectively elicits the host antitumor immunity without inducing additional toxicity. This easy-manufactured and degradable multimodal therapeutic nanomedicine is promising for clinical precision oncology., (© 2023 Wiley-VCH GmbH.)

The pioneering work on liposomes in the 1960s and subsequent research in controlled drug release systems significantly advances the development of nanocarriers (NCs) for drug delivery. This field is evolved to include a diverse array of nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and more, each tailored to specific therapeutic applications. Despite significant achievements, the clinical translation of nanocarriers is limited, primarily due to the low efficiency of drug delivery and an incomplete understanding of nanocarrier interactions with biological systems. Addressing these challenges requires interdisciplinary collaboration and a deep understanding of the nano-bio interface. To enhance nanocarrier design, scientists employ both physics-based and data-driven models. Physics-based models provide detailed insights into chemical reactions and interactions at atomic and molecular scales, while data-driven models leverage machine learning to analyze large datasets and uncover hidden mechanisms. The integration of these models presents challenges such as harmonizing different modeling approaches and ensuring model validation and generalization across biological systems. However, this integration is crucial for developing effective and targeted nanocarrier systems. By integrating these approaches with enhanced data infrastructure, explainable AI, computational advances, and machine learning potentials, researchers can develop innovative nanomedicine solutions, ultimately improving therapeutic outcomes., (© 2024 Wiley‐VCH GmbH.)

Pathogen-mimicking nanoparticles have emerged at the forefront of vaccine delivery technology, offering potent immune activation and excellent biocompatibility. Among these innovative carriers, mannan, a critical component of yeast cell walls, shows promise as an exemplary vaccine carrier. Nevertheless, it faces challenges like unpredictable immunogenicity, rapid elimination, and limited antigen loading due to high water solubility. Herein, mannan with varying carbon chain ratios is innovatively modified, yielding a series of dodecyl chains modified mannan (Mann-C 12 ). Through meticulous screening, a mannan variant with a 40% grafting ratio is pinpointed as the optimal vaccine carrier. Further RNA sequencing confirms that Mann-C 12 exhibits desired immunostimulatory characteristics. Coupled with antigen peptides, Mann-C 12 /OVA 257-280 nanovaccine initiates the maturation of antigen-presenting cells by activating the TLR4 and Dectin-2 pathways, significantly boosting antigen utilization and sparking antigen-specific immune responses. In vivo, experiments utilizing the B16-OVA tumor model underscore the exceptional preventive capabilities of Mann-C 12 /OVA 257-280 . Notably, when combined with immune checkpoint blockade therapy, it displays a profound synergistic effect, leading to marked inhibition of tumor growth. Thus, the work has yielded a pathogen-like nanovaccine that is both simple to prepare and highly effective, underscoring the vast potential of mannan-modified nanovaccines in the realm of cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO 2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO 2 and MnO. Under acidic TME, CaO 2 reacts with acid to release Ca 2+ to induce mitochondrial damage and simultaneously produces O 2 and H 2 O 2 , when the loaded MnO exerts Fenton-like activity to produce ·OH and O 2 based on the produced H 2 O 2 . The generated O 2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca 2 +  overloading, GSH depletion induced by Mn 2+ , and Mn 2+  mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Plastic waste comprises polymers of different chemicals that disintegrate into nanoplastic particles (NPLs) of 1-100-nm size, thereby littering the environment and posing a threat to wildlife and human health. Research on NPL contamination has up to now focused on the ecotoxicology effects of the pollution rather than the health risks. This review aimed to speculate about the possible properties of carcinogenic and neurotoxic NPL as pollutants. Given their low-dimensional size and high surface size ratio, NPLs can easily penetrate biological membranes to cause functional and structural damage in cells. Once inside the cell, NPLs can interrupt the autophagy flux of cellular debris, alter proteostasis, provoke mitochondrial dysfunctions, and induce endoplasmic reticulum stress. Harmful metabolic and biological processes induced by NPLs include oxidative stress (OS), ROS generation, and pro-inflammatory reactions. Depending on the cell cycle status, NPLs may direct DNA damage, tumorigenesis, and lately carcinogenesis in tissues with high self-renewal capabilities like epithelia. In cells able to live the longest like neurons, NPLs could trigger neurodegeneration by promoting toxic proteinaceous aggregates, OS, and chronic inflammation. NPL genotoxicity and neurotoxicity are discussed based on the gathered evidence, when available, within the context of the intracellular uptake of these newcomer nanoparticles. In summary, this review explains how the risk evaluation of NPL pollution for human health may benefit from accurately monitoring NPL toxicokinetics and toxicodynamics at the intracellular resolution level., (© 2024 John Wiley & Sons Ltd.)

Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down-regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2-deoxy-D-glucose (2DG) is an anti-glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low-temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx-BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as-prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR-I/II fluorescence imaging-guided starvation/MPTT/PDT synergy therapy for tumors., (© 2024 Wiley‐VCH GmbH.)

Dielectrophoresis (DEP) is a fast and reliable nanoparticle recovery method that utilizes nonuniform electric fields to manipulate particles based on their material composition and size, enabling recovery of biologically-derived nanoparticles from plasma for diagnostic applications. When applying DEP to undiluted human plasma, collection of endogenous albumin proteins was observed at electric field gradients much lower than predicted by theory to collect molecular proteins. To understand this collection, nanoparticle tracking analysis of bovine serum albumin (BSA) dissolved in 0.5× phosphate-buffered saline was performed and showed that albumin spontaneously formed aggregate nanoparticles with a mean diameter of 237 nm. These aggregates experienced a dielectrophoretic force as a function of aggregate radius rather than the diameter of individual protein molecules which contributed to their collection. In high conductance buffer (6.8 mS/cm), DEP was able to move these aggregates into regions of high electric field gradient, and in lower conductance buffer (0.68 mS/cm), these aggregates could be moved into high or low gradient regions depending on the applied frequency. Disruption of BSA aggregates using a nonionic detergent significantly decreased the particle diameter, resulting in decreased dielectrophoretic collection of albumin which increased the collection consistency of particles of interest. These results provide techniques to manipulate albumin aggregates via DEP, which impacts collection of diagnostic biomarkers., (© 2024 The Author(s). ELECTROPHORESIS published by Wiley‐VCH GmbH.)

Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it in vitro and in vivo. An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The P app of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC 0-∞ (μg/L*h): 5.356 ± 1.144 vs 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Osteosarcoma (OS) is a "cold" tumor enriched in noninflammatory M2 phenotype tumor-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumor microenvironment (TME), generated by factors such as excess hydrogen (H + ) ions and high lactate levels, activates immunosuppressive cells, further promoting a suppressive tumor immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO 3 )/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) is developed. CaCO 3 nanoparticles are used to neutralize H + ions and alleviate the suppressive TIME, and the loaded SHK not only synergizes with photodynamic therapy (PDT) but also inhibits lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumor suppression and comprehensive beneficial effects on antitumor immune responses. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, shows a remarkable ability to eliminate distant tumors and promote long-term immune memory function to protect against rechallenged tumors. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME., (© 2024 Wiley‐VCH GmbH.)

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy., (© 2024 Wiley‐VCH GmbH.)

Optical bioimaging is an ever-growing field that benefits both from the fast progress of optical instrumentation and modalities, and from the development of light-emitting probes. The efficacy of molecular fluorescent dyes is crucial, yet hindered by limited brightness and hydrophilicity. Addressing these challenges, self-stabilized fluorogenic organic nanoparticles only made of pure dyes (dFONs) are introduced in this work. Comprising thiol-sensitive fluorogenic chromophores, these dFONs exhibit enhanced brightness exclusively in the presence of biological thiols, notably glutathione, overcoming the need for water-solubilizing moieties. Importantly, these nanoparticles demonstrate large fluorescence and one- and two-photon brightness, enabling sensitive bioimaging of intracellular thiols at micromolar concentrations. Notably, only the pristine fluorogenic nanoparticles can penetrate the cells and does not require to wash the cells before imaging, emphasizing their unique role as dye carriers, fluorogenic probes and ease of use. This work highlights the transformative potential of dFONs in advancing optical bioimaging, paving the way for the use of dFONs not just as tracers, but also now as biosensors and ultimately in the future as biomarkers., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Activatable near-infrared (NIR) fluorogenic probes offer a potent tool for real-time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluorescence imaging and in ILD diagnosis. In this study, an effective utilization of ionizable lipid nanoparticles (iLNPs) is presented as liver-targeted carriers for efficient delivery of fluorogenic probes, aiming to overcome biodistribution barriers and achieve accurate detection of hepatic biomarkers. Based on this strategy, a liver-targeted NIR fluorogenic nanoprobe hCy-H 2 O 2 @iLNP is prepared using hCy-H 2 O 2 as a small molecule reporter for visualizing the over-produced hydrogen peroxide (H 2 O 2 ) in situ of liver. Notably, iLNPs not only significantly enhance probe accumulation in the liver, but also enable sequence activation of fluorescent nanoprobes. This response is achieved through primary liposome-dissociation release and secondary hCy-H 2 O 2 response with pathological H 2 O 2 , enabling high-precision detection of oxidative stress in hepatocytes. These distinctive features facilitate accurate early diagnosis of acetaminophen (APAP)-induced inflammatory liver injury as well as lipopolysaccharide (LPS)-induced hepatitis. Therefore, the organ-targeted nanoprobe design strategy showcasts great potential for early and accurate diagnosis of lesions in situ in different organs., (© 2024 Wiley‐VCH GmbH.)

Organic phototheranostics simultaneously having fluorescence in the second near-infrared (NIR-II, 1000-1700 nm) window, and photothermal and photodynamic functions possess great prospects in tumor diagnosis and therapy. However, such phototheranostics generally suffer from low brightness and poor photodynamic performance due to severe solvatochromism. Herein, an organic NIR-II fluorophore AS1, which possesses an inverted dependence of fluorescence quantum yield on polarity, is reported to serve as potent phototheranostics for tumor diagnosis and therapy. After encapsulation of AS1 into nanostructures, the obtained phototheranostics (AS1 R ) exhibit high extinction coefficients (e.g., 68200 L mol -1  cm -1 at 808 nm), NIR-II emission with high fluorescence quantum yield up to 4.7% beyond 1000 nm, photothermal conversion efficiency of ≈65%, and 1 O 2 quantum yield up to 4.1%. The characterization of photophysical properties demonstrates that AS1 R is superior to other types of organic phototheranostics in brightness, photothermal effect, and photodynamic performance at the same mass concentration. The excellent phototheranostic performance of AS1 R enables clear visualization and complete elimination of tumors using a single and low injection dose. This study demonstrates the merits and prospects of NIR-II fluorophore with inverted polarity dependence of fluorescence quantum yield as high-performance phototheranostic agents for fluorescence imaging and phototherapy of tumors., (© 2023 Wiley-VCH GmbH.)

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion-modified metal-organic framework nanozyme (Zr 4+ -MOF-Ru 3+ /Pt 4+ -Ce6@HA, ZMRPC@HA) is designed. ZMRPC@HA with catalase (CAT) and glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME by generation of O 2 and deplete the GSH synergistically for enhancing the long-term PDT efficacy toward the hypoxic tumor. The in vitro cell inhibition and in vivo on tumor xenograft evaluations demonstrate the PDT strategy by using ZMRPC@HA can successfully inhibit the differentiation and proliferation of tumor cells under a 660 nm laser irradiation in deep tissues. These findings open a new avenue for the design of multimetallic ions functionalized MOF-based nanozymes with multienzyme mimetic activities toward the antitumor and various other biological applications., (© 2023 Wiley-VCH GmbH.)

Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H 2 O 2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn 2+ enables T 1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction., (© 2023 Wiley-VCH GmbH.)

Disease or organ damage due to unhealthy living habits, or accidents, is inevitable. Discovering an efficient strategy to address these problems is urgently needed in the clinic. In recent years, the biological applications of nanotechnology have received extensive attention. Among them, as a widely used rare earth oxide, cerium oxide (CeO 2 ) has shown good application prospects in biomedical fields due to its attractive physical and chemical properties. Here, the enzyme-like mechanism of CeO 2 is elucidated, and the latest research progress in the biomedical field is reviewed. At the nanoscale, Ce ions in CeO 2 can be reversibly converted between +3 and +4. The conversion process is accompanied by the generation and elimination of oxygen vacancies, which give CeO 2 the performance of dual redox properties. This property facilitates nano-CeO 2 to catalyze the scavenging of excess free radicals in organisms, hence providing a possibility for the treatment of oxidative stress diseases such as diabetic foot, arthritis, degenerative neurological diseases, and cancer. In addition, relying on its excellent catalytic properties, customizable life-signaling factor detectors based on electrochemical techniques are developed. At the end of this review, an outlook on the opportunities and challenges of CeO 2 in various fields is provided., (© 2023 Wiley-VCH GmbH.)

Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)-PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H 2 O 2 or O 2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Enhancing tissue permeability and achieving drug aggregation is the key to targeted tumor therapy. A series triblock copolymers of poly(ethylene glycol)-poly(L-lysine)-poly(L-glutamine) were synthesized by ring-opening polymerization, and charge-convertible nano-delivery system was constructed by loading doxorubicin (DOX) with 2-(hexaethylimide) ethanol on side chain. In normal environment (pH = 7.4), the zeta potential of the drug-loaded nanoparticle solution is negative, which is conducive to avoiding the identification and clearance of nanoparticles by the reticulo-endothelial system, while potential-reversal can be achieved in the tumor microenvironment, which effectively promotes cellular uptake. Nanoparticles could effectively reduce the distribution of DOX in normal tissues and achieve targeted aggregation at tumor sites, which can effectively improve the antitumor effect, while would not causing toxicity and damage to normal body., (© 2023. Controlled Release Society.)

Canonical phototherapeutics have several limitations, including a lack of tumor selectivity, nondiscriminatory phototoxicity, and tumor hypoxia aggravation. The tumor microenvironment (TME) is characterized by hypoxia, acidic pH, and high levels of H 2 O 2 , GSH, and proteases. To overcome the shortcomings of canonical phototherapy and achieve optimal theranostic effects with minimal side effects, unique TME characteristics are employed in the development of phototherapeutic nanomedicines. In this review, the effectiveness of three strategies for developing advanced phototherapeutics based on various TME characteristics is examined. The first strategy involves targeted delivery of phototherapeutics to tumors with the assistance of TME-induced nanoparticle disassembly or surface modification. The second strategy involves near-infrared absorption increase-induced phototherapy activation triggered by TME factors. The third strategy involves enhancing therapeutic efficacy by ameliorating TME. The functionalities, working principles, and significance of the three strategies for various applications are highlighted. Finally, possible challenges and future perspectives for further development are discussed., (© 2023 Wiley-VCH GmbH.)

In situ vaccines have revolutionized immunotherapy as they can stimulate tumor-specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Herein, a new in situ vaccine composed of acid-responsive liposome-coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell-death-induced tumor-associated antigens based on the adsorption effect of dopamine-mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long-term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy., (© 2023 Wiley-VCH GmbH.)

Background: Most microorganisms that cause food decay and the lower the shelf life of foods are fungi. Nanotechnologies can combat various diseases and deal with the application of nanomaterial to target cells or tissues. In this study selenium nanoparticles (Se-NPs) were synthesized using ascorbic acid and characterized by ultraviolet-visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction and zeta potential. The different concentrations of As/Se-NPs were tested against various fungi, including Alternaria linicola, Alternaria padwickii, Botrytis cinerea, Bipolaris sp., Cephalosporium acremonium, Fusarium moniliform and Fusarium semitectum. This study tested the influence of coated As/Se-NPs on healthy strawberry fruits and those infected with Botrytis cinerea during 16 days of storage, with regard to shelf life, decay percentage, weight loss, total titratable acidity percentage, total soluble solids content (TSS) and anthocyanin content., Results: Energy-dispersive X-ray analysis showed only two elements: selenium and oxygen. TEM images showed that the nanoparticles ranged in size between 26 to 39 nm and were rhombohedral in shape. Se-NPs showed antifungal activity against all tested fungi, the most effective being against Botrytis cinerea, Cephalosporium acremonium and Fusarium semitectum. During storage periods of strawberries fruits coated with As/Se-NPs, the shelf life was increased, and the number of decaying fruits was less than in control (uncoated) and coated infected fruits. The decline in weight loss was lower in coated fruits than in control fruits., Conclusion: These findings demonstrated that As/Se-NPs could effectively maintain the postharvest quality of strawberries, even when the fruit was infected with B. cinerea. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response., (© 2024 Wiley Periodicals LLC.)

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, t Bu-TPAD-BF 2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible t Bu-TPAD-BF 2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with t Bu-TPAD-BF 2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that t Bu-TPAD-BF 2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with t Bu-TPAD-BF 2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment., (© 2024 Wiley‐VCH GmbH.)