Diabetes mellitus is a common chronic metabolic disease, with its prevalence escalating annually. Diabetic cardiomyopathy is a leading cause of mortality among diabetic patients, characterized by intricate metabolic disturbances and myocardial cell demise. Various forms of cellular death pathways including apoptosis, pyroptosis, autophagic cell death, necroptosis, ferroptosis, and entosis have been identified in diabetic cardiomyopathy. Inhibiting myocardial cell death pathways has shown promise in mitigating diabetic cardiomyopathy progression. However, there are still gaps in understanding the role of metal ions in diabetic cardiomyopathy pathogenesis. Recent research endeavors have found that iron, copper, zinc, calcium, manganese and other metal elements related to cell death play an intricate and critical role in the pathogenesis and progression of diabetic cardiomyopathy. Notably, many animal studies have shown that the development and progression of diabetic cardiomyopathy can be alleviated by inhibiting the cell death process induced by these metal ions. Therefore, we review the molecular mechanisms underlying the death of various metal ions and the potential pathophysiological roles they play in diabetic cardiomyopathy. In addition, the value of these metal ions in the treatment of diabetic cardiomyopathy is also described.

Liver fibrosis is a progressive and fatal condition characterized by stiffness and scarring of the liver due to excessive buildup of extracellular matrix (ECM) proteins. If left untreated, it can progress to liver cirrhosis and hepatocellular carcinoma (HCC)-one of the fastest-rising causes of cancer mortality in the United States. Despite the increased prevalence of liver fibrosis due to infections, exposure to toxins, and unhealthy lifestyles, there are no effective treatments available. Recent advances in nanomedicine can lead to more targeted and effective strategies for treating liver diseases than existing treatments. In particular, the use of biomimetic nanoparticles (NPs) such as liposomes and cell-membrane-coated NPs is of interest. NPs functionalized with cell membranes mimic the properties of the source cell used and provide inherent immune evasion ability, homologous adhesion, and prolonged circulation. This review explores the types of biomimetic coatings, different cargoes delivered through biomimetic NPs for various treatment modalities, and the type of core NPs used for targeting liver fibrosis and HCC.

Conventional cancer treatments often have complications and serious side effects, with limited improvements in 5-year survival and quality of life. Photothermal therapy (PTT) employs materials that convert light to heat when exposed to near-infrared light to raise the temperature of the tumor site to directly ablate tumor cells, induce immunogenic cell death, and improve the tumor microenvironment. This therapy has several benefits, including minimal invasiveness, high efficacy, reduced side effects, and robust targeting capabilities. Beyond just photothermal conversion materials, nanoplatforms significantly contribute to PTT by supplying effective photothermal conversion materials and bolstering tumor targeting to amplify anti-tumor effects. However, the anti-tumor effects of PTT alone are ultimately limited and often need to be combined with other therapies. This narrative review describes the recent progress of PTT combined with chemotherapy, radiotherapy, photodynamic therapy, immunotherapy, gene therapy, gas therapy, chemodynamic therapy, photoacoustic imaging, starvation therapy, and multimodal therapy. Studies have shown that combining PTT with other treatments can improve efficacy, reduce side effects, and overcome drug resistance. Despite the encouraging results, challenges such as optimizing treatment protocols, addressing tumor heterogeneity, and overcoming biological barriers remain. This paper highlights the potential for personalized, multimodal approaches to improve cancer treatment outcomes.

Liver cancer is a highly lethal malignant tumor with a high incidence worldwide. Therefore, its treatment has long been a focus of medical research. Although traditional treatment methods such as surgery, radiotherapy, and chemotherapy have increased the survival rate of patients, their efficacy remains unsatisfactory owing to the nonspecific distribution of drugs, high toxicity, and drug resistance of tumor tissues. In recent years, the application of nanotechnology in the medical field has opened a new avenue for the treatment of liver cancer. Among these treatment methods, photothermal therapy (PTT) based on nanoliposomes has attracted wide attention owing to its unique targeting and high efficiency. This article reviews the latest preclinical research progress of nanoliposome-based PTT for liver cancer and its metastasis, discusses the preclinical challenges in this field, and proposes directions for improvement, with the aim of improving the effectiveness of liver cancer treatment.

Copper, an essential trace element, is integral to numerous metabolic pathways across biological systems. In recent years, copper-based biomaterials have garnered significant interest due to their superior biocompatibility and multifaceted functionalities, particularly in the treatment of malignancies such as sarcomas and cancers. On the one hand, these copper-based materials serve as efficient carriers for a range of therapeutic agents, including chemotherapeutic drugs, small molecule inhibitors, and antibodies, allowing them for precise delivery and controlled release triggered by specific modifications and stimuli. On the other hand, they can induce cell death through mechanisms such as ferroptosis, cuproptosis, apoptosis, and pyroptosis, or inhibit the proliferation and invasion of cancer cells via their outstanding properties. Furthermore, advanced design approaches enable these materials to support tumor imaging and immune activation. Despite this progress, the full scope of their functional capabilities remains to be fully elucidated. This review provides an overview of the anti-tumor functions, underlying mechanisms, and design strategies of copper-based biomaterials, along with their advantages and limitations. The aim is to provide insights into the design, study, and development of novel multifunctional biomaterials, with the ultimate goal of accelerating the clinical application of copper-based nanomaterials in cancer therapy. STATEMENT OF SIGNIFICANCE: This study explores the groundbreaking potential of copper-based biomaterials in cancer therapy, uniquely combining biocompatibility with diverse therapeutic mechanisms such as targeted drug delivery and inhibition of cancer cells through specific cell death pathways. By enhancing tumor imaging and immune activation, copper-based nanomaterials have opened new avenues for cancer treatment. This review examines these multifunctional biomaterials, highlighting their advantages and current limitations while addressing gaps in existing research. The findings aim to accelerate clinical applications of these materials in the field of oncology, providing valuable insights for the design of next-generation copper-based therapies. Therefore, this work is highly relevant to researchers and practitioners focused on innovative cancer treatments.

Macrophage is an important component in the tumor immune microenvironment, which exerts significant influence on tumor development and metastasis. Due to their dual nature of promoting and suppressing inflammation, macrophages can serve as both targets for tumor immunotherapy and tools for treating malignancies. However, the abundant infiltration of tumor-associated macrophages dominated by an immunosuppressive phenotype maintains a pro-tumor microenvironment, and engineering macrophages using nanotechnology to manipulate the tumor immune microenvironment represent a feasible approach for cancer immunotherapy. Additionally, considering the phagocytic and specifically tumor-targeting capabilities of M1 macrophages, macrophages manipulated through cellular engineering and nanotechnology, as well as macrophage-derived exosomes and macrophage membranes, can also become effective tools for cancer treatment. In conclusion, nanotherapeutics targeting macrophages remains immense potential for the development of macrophage-mediated tumor treatment methods and will further enhance our understanding, diagnosis, and treatment of various malignants.

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application in repressing cancer progression. Traditional cancer vaccines containing a single or a few discrete tumor epitopes have failed in the clinic, possibly due to challenges in epitope selection, target downregulation, cancer cell heterogeneity, tumor microenvironment immunosuppression, or a lack of vaccine immunogenicity. Whole cancer cell or cancer membrane vaccines, which provide a rich source of antigens, are emerging as viable alternatives. Autologous and allogenic cellular cancer vaccines have been evaluated as clinical treatments. Tumor cell membranes (TCMs) are an intriguing antigen source, as they provide membrane-accessible targets and, at the same time, serve as integrated carriers of vaccine adjuvants and other therapeutic agents. This review provides a summary of the properties and technologies for TCM cancer vaccines. Characteristics, categories, mechanisms, and preparation methods are discussed, as are the demonstrable additional benefits derived from combining TCM vaccines with chemotherapy, sonodynamic therapy, phototherapy, and oncolytic viruses. Further research in chemistry, biomedicine, cancer immunology, and bioinformatics to address current drawbacks could facilitate the clinical adoption of TCM vaccines.

Low tumor enrichment remains a serious and urgent problem for drug delivery in cancer therapy. Accurate targeting of tumor sites is still a critical aim in cancer therapy. Though there have been a variety of delivery strategies to improve the tumor targeting and enrichment, biological barriers still cause most delivered guests to fail or be excreted before they work. Recently, cell membrane-based systems have attracted a huge amount of attention due to their advantages such as easy access, good biocompatibility and immune escape, which contribute to their biomimetic structures and specific surface proteins. Furthermore, cancer cell membrane-based delivery systems are referred to as homologous-targeting function in which they exhibit significantly high adhesion and internalization to homologous-type tumor sites or cells even though the exact mechanism is not entirely revealed. Here, we summarize the sources and characterizations of cancer cell membrane systems, including reconstructed single or hybrid membrane-based nano-/microcarriers, as well as engineered cancer cells. Additionally, advanced applications of these cancer cell membrane systems in cancer therapy are categorized and summarized according to the components of membranes. The potential factors related to homologous targeting of cancer cell membrane-based systems are also discussed. By discussing the applications, challenges and opportunities, we expect the cancer cell membrane-based homologous-targeting systems to have a far-reaching development in preclinic or clinics.

Nanoparticles can enhance drugs accumulating at the tumor site and hold tremendous promise for achieving effective tumor treatment. However, due to the complexity of cancer heterogeneity and suppressive tumor microenvironment, the delivery of traditional nanoparticles has poor infiltration and off-target effects, making it difficult to control the drug release rate and causing off-target toxicity. In recent years, cell membrane-coated biomimetic nanoparticles have been developed, which have both the natural characteristics of biomembranes and the physical characteristics of traditional nanoparticles, thus improving the homologous targeting ability of nanoparticles to tumor cells and better biocompatibility. In this paper, we reviewed the application of single cell membrane and hybrid cell membrane-coated biomimetic nanoparticles in the integration for tumor diagnosis and treatment. We talked about the preparation methods of cell membrane-coated nanoparticles, the targeting mechanisms, and the effects of imaging and therapeutic outcomes of different cell membrane-coated biomimetic nanoparticles in detail. Finally, we discussed the existing problems and prospects of cell membrane-coated biomimetic nanomaterials.

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

The technique of engineering drug delivery vehicles continues to develop, which bring enhancements in working more efficiently and minimizing side effects to make it more effective and safer. The intense capability of therapeutic agents to remain undamaged in a harsh extracellular environment is helpful to the success of drug development efforts. With this in mind, alterations of biopharmaceuticals with enhanced stability and decreased immunogenicity have been an increasingly active focus of such efforts. Red blood cells (RBCs), also known as erythrocytes have undergone extensive scrutiny as potential vehicles for drug delivery due to their remarkable attributes over the years of research. These include intrinsic biocompatibility, minimal immunogenicity, flexibility, and prolonged systemic circulation. Throughout the course of investigation, a diverse array of drug delivery platforms based on RBCs has emerged. These encompass genetically engineered RBCs, non-genetically modified RBCs, and RBC membrane-coated nanoparticles, each devised to cater to a range of biomedical objectives. Given their prevalence in the circulatory system, RBCs have gained significant attention for their potential to serve as biomimetic coatings for artificial nanocarriers. By virtue of their surface emulation capabilities and customizable core materials, nanocarriers mimicking these RBCs, hold considerable promise across a spectrum of applications, spanning drug delivery, imaging, phototherapy, immunomodulation, sensing, and detection. These multifaceted functionalities underscore the considerable therapeutic and diagnostic potential across various diseases. Our proposed review provides the synthesis of recent strides in the theranostic utilization of erythrocytes in the context of cancer. It also delves into the principal challenges and prospects intrinsic to this realm of research. The focal point of this review pertains to accentuating the significance of erythrocyte-based theranostic systems in combating cancer. Furthermore, it precisely records the latest and the most specific methodologies for tailoring the attributes of these biomimetic nanoscale formulations, attenuating various discoveries for the treatment and management of cancer.

The emerging strategy of biomimetic nanoparticles (NPs) via cellular membrane camouflage holds great promise in cancer therapy. This scholarly review explores the utilization of cellular membranes derived from diverse cellular entities; blood cells, immune cells, cancer cells, stem cells, and bacterial cells as examples of NP coatings. The camouflaging strategy endows NPs with nuanced tumor-targeting abilities such as self-recognition, homotypic targeting, and long-lasting circulation, thus also improving tumor therapy efficacy overall. The comprehensive examination encompasses a variety of cell membrane camouflaged NPs (CMCNPs), elucidating their underlying targeted therapy mechanisms and delineating diverse strategies for anti-cancer applications. Furthermore, the review systematically presents the synthesis of source materials and methodologies employed in order to construct and characterize these CMCNPs, with a specific emphasis on their use in cancer treatment.

Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by an exceedingly high recurrence rate post-surgery, significantly impairing the prognosis of HCC patients. However, a standard in-care strategy for postoperative therapy is still lacking. Although encouraging results have been obtained in a newly published clinical trial for postoperative therapy by targeting the vascular endothelial growth factor (VEGF) and programmed death ligand 1 (anti-PD-L1), its efficacy remains constrained. Combining a hemostatic hydrogel with a nanoparticle-based drug delivery system presents an opportunity to optimize the antitumor effect. Herein, we developed a nanoplatform, termed HMSN@Sor/aP@Gel, comprising a hemostatic fibrin hydrogel and functionalized hollow mesoporous silica nanoparticles (HMSNs) loaded with sorafenib and anti-PD-L1 for locally administered targeted-immunotherapy to prevent the postoperative recurrence and metastasis of HCC. The antitumor mechanism is grounded in dual inhibition of Ras/Raf/MEK/ERK (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathways, synergistically complemented by PD-L1 blockade. HMSN@Sor/aP@Gel facilitates dendritic cell maturation, enhances cytotoxic T-lymphocyte infiltration, promotes the polarization of tumor-associated macrophages to M1 phenotype, induces tumor immunogenic cell death, reverses immunosuppression, and establishes immune memory to counter postoperative recurrence. Animal studies corroborate that HMSN@Sor/aP@Gel-mediated targeted immunotherapy significantly impedes primary and metastatic tumor growth and establishes immune memory to prevent recurrence post-surgery. This investigation presents a promising strategy for postoperative therapy with considerable potential for clinical translation.

The role of macrophages in regulating the tumor microenvironment has spurned the exponential generation of nanoparticle targeting technologies. With the large amount of literature and the speed at which it is generated it is difficult to remain current with the most up-to-date literature. In this study we performed a topic modeling analysis of 854 abstracts of peer-reviewed literature for the most common usages of nanoparticle targeting of tumor associated macrophages (TAMs) in solid tumors. The data spans 20 years of literature, providing a broad perspective of the nanoparticle strategies. Our topic model found 6 distinct topics: Immune and TAMs, Nanoparticles, Imaging, Gene Delivery and Exosomes, Vaccines, and Multi-modal Therapies. We also found distinct nanoparticle usage, tumor types, and therapeutic trends across these topics. Moreover, we established that the topic model could be used to assign new papers into the existing topics, thereby creating a Living Review. This type of "birds-eye-view" analysis provides a useful assessment tool for exploring new and emerging themes within a large field.

The treatment of digestive system tumors presents challenges, particularly in immunotherapy, owing to the advanced immune tolerance of the digestive system. Nanomaterials have emerged as a promising approach for addressing these challenges. They provide targeted drug delivery, enhanced permeability, high bioavailability, and low toxicity. Additionally, nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment (TIME). Among the various cells in the TIME, tumor-associated macrophages (TAMs) are the most abundant and play a crucial role in tumor progression. Therefore, investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance. Here, we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer. We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system. Furthermore, this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors. Overall, this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems have shown promise in solving problems associated with the distribution of hydrophobic drugs and have promoted the accumulation of nanomedicines in the circulation or in organs. However, the injection dose of nanoparticles (NPs) is much greater than that needed by diseased tissues or organs. In other words, most of the NPs are localized off-target and do not reach the desired tissue or organs. With the rapid development of biodegradable and biosafety nanomaterials, the nanovectors represent assurance of safety. However, the off-target effects also induce concerns about the application of NPs, especially in the delivery of gene editing tools. Therefore, a complete understanding of the biological responses to NPs in the body will clearly guide the design of targeted delivery of NPs. The different properties of various nanodelivery systems may induce diverse interactions between carriers and organs. In this review, we describe the relationship between the liver, the most influenced organ of systemic administration of NPs, and targeted delivery nanoplatforms. Various transport vehicles have adopted multiple delivery strategies for the targeted delivery to the cells in the homeostasis liver and in diseased liver. Additionally, nanodelivery systems provide a novel strategy for treating incurable diseases. The appearance of a targeted delivery has profoundly improved the application of NPs to liver diseases.

Cell division cyclin 25C (CDC25C) is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that CDC25C could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.

To explore the impact of CDC25C on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development.

Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV-CDC25C shRNA) to knock down CDC25C. Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo. Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting.

CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction. A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice. CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells.

The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.

Nanoparticle-based drug delivery systems hold promise for cancer treatment by enhancing the solubility and stability of anti-tumor drugs. Nonetheless, the challenges of inadequate targeting and limited biocompatibility persist. In recent years, cell membrane nano-biomimetic drug delivery systems have emerged as a focal point of research and development, due to their exceptional traits, including precise targeting, low toxicity, and good biocompatibility. This review outlines the categorization and advantages of cell membrane bionic nano-delivery systems, provides an introduction to preparation methods, and assesses their applications in cancer treatment, including chemotherapy, gene therapy, immunotherapy, photodynamic therapy, photothermal therapy, and combination therapy. Notably, the review delves into the challenges in the application of various cell membrane bionic nano-delivery systems and identifies opportunities for future advancement. Embracing cell membrane-coated biomimetic nanoparticles presents a novel and unparalleled avenue for personalized tumor therapy.

Hepatocellular carcinoma (HCC) has become an important public health problem, and there are still challenges to overcome in clinical treatment. The nanodrug delivery system (NDDS) has developed tremendously in recent years, and many researchers have explored NDDS for the treatment of HCC. Engineered cell membrane-coated nanoparticles (ECNPs) have emerged, combining the unique functions of cell membranes with the engineering versatility of synthetic nanoparticles (NPs) to effectively deliver therapeutic drugs. It is designed to have the capabilities: specific active targeting, immune evasion, prolonging the circulation blood time, controlled drug release delivery, and reducing drugs systematic toxicity. Thus, ECNPs are a promising bionic tool in the treatment of HCC and have operability to achieve combination and integrated therapy. This review focuses on the mechanism and strategy of ECNPs for the treatment of HCC and summarizes its research progress in the treatment of HCC in recent years.

Nano-biointerfaces play a pivotal role in determining the functionality of engineered therapeutic nanoparticles, particularly in the context of designing nanovaccines to effectively activate immune cells for cancer immunotherapy. Unlike involving chemical reactions by conventional surface decorating strategies, cell membrane-coating technology offers a straightforward approach to endow nanoparticles with natural biosurfaces, enabling them to mimic and integrate into the intricate biosystems of the body to interact with specific cells under physiological conditions. In this study, cell membranes, in a hybrid formulation, derived from cancer and activated macrophage cells were found to enhance the interaction of nanoparticles (HMP) with dendritic cells (DCs) and T cells among the mixed immune cells from lymph nodes (LNs), which could be leveraged in the development of nanovaccines for anti-tumor therapy. After loading with an adjuvant (R837), the nanoparticles coated with a hybrid membrane (HMPR) demonstrated effectiveness in priming DCs both in vitro and in vivo, resulting in amplified anti-tumor immune responses compared to those of nanoparticles coated with a single type of membrane or those lacking a membrane coating. The elevated immunoactivity of nanoparticles achieved by incorporating a hybrid membrane biosurface provides us a more profound comprehension of the nano-immune interaction, which may significantly benefit the development of bioactive nanomaterials for advanced therapy.

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.

Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns. Researchers combine photosensitisers or photothermal agents with natural cell membranes to overcome these obstacles to create a nano biomimetic therapeutic platform. When used to coat nanoparticles, red blood cells, platelets, cancer cells, macrophages, lymphocytes, and bacterial outer membranes could provide prolonged circulation, tumour targeting, immune stimulation, or antigenicity. This article covers the principles of cellular membrane biomimetic nanotechnology and phototherapy, along with recent advancements in applying nano biomimetic technology to PDT, PTT, PCT, and combined diagnosis and treatment. Furthermore, the challenges and issues of using nano biomimetic nanoparticles in phototherapy are discussed. STATEMENT OF SIGNIFICANCE: Currently, there has been significant progress in the field of cell membrane biomimetic technology. Researchers are exploring its potential application in tumor diagnosis and treatment through phototherapy. Scholars have conducted extensive research on combining cell membrane technology and phototherapy in anticancer diagnosis and treatment. This review aims to highlight the mechanisms of phototherapy and the latest advancements in single phototherapy (PTT, PDT) and combination phototherapy (PCT, PRT, and PIT), as well as diagnostic approaches. The review provides an overview of various cell membrane technologies, including RBC membranes, platelet membranes, macrophage cell membranes, tumour cell membranes, bacterial membranes, hybrid membranes, and their potential for anticancer applications under phototherapy. Lastly, the review discusses the challenges and future directions in this field.

Conventional cancer mono-therapeutic approaches including radiotherapy, surgery, and chemotherapy don't always achieve satisfactory outcomes and are frequently associated with significant limitations. Although chemotherapy is a vital intervention, its effectiveness is frequently inadequate and is associated with metastasis, multidrug resistance, off-target effect, and normal cells toxicity. Phototherapies are employed in cancer therapy, encompassing photo-dynamic and photo-thermal therapies which under favorable NIR laser light irradiation initiate the included photosensitizers and photo-thermal agents to generate ROS or thermal heat respectively for cancer cells destruction. Photo-therapy is considered noninvasive, posing no resistance, but it still suffers from several pitfalls like low penetration depth and excessive heat generation affecting neighboring tissues. Improved selectivity and tumor-homing capacity could be attained through surface modulation of nanoparticles with targeting ligands that bind to receptors, which are exclusively overexpressed on cancerous cells. Developing novel modified targeted nanoparticulate platforms integrating different therapeutic modalities like photo-therapy and chemotherapy is a topic of active research. This review aimed to highlight recent advances in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers for smart combinatorial chemotherapy/photo-therapy. Nanocarriers decorated with precise targeting ligands, like aptamers, antibody, and lactoferrin, to achieve active tumor-targeting or camouflaging using various biological cell membrane coating are designed to achieve homologous tumor-targeting.

In recent years, considerable attention has been given to phototherapy, including photothermal and photodynamic therapy to kill tumor cells by producing heat or reactive oxygen species (ROS). It has the high merits of noninvasiveness and limited drug resistance. To fully utilize this therapy, an extraordinary nanovehicle is required to target phototherapeutic agents in the tumor cells. Nanovesicles embody an ideal strategy for drug delivery applications. Cell membrane-derived biomimetic nanovesicles represent a developing type of nanocarrier. Combining this technique with cancer phototherapy could enable a novel strategy. Herein, efforts are made to describe a comprehensive overview of cell membrane-derived biomimetic nanovesicles for cancer phototherapy. The description in this review is mainly based on representative examples of exosome-derived biomimetic nanomedicine research, ranging from their comparison with traditional nanocarriers to extensive applications in cancer phototherapy. Additionally, the challenges and future prospectives for translating these for clinical application are discussed.

Studies have reported on the significance of copper incorporated nanomaterials (CINMs) in cancer theranostics and tissue regeneration. Given their unique physicochemical properties and tunable nanostructures, CINMs are used in photothermal therapy (PTT) and photothermal-derived combination therapies. They have the potential to overcome the challenges of unsatisfactory efficacy of conventional therapies in an efficient and non-invasive manner. This review summarizes the recent advances in CINMs-based PTT in biomedicine. First, the classification and structure of CINMs are introduced. CINMs-based PTT combination therapy in tumors and PTT guided by multiple imaging modalities are then reviewed. Various representative designs of CINMs-based PTT in bone, skin and other organs are presented. Furthermore, the biosafety of CINMs is discussed. Finally, this analysis delves into the current challenges that researchers face and offers an optimistic outlook on the prospects of clinical translational research in this field. This review aims at elucidating on the applications of CINMs-based PTT and derived combination therapies in biomedicine to encourage future design and clinical translation.

Nanomedicine presents innovative solutions for cancer treatment, including photothermal therapy (PTT). PTT centers on the design of photoactivatable nanoparticles capable of absorbing non-toxic near-infrared light, generating heat within target cells to induce cell death. The successful transition from benchside to bedside application of PTT critically depends on the core properties of nanoparticles responsible for converting light into heat and the surface properties for precise cell-specific targeting. Precisely targeting the intended cells remains a primary challenge in PTT. In recent years, a groundbreaking approach has emerged to address this challenge by functionalizing nanocarriers and enhancing cell targeting. This strategy involves the creation of biomimetic nanoparticles that combine desired biocompatibility properties with the immune evasion mechanisms of natural materials. This review comprehensively outlines various strategies for designing biomimetic photoactivatable nanocarriers for PTT, with a primary focus on its application in cancer therapy. Additionally, we shed light on the hurdles involved in translating PTT from research to clinical practice, along with an overview of current clinical applications.

Tumor cells may be eliminated by increasing their temperature. This is achieved via photothermal therapy (PTT) by penetrating the tumor tissue with near-infrared light and converting light energy into heat using photothermal agents. Copper sulfide nanoparticles (CuS NPs) are commonly used as PTAs in PTT. In this review, we aimed to discuss the synergism between tumor PTT with CuS NPs and other therapies such as chemotherapy, radiotherapy, dynamic therapies (photodynamic, chemodynamic, and sonodynamic therapy), immunotherapy, gene therapy, gas therapy, and magnetic hyperthermia. Furthermore, we summarized the results obtained with a combination of two treatments and at least two therapies, with PTT as one of the included therapies. Finally, we summarized the benefits and drawbacks of various therapeutic options and state of the art CuS-based PTT and provided future directions for such therapies.

Hepatocellular carcinoma (HCC) is one of the cancers that has the highest morbidity and mortality rates. In clinical practice, there are still many limitations in surveilling, diagnosing, and treating HCC, such as the poor detection of early HCC, the frequent post-surgery recurrence, the low local tumor control rate, the therapy resistance and side effects. Therefore, improved, or innovative modalities are urgently required for early diagnosis as well as refined and effective management. In recent years, nanotechnology research in the field of HCC has received great attention, with various aspects of diagnosis and treatment including biomarkers, ultrasound, diagnostic imaging, intraoperative imaging, ablation, transarterial chemoembolization, radiotherapy, and systemic therapy. Different from previous reviews that discussed from the perspective of nanoparticles' structure, design and function, this review systematically summarizes the methods and limitations of diagnosing and treating HCC in clinical guidelines and practices, as well as nanomedicine applications. Nanomedicine can overcome the limitations to improve diagnosis accuracy and therapeutic effect via enhancement of targeting, biocompatibility, bioavailability, controlled releasing, and combination of different clinical treatment modalities. Through an in-depth understanding of the logic of nanotechnology to conquer clinical limitations, the main research directions of nanotechnology in HCC are sorted out in this review. It is anticipated that nanomedicine will play a significant role in the future clinical practices of HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death worldwide. Conventional treatments for HCC include drugs, radiation, and surgery. Despite the unremitting efforts of researchers, the curative effect of HCC has been greatly improved, but because HCC is often found in the middle and late stages, the curative effect is still not satisfactory, and the 5-year survival rate is still low. Nanomedicine is a potential subject, which has been applied to the treatment of HCC and has achieved promising results. Here, we summarized the factors affecting the efficacy of drugs in HCC treatment and the strategies for improving the efficacy of nanotechnology-based drugs in HCC, reviewed the recent applications' progress on nanotechnology-based drugs in HCC treatment, and discussed the future perspectives and challenges of nanotechnology-based drugs in HCC treatment.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Thermal therapy has been widely used in clinical tumor treatment and more recently in combination with chemotherapy, where the key challenge is the treatment resistance. The mechanism at the cellular level underlying the resistance to thermo-chemical combination therapy remains elusive. In this study, we constructed 3D culture models for glioma cells (i.e., 3D glioma spheres) as the model system to recapitulate the native tumor microenvironment and systematically investigated the thermal response of 3D glioma spheres at different hyperthermic temperatures. We found that 3D glioma spheres show high viability under hyperthermia, especially under high hyperthermic temperatures (42 °C). Further study revealed that the main mechanism lies in the high energy level of cells in 3D glioma spheres under hyperthermia, which enables the cells to respond promptly to thermal stimulation and maintain cellular viability by upregulating the chaperon protein Hsp70 and the anti-apoptotic pathway AKT. Besides, we also demonstrated that 3D glioma spheres show strong drug resistance to the thermo-chemical combination therapy. This study provides a new perspective on understanding the thermal response of combination therapy for tumor treatment.

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.

The role of macrophages in regulating the tumor microenvironment has spurned the exponential generation of nanoparticle targeting technologies. With the large amount of literature and the speed at which it is generated it is difficult to remain current with the most up-to-date literature. In this study we performed a topic modeling analysis of the most common usages of nanoparticle targeting of macrophages in solid tumors. The data spans 20 years of literature, providing an extensive meta-analysis of the nanoparticle strategies. Our topic model found 6 distinct topics: Immune and TAMs, Nanoparticles, Imaging, Gene Delivery and Exosomes, Vaccines, and Multi-modal Therapies. We also found distinct nanoparticle usage, tumor types, and therapeutic trends across these topics. Moreover, we established that the topic model could be used to assign new papers into the existing topics, thereby creating a Living Review. This type of meta-analysis provides a useful assessment tool for aggregating data about a large field.

Management of cancer metastasis has been associated with remarkable reduction in progression of cancer cells and improving survival rate of patients. Since 90% of mortality are due to cancer metastasis, its suppression can improve ability in cancer fighting. The EMT has been an underlying cause in increasing cancer migration and it is followed by mesenchymal transformation of epithelial cells. HCC is the predominant kind of liver tumor threatening life of many people around the world with poor prognosis. Increasing patient prognosis can be obtained via inhibiting tumor metastasis. HCC metastasis modulation by EMT and HCC therapy by nanoparticles are discussed here. First of all, EMT happens during progression and advanced stages of HCC and therefore, its inhibition can reduce tumor malignancy. Moreover, anti-cancer compounds including all-trans retinoic acid and plumbaging, among others, have been considered as inhibitors of EMT. The EMT association with chemoresistance has been evaluated. Moreover, ZEB1/2, TGF-β, Snail and Twist are EMT modulators in HCC and enhancing cancer invasion. Therefore, EMT mechanism and related molecular mechanisms in HCC are evaluated. The treatment of HCC has not been only emphasized on targeting molecular pathways with pharmacological compounds and since drugs have low bioavailability, their targeted delivery by nanoparticles promotes HCC elimination. Moreover, nanoparticle-mediated phototherapy impairs tumorigenesis in HCC by triggering cell death. Metastasis of HCC and even EMT mechanism can be suppressed by cargo-loaded nanoparticles.

Hepatocellular carcinoma (HCC), the most common liver malignancy with a poor prognosis and increasing incidence, remains a serious health problem worldwide. Immunotherapy has been described as one of the ideal ways to treat HCC and is transforming patient management. However, the occurrence of immunotherapy resistance still prevents some patients from benefiting from current immunotherapies. Recent studies have shown that histone deacetylase inhibitors (HDACis) can enhance the efficacy of immunotherapy in a variety of tumors, including HCC. In this review, we present current knowledge and recent advances in immunotherapy-based and HDACi-based therapies for HCC. We highlight the fundamental dynamics of synergies between immunotherapies and HDACis, further detailing current efforts to translate this knowledge into clinical benefits. In addition, we explored the possibility of nano-based drug delivery system (NDDS) as a novel strategy to enhance HCC treatment.

Integrins are heterodimeric transmembrane proteins that mediate adhesive connections between cells and their surroundings, including surrounding cells and the extracellular matrix (ECM). They modulate tissue mechanics and regulate intracellular signaling, including cell generation, survival, proliferation, and differentiation, and the up-regulation of integrins in tumor cells has been confirmed to be associated with tumor development, invasion, angiogenesis, metastasis, and therapeutic resistance. Thus, integrins are expected to be an effective target to improve the efficacy of tumor therapy. A variety of integrin-targeting nanodrugs have been developed to improve the distribution and penetration of drugs in tumors, thereby, improving the efficiency of clinical tumor diagnosis and treatment. Herein, we focus on these innovative drug delivery systems and reveal the improved efficacy of integrin-targeting methods in tumor therapy, hoping to provide prospective guidance for the diagnosis and treatment of integrin-targeting tumors.

In recent years, there have been many exciting developments in the biomedical applications of the macrophage membrane bionic drug delivery system (MM-Bio-DDS). Macrophages, as an important immune cell, are involved in initiating and regulating the specific immune response of the body. Therefore, the inflammatory process related to macrophages is an important goal in the diagnosis and treatment of many diseases. In this review, we first summarise the different methods of preparation, characterisation, release profiles and natural advantages of using macrophages as a drug delivery system (DDS). Second, we introduce the processes of various chronic inflammatory diseases and the role of macrophages in them, specifically clarifying how the MM-Bio-DDS provides a wide and effective treatment for the targeted inflammatory site. Finally, based on the existing research, we propose the application prospect and existing challenges of the MM-Bio-DDS, especially the problems in clinical transformation, to provide new ideas for the development and utilisation of the MM-Bio-DDS in targeted drug delivery for inflammation and the treatment of diseases.

Immune clearance and insufficient targeting have limited the efficacy of existing therapeutic strategies for cancer. Toxic side effects and individual differences in response to treatment have further limited the benefits of clinical treatment for patients. Biomimetic cancer cell membrane-based nanotechnology has provided a new approach for biomedicine to overcome these obstacles. Biomimetic nanoparticles exhibit various effects (e.g., homotypic targeting, prolonging drug circulation, regulating the immune system, and penetrating biological barriers) after encapsulation by cancer cell membranes. The sensitivity and specificity of diagnostic methods will also be improved by utilizing the properties of cancer cell membranes. In this review, different properties and functions of cancer cell membranes are presented. Utilizing these advantages, nanoparticles can exhibit unique therapeutic capabilities in various types of diseases, such as solid tumors, hematological malignancies, immune system diseases, and cardiovascular diseases. Furthermore, cancer cell membrane-encapsulated nanoparticles show improved effectiveness and efficiency in combination with current diagnostic and therapeutic methods, which will contribute to the development of individualized treatments. This strategy has promising clinical translation prospects, and the associated challenges are discussed.

The slightest change in the extra/intracellular concentration of metal ions results in amplified effects by signaling cascades that regulate both cell fate within the tumor microenvironment and immune status, which influences the network of antitumor immunity through various pathways. Based on the fact that metal ions influence the fate of cancer cells and participate in both innate and adaptive immunity, they are widely applied in antitumor therapy as immune modulators. Moreover, nanomedicine possesses the advantage of precise delivery and responsive release, which can perfectly remedy the drawbacks of metal ions, such as low target selectivity and systematic toxicity, thus providing an ideal platform for metal ion application in cancer treatment. Emerging evidence has shown that immunotherapy applied with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus on the physiopathology of metal ions in tumorigenesis and discuss several breakthroughs regarding the use of nanometallic materials in antitumor immunotherapeutics. These findings demonstrate the prominence of metal ion-based nanomedicine in cancer therapy and prophylaxis, providing many new ideas for basic immunity research and clinical application. Consequently, we provide innovative insights into the comprehensive understanding of the application of metal ions combined with nanomedicine in cancer immunotherapy in the past few years.

Multifunctional core-shell hybrids formed by integration of metal-organic framework (MOF) and functional materials have attracted extensive attention as promising theranostic nanoplatforms due to their combined novel properties and enhanced therapeutic efficacy. Recently, the second near-infrared (NIR-II, 1000-1700 nm) laser-induced photothermal therapy (PTT) as compared to the NIR-I(700-950 nm) laser-induced PTT has displayed improved therapeutic effects owing to its merits that include deeper tissue penetration and increased maximum permissible exposure. Herein, a novel core-shell hollow copper sulfide@metal-organic framework (HCuS@MIL-100) has been successfully fabricated by a layer-by-layer technique for the first time and their collective theranostic effects are investigated in vitro and in vivo. In this platform, the inner HCuS was applied as the NIR-II photothermal agent with excellent NIR-II absorption feature, leading to impressive photothermal effects under irradiation by 1064 nm light. With MIL-100 as the shell, HCuS@MIL-100 not only displayed optimal biocompatibility but also presented superior T2 magnetic resonance imaging (MRI) ability. In the current study multifunctional hollow core-shell HCuS@MIL-100 are fabricated for the MRI-guided PTT. This study also offers a facile and effective strategy for the development of novel theranostic platforms with high efficiency through the integration of MOFs and functional materials.

Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.