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Immunotherapy offers a promising avenue for reducing tumor metastasis and recurrence but faces challenges from the tumor immunosuppressive microenvironment (TIME) and restricted antigen presentation. To address these challenges, this study have developed an innovative approach utilizing molybdenum (Mo)‐doped Prussian blue nanoparticles coated with a cancer cell membrane (CCM), referred to as PMo@CCM. This novel nanoplatform excels in performing photothermal therapy (PTT), while the Mo and Fe components effectively deplete glutathione (GSH) and generate reactive oxygen species (ROS), thereby significantly enhancing chemodynamic therapy (CDT) and remodeling the TIME. The synergistic PTT/CDT approach not only induces tumor immunogenic cell death (ICD) but also facilitates antigen presentation. The CCM coating further supplies antigens and prompts dendritic cell (DC) maturation. This comprehensive strategy markedly enhances the effectiveness of immunotherapy, as evidenced by a significant increase in T cell activation. Moreover, the use of programmed cell death protein 1 antibodies (anti PD‐1) effectively blocks the PD‐1 immune checkpoint pathway. RNA sequencing analysis has identified genes associated with the observed substantial reduction in tumor growth. In conclusion, the PMo@CCM nanoplatform enables homologously targeted tumor synergistic therapy, guided by photothermal and magnetic resonance imaging (PTI&MRI), significantly impeding the progression of both primary and metastatic tumors. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA 257–264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA 257–264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA 257–264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug delivery nanosystems can effectively enhance the efficiency of drugs in the treatment process. However, traditional drug delivery nanosystems suffer from easy clearance by the immune system, lack of targeting, and nonresponsive drug release. Herein, we designed a biomimetic hollow manganese dioxide (H-MnO2) nanocarrier, which is coated with the homologous cell membrane and enables pH-controlled release in the tumor microenvironment (TME), to deliver sorafenib (SOR) for targeted diagnosis and treatment of liver cancer. The coated hepatoma cell membrane gives SOR-loaded H-MnO2 good immune evasion ability, enabling it to reach tumor cells smoothly and rapidly degrade and release SOR in the TME. During this process, Mn2+ resulting from H-MnO2 degradation can also be subjected to T1-weighted magnetic resonance imaging (MRI). Furthermore, compared with free SOR and nontargeted H-MnO2–SOR nanoparticles, CM–H-MnO2–SOR was proved by in vitro cell experiments to be more easily ingested by hepatoma cells. This result shows better targeting of hepatoma cells and strong immune escape ability, therefore significantly inhibiting the growth of hepatoma cells and improving the apoptosis rate. In vivo animal experiments show that CM–H-MnO2–SOR has good MRI ability, excellent tumor treatment effect, and high biological safety. In total, we believe all these advantages would make CM–H-MnO2–SOR an ideal choice for hepatocellular carcinoma (HCC) diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H 2 O 2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H 2 O 2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H 2 O 2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Immune cells distinguish cancer cells mainly relying on their membrane-membrane communication. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. We exploit cancer cell membranes as the whole cancer antigen repertoire and reinforce its immunogenicity by cellular engineering to modulate the cytomembrane's immune-associated functions. This study reports a vaccine platform based on radiation-engineered cancer cells, of which the membrane HSP70 protein as the immune chaperon/traitor is endogenously upregulated. The resulting positive influences are shown to cover immunogenic steps occurring in antigen-presenting cells, including the uptake and the cross-presentation of the cancer antigens, thus amplifying cancer-specific immunogenicity. Membrane vaccines offer chances to introduce desired metal ions through membrane-metal complexation. Using Mn2+ ion as the costimulatory interferon genes agonist, immune activity is enhanced to further boost adaptive cancer immunogenicity. Results have evidenced that this artificially engineered membrane vaccine with favorable bio-safety could considerably reduce tumorigenicity and inhibit tumor growth. This study provides a universally applicable and facilely available cancer vaccine platform by artificial engineering of cancer cells to inherit and amplify the natural merits of cancer cell membranes. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. Cancer cell membrane presents superior advantages as the whole cancer antigen repertoire, including the reported and the unidentified antigens, but its immunogenicity is far from satisfactory. Cellular engineering approaches offer chances to endogenously modulate the immune-associated functions of cell membranes. Such a reinforced vaccine based on the engineered cancer cell membranes matches better the natural immune recognition pathway than the conventional vaccines. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF- α , IFN- γ , and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer. Cancer cell membrane-coated liposomal-paclitaxel-loaded bacterial ghosts (LP@BG@CCM) were prepared for the treatment of metastatic lung cancer by immune stimulation and lung targeting. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Hypothesis: The use of tumor cell membrane-camouflaged nanoparticles, specifically the multifunctional biomimetic core–shell nanosystem MPCONPs, can enhance the targeting ability and immune escape functionality of traditional chemotherapy, leading to more precise drug delivery and improved treatment outcomes. Experiments: Preparation of MPCONPs: Autologous tumor cell membrane (CM) fragments are collected and used to create a shell for the nanoparticles. A trypsin-sensitive cationic polylysine framework is synthesized and embedded with oxaliplatin (l -OHP) and Ce6-AuNDs (a singlet oxygen generator). The MPCONPs are formed by assembling these components. Findings: MPCONPs, as nanoparticles camouflaged with tumor CM, have enhanced cellular uptake in cancer cells and improved the efficacy of photodynamic therapy (PDT) and chemotherapy (CT). This offers great potential for their use as individualized therapeutic agents for clinical oncology treatment. [ABSTRACT FROM AUTHOR]

Jingmei Li,1,* Jin Zhang,1,* Yan Gao,1 Sibei Lei,1 Jieping Wu,1 Xiaohua Chen,1 Kaiyu Wang,1 Xingmei Duan,2 Ke Men1 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comIntroduction: Cell-membrane nanocarriers are usually constructed by modifying the nanoparticle surface with cell membrane extracts, which has a direct benefit in endowing targeting capacity to nanocarriers based on their original cell types. However, delivering nucleic acid cargos by cell membrane–based nanoparticles is difficult owing to the strong negative charge of the cell membrane fraction. In this study, we developed a cancer cell membrane–based drug delivery system, the cMDS, for efficient siRNA delivery. Meanwhile, the cancer-specific immune response stimulated by the gene vector itself could offer synergistic anti-cancer ability.Methods: The cMDS was prepared by ultrasound, and its transfection efficiency and anti-cancer ability were examined using cultures of CT26 cells. MTT and red blood cell hemolysis tests were performed to assess the safety of cMDS, while its targeted gene delivery and strong immune stimulation were investigated in a subcutaneous tumor model. Moreover, the detailed anti-cancer immune stimulation mechanisms of cMDS are uncovered by protein chip analysis.Results: The cMDS was spherical core-shell structure. It showed high transfection efficiency and anti-cancer ability in vitro. In animal experiments, intravenously administered cMDS/siStat3 complex efficiently suppress the growth of colon cancer. Moreover, the result of protein chip analysis suggested that cMDS affect the migration and chemotaxis of immune cells.Conclusion: The cMDS shows obvious tumor tissue-specific accumulation properties and strong immune stimulation ability. It is an advanced targeted gene delivery system with potent immunotherapeutic properties.Keywords: bioinspired material, cancer cell membrane, targeted siRNA delivery, immunotherapeutic, colon cancer

Abstract Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. Graphical Abstract

Purpose: This study aims at chemotherapy and starvation therapy of HCC via starvation and apoptosis. Methods: Hollow mesoporous organosilica nanoparticles (HMONs) with the thioether-hybrid structure were developed using an organic/inorganic co-templating assembly approach. Hydrofluoric acid was used to remove the internal MSN core for yielding large radial mesopores for loading drug cargos. The morphology and structure of NPs were determined using TEM and SEM. HMONs were stepwise surface modified with glucose oxidase (GOx), oxygen (O2) and Doxorubicin (DOX), and cancer cell membrane (CCM) for yielding CCM-coated HMONs (targeted stealth biorobots; TSBRs) for starvation, apoptotic, and enhanced cell uptake properties, respectively. The surface area and pore size distribution were determined via BET and BJH assays. The catalytic ability of GOx-modified NPs was measured using in vitro glucose conversion approach authenticated by H2O2 and pH determination assays. MTT assay was used to determine the cytotoxicities of NPs. Cell uptake and apoptotic assay were used for the NPs internalization and apoptosis mechanisms. The subcutaneous HepG2 tumor model was established in mice. The long-term in vivo toxicity was determined using blood assays. Results: The prepared NPs were spherical, hollow and mesoporous with excellent surface area and pore size distribution. The GOx-modified NPs exhibited excellent catalytic activity. The TSBRs showed better cytotoxicity and reduce the tumor size and weight. The NPs showed long-term safety in vivo. Conclusion: TSBRs destroyed cancer cells by starvation and chemotherapy in both in-vitro and in-vivo settings which demonstrates its anti-cancer potential. [ABSTRACT FROM AUTHOR]

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. [ABSTRACT FROM AUTHOR]

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor. [ABSTRACT FROM AUTHOR]

Background: Selective cancer cell recognition is the most challenging objective in the targeted delivery of anti-cancer agents. Extruded specific cancer cell membrane coated nanoparticles, exploiting the potential of homotypic binding along with certain protein-receptor interactions, have recently proven to be the method of choice for targeted delivery of anti-cancer drugs. Prediction of the selective targeting efficiency of the cancer cell membrane encapsulated nanoparticles (CCMEN) is the most critical aspect in selecting this strategy as a method of delivery. Materials and methods: A probabilistic model based on binding scores and differential expression levels of Glioblastoma cancer cells (GCC) membrane proteins (factors and receptors) was implemented on python 3.9.1. Conditional binding efficiency (CBE) was derived for each combination of protein involved in the interactions. Selective propensities and Odds ratios in favour of cancer cells interactions were determined for all the possible combination of surface proteins for 'k' degree of interaction. The model was experimentally validated by two types of Test cultures. Results: Several Glioblastoma cell surface antigens were identified from literature and databases. Those were screened based on the relevance, availability of expression levels and crystal structure in public databases. High priority eleven surface antigens were selected for probabilistic modelling. A new term, Breakeven point (BEP) was defined as a characteristic of the typical cancer cell membrane encapsulated delivery agents. The model predictions lie within ±7% of the experimentally observed values for both experimental test culture types. Conclusion: The implemented probabilistic model efficiently predicted the directional preference of the exposed nanoparticle coated with cancer cell membrane (in this case GCC membrane). This model, however, is developed and validated for glioblastoma, can be easily tailored for any type of cancer involving CCMEN as delivery agents for potential cancer immunotherapy. This probabilistic model would help in the development of future cancer immunotherapeutic with greater specificity. [ABSTRACT FROM AUTHOR]

Abstract Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with poor prognosis. Although anatomical imaging figures prominently for breast lesion screening, TNBC is often misdiagnosed, thus hindering early medical care. Ultrasound (US) molecular imaging using nanobubbles (NBs) capable of targeting tumor cells holds great promise for improved diagnosis and therapy. However, the lack of conventional biomarkers in TNBC impairs the development of current targeted agents. Here, we exploited the homotypic recognition of cancer cells to synthesize the first NBs based on TNBC cancer cell membrane (i.e., NBCCM) as a targeted diagnostic agent. We developed a microfluidic technology to synthesize NBCCM based on the self-assembly property of cell membranes in aqueous solutions. In vitro, optimal NBCCM had a hydrodynamic diameter of 683 ± 162 nm, showed long-lasting US contrast enhancements and homotypic affinity. In vivo, we demonstrated that NBCCM showed increased extravasation and retention in a TNBC mouse model compared to non-targeted NBs by US molecular imaging. Peak intensities and areas under the curves from time-intensity plots showed a significantly enhanced signal from NBCCM compared to non-targeted NBs (2.1-fold, P = 0.004, and, 3.6-fold, P = 0.0009, respectively). Immunofluorescence analysis further validated the presence of NBCCM in the tumor microenvironment. Circumventing the challenge for universal cancer biomarker identification, our approach could enable TNBC targeting regardless of tumor tissue heterogeneity, thus improving diagnosis and potentially gene/drug targeted delivery. Ultimately, our approach could be used to image many cancer types using biomimetic NBs prepared from their respective cancer cell membranes.

The application of paclitaxel (PTX) for chemotherapy of tongue squamous cell carcinoma shows unavoidable damage to normal tissue, thus need to develop drug delivery and tumor-targeting nanomaterials. Mesoporous silica nanoparticles (MSNs) exhibit advantages including a convenient synthesis process, adjustable structure, high drug loading efficiency and low cytotoxicity. In this study, we synthesized PTX-loaded calcium carbonate-coated degradable disulfide-doped MSNs to construct a pH/redox dual-responsive controlled-release nanosystem. A high PTX loading rate of 9.68 ± 0.21% was measured with significantly accelerated release at low pH and in the presence of GSH. Moreover, surface decoration of the cell membrane was conducted to realize homologous targeted killing of tongue squamous cell carcinoma cells (PTX/ssMSN@CaCO3@TC), as confirmed by dynamic light scattering and gel electrophoresis analyses. Our nanocomposite material could be effectively taken up by Tca8113 cells but not by L929 and HeLa cells. Moreover, excellent tumor killing performance was measured both in vitro and in vivo. A total of 94.00 ± 1.66% and 98.12 ± 0.28% of Tca8113 cells were killed after culturing for 1 day and 3 days, respectively. This study developed a novel nanomaterial with the abilities of homologous targeting and dual-responsive release of PTX in tumor cells, exhibiting great value for the design of nanotargeting tumor killing drugs.

BackgroundSelective cancer cell recognition is the most challenging objective in the targeted delivery of anti-cancer agents. Extruded specific cancer cell membrane coated nanoparticles, exploiting the potential of homotypic binding along with certain protein-receptor interactions, have recently proven to be the method of choice for targeted delivery of anti-cancer drugs. Prediction of the selective targeting efficiency of the cancer cell membrane encapsulated nanoparticles (CCMEN) is the most critical aspect in selecting this strategy as a method of delivery.Materials and methodsA probabilistic model based on binding scores and differential expression levels of Glioblastoma cancer cells (GCC) membrane proteins (factors and receptors) was implemented on python 3.9.1. Conditional binding efficiency (CBE) was derived for each combination of protein involved in the interactions. Selective propensities and Odds ratios in favour of cancer cells interactions were determined for all the possible combination of surface proteins for ‘k’ degree of interaction. The model was experimentally validated by two types of Test cultures.ResultsSeveral Glioblastoma cell surface antigens were identified from literature and databases. Those were screened based on the relevance, availability of expression levels and crystal structure in public databases. High priority eleven surface antigens were selected for probabilistic modelling. A new term, Break-even point (BEP) was defined as a characteristic of the typical cancer cell membrane encapsulated delivery agents. The model predictions lie within ±7% of the experimentally observed values for both experimental test culture types.ConclusionThe implemented probabilistic model efficiently predicted the directional preference of the exposed nanoparticle coated with cancer cell membrane (in this case GCC membrane). This model, however, is developed and validated for glioblastoma, can be easily tailored for any type of cancer involving CCMEN as delivery agents for potential cancer immunotherapy. This probabilistic model would help in the development of future cancer immunotherapeutic with greater specificity.

Abstract Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal–organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).

Abstract Background Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression. Results We describe a synergistic triple protocol combining photothermal and sonodynamic therapy (PTT and SDT), together with immune checkpoint blockade for the inhibition of breast cancer growth and metastases in the 4T1 mouse model. PTT and SDT are synergistically augmented by a novel multimodal imaging nanoprobe integrated with cancer cell membrane-biomimetic nanoparticles (CHINPs) loaded with superparamagnetic iron oxide (SPIO) and hematoporphyrin monomethyl ether (HMME). CHINPs exhibit excellent homologous tumor targeting, and are sequentially triggered by ultrasound and near infrared (NIR) light under the guidance of magnetic resonance, photoacoustic and photothermal imaging, leading to complete in situ tumor eradication and systemic anti-tumor immune activation. Further combination of this approach with immune checkpoint blockade therapy is shown to suppress tumor metastasis. Conclusion This work provides proof-of-principle for triple therapy using multimodal imaging-guided PTT/SDT based on biomimetic nanoprobes in combination with immunotherapy to eliminate tumors. Graphical Abstract

Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

Targeted therapy has the potential to revolutionize medical approaches to bring us closer to an effective personalized therapy model. In this work, we developed homologous-targeted magnetic nanowires coated with biologics-loaded zeolitic imidazolate frameworks and cellular membranes (ZNWs) to provide an increased therapeutic potential both in vitro and in vivo. In vitro, the uncoated ZNWs combined with laser treatment reduced cancer cell viability by 34.6%, whereas the coated ZNWs combined with laser treatment reduced cancer cell viability by 45.91%. In vivo, ZNWs accumulated selectively in MCF-7 cancer cells and maintained a high intensity for up to 120 h, which reduced tumor growth significantly. Combining gene and tumor ablation treatment with the homologous targeting ability of ZNWs resulted in about 73% cell death. We believe that using such an assembled coating to camouflage delivery vehicles has effective outcomes in terms of improved targeting and therapeutic efficiency and should be studied further for medical translation. [ABSTRACT FROM AUTHOR]

Hepatic carcinoma (HC) is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide. Sepantronium bromide (YM155) is a small molecule inhibitor of survivin, which has broad-spectrum anticancer therapeutic effects in various xenograft models. However, several-day continuous infusion is required to achieve greater antitumor efficacy because of rapid elimination from the blood circulation. Herein, a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system (DDS) (named as iM7721@GQD-YM), was developed for co-encapsulation of YM155 and graphene quantum dots (GQDs). Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells, excellent biocompatibility and favorable immunocompatibility for in vivo application. Surface decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin recognition. In addition, under the irradiation of near-infrared ray (NIR), GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture, accurately releasing YM155 at tumor sites. The physicochemical properties, in vivo and ex vivo anti-tumor efficacy, and mechanisms of iM7721@GQD-YM nanoparticles (NPs) were systematically investigated in this work. The experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC, which merits further investigation in both pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor, with a poor prognosis. Temozolomide (TMZ) represents the standard chemotherapy for GBM but has limited efficacy due to poor targeting and a hypoxic tumor microenvironment (TME). To address these challenges, we developed a dual-gas-releasing, cancer-cell-membrane-camouflaged nanoparticle to deliver TMZ. This nanoceria, camouflaged with a cancer cell membrane (CCM-CeO 2 ), targets explicitly GBM cells and accumulates in lysosomes, triggering the rapid release of TMZ. Additionally, CCM-CeO 2 could release oxygen (O 2 ) and nitric oxide (NO) in response to the TME. Synthesized using d-arginine, catalytic nanoceria could decompose excessive hydrogen peroxide (H 2 O 2 ) in the TME to produce O 2 , while d-arginine could nonenzymatically react with H 2 O 2 to generate NO. CCM-CeO 2 could penetrate GBM spheroids to a depth of 148.3 ± 31 μm, with the O 2 and NO produced, reducing HIF-1α protein expression. When loaded with TMZ, CCM-CeO 2 could increase the intracellular ROS produced by TMZ, leading to lysosome membrane permeabilization and notably augmented apoptosis and necrosis in GBM cells. An in vitro antitumor assay using spheroids showed that CCM-CeO 2 reduced the IC 50 value of TMZ from 174.5 to 42.6 μg/mL, likely due to the catalase-like activity of nanoceria. These results suggest that alleviating hypoxia and increasing ROS produced by chemotherapeutics could be an effective therapeutic strategy for treating GBM.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 μM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo . Moreover, the MICFNS with 40/10 μM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

Glioblastoma multiforme (GBM), the most aggressive intracranial neoplasm, remains incurable at present, primarily due to drug resistance, which significantly contributes to elevated recurrence rates and dismal prognosis. Signal transducer and activator of transcription 3 (STAT3) is a critical gene closely associated with GBM drug resistance and the progression of GBM stem cells (GSCs), making it a promising therapeutic target. In this study, we developed cancer cell membrane-cloaked biomimetic nanoparticles to deliver STAT3 siRNA to reverse drug resistance in homologous GBM. These biomimetic nanoparticles leverage homotypic targeting, rapid endosome escape, and fast siRNA release, leading to efficient in vitro STAT3 knockdown in both temozolomide-resistant U251-TR cells and X01 GSCs. Moreover, benefited from the membrane functionalization, significant prolonged blood circulation, improved blood brain barrier (BBB) penetration and GBM tumor accumulation are achieved by these siRNA biomimetic nanoparticles. Importantly, these nanoparticles effectively inhibit tumor proliferation, significantly extending median survival time in orthotopic U251-TR (43.5 d versus 20 d for PBS control) and X01 GSC-bearing mouse xenografts (52 d versus 19.5 d for PBS control). Altogether, this biomimetic siRNA platform offers a promising strategy for gene therapy targeting drug-resistant GBM., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1 O 2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1 O 2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy., (© 2024 Wiley‐VCH GmbH.)

[Display omitted] To explore the immune adjuvant effect of nano mesoporous materials and laser immune effect of cancer therapy combined with chemotherapy, we designed a bionic nano tumor targeting delivery system with homologous cancer cell membrane as the outermost layer. Inorganic mesoporous silica (mSiO 2) and hydroxyapatite (HAP) are used as the intermediate immune adjuvant layer and drug carrier layer, and gold nanorods(GNR) are used as the core. It degrade to release drug under the condition of low pH value, and the gold nanorods are wrapped for near-infrared laser response. Homologous cancer cell membrane wrapping is expected to greatly improve the efficiency of targeted delivery. Laser immunotherapy is more widely applied than antibody and vaccine, and has no serious side effects. Combined with controlled release drug targeted chemotherapy and encapsulated with tumor cell membrane, it is expected to further achieve low toxicity and high efficiency cancer treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with poor prognosis. Although anatomical imaging figures prominently for breast lesion screening, TNBC is often misdiagnosed, thus hindering early medical care. Ultrasound (US) molecular imaging using nanobubbles (NBs) capable of targeting tumor cells holds great promise for improved diagnosis and therapy. However, the lack of conventional biomarkers in TNBC impairs the development of current targeted agents. Here, we exploited the homotypic recognition of cancer cells to synthesize the first NBs based on TNBC cancer cell membrane (i.e., NBCCM) as a targeted diagnostic agent. We developed a microfluidic technology to synthesize NBCCM based on the self-assembly property of cell membranes in aqueous solutions. In vitro, optimal NBCCM had a hydrodynamic diameter of 683 ± 162 nm, showed long-lasting US contrast enhancements and homotypic affinity. In vivo, we demonstrated that NBCCM showed increased extravasation and retention in a TNBC mouse model compared to non-targeted NBs by US molecular imaging. Peak intensities and areas under the curves from time-intensity plots showed a significantly enhanced signal from NBCCM compared to non-targeted NBs (2.1-fold, P = 0.004, and, 3.6-fold, P = 0.0009, respectively). Immunofluorescence analysis further validated the presence of NBCCM in the tumor microenvironment. Circumventing the challenge for universal cancer biomarker identification, our approach could enable TNBC targeting regardless of tumor tissue heterogeneity, thus improving diagnosis and potentially gene/drug targeted delivery. Ultimately, our approach could be used to image many cancer types using biomimetic NBs prepared from their respective cancer cell membranes. [ABSTRACT FROM AUTHOR]

BackgroundAs the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy.Key scientific concepts of reviewCCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology.ConclusionThis review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.

Peiqi Zhao, Lihua Qiu, Shiyong Zhou, Lanfang Li, Zhengzi Qian, Huilai Zhang Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Huilai ZhangDepartment of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, 24 Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of ChinaTel +86-22-23340123Email zhlwgq@126.comPurpose: Although anti-programmed cell death protein 1 antibody (aPD1) immunotherapy and chemotherapy has made much progress in the treatment of melanoma, the efficacy still needs to be further improved.Methods: Cancer treatment has been greatly enhanced by the use of nanotechnology. Cancer cell membrane (CCM)-camouflaged nanoparticles have shown promising potential in tumor therapy due to their excellent homologous-targeting ability, long blood circulation and immune escape. This work presents a biocompatible and tumor acidic environmental responsive CCM-camouflaged mesoporous silica nanoparticle (CMSN) that is loaded with dacarbazine (DTIC) and combined with aPD1 to achieve better antitumor efficacy.Results: In vitro cell experiments demonstrated that DTIC@CMSN exhibits a better anti-tumor killing efficiency and a stronger ability to promote the apoptosis of tumor cells than free DTIC. In vivo antitumor results demonstrated that combination therapy of DTIC@CMSN chemotherapy and aPD1 immunotherapy remarkably suppress the melanoma growth and prolong survival time due to highly selective tumor killing, activation of tumor-specific T cells, and regulation of the immunosuppressive tumor microenvironment. In addition, safety evaluation studies of DTIC@CMSN also demonstrate their increased tumor accumulation and decreased systemic toxicity.Conclusion: This study provides a promising nano-platform for the combination of chemotherapy with immunotherapy, which is potentially useful for the treatment of melanoma.Keywords: anti-PD-1, cancer cell membrane, cancer immunotherapy, melanoma, mesoporous silica nanoparticle

Shini Feng,1 Yajing Ren,1 Hui Li,1 Yunfei Tang,1 Jinyu Yan,1 Zeyuan Shen,1 Huijie Zhang,2 Fuxue Chen1 1School of Life Sciences, Shanghai University, Shanghai, 200444, People’s Republic of China; 2School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, People’s Republic of ChinaCorrespondence: Fuxue ChenSchool of Life Sciences, Shanghai University, Shanghai, 200444, People’s Republic of ChinaTel/Fax +86-21-6613-5167Email chenfuxue@staff.shu.edu.cnPurpose: Nanomaterial-based drug-delivery systems allowing for effective targeted delivery of smallmolecule chemodrugs to tumors have revolutionized cancer therapy. Recently, as novel nanomaterials with outstanding physicochemical properties, boron nitride nanospheres (BNs) have emerged as a promising candidate for drug delivery. However, poor dispersity and lack of tumor targeting severely limit further applications. In this study, cancer cell–membrane biomimetic BNs were designed for targeted anticancer drug delivery.Methods: Cell membrane extracted from HeLa cells (HM) was used to encapsulate BNs by physical extrusion. Doxorubicin (Dox) was loaded onto HM-BNs as a model drug.Results: The cell-membrane coating endowed the BNs with excellent dispersibility and cytocompatibility. The drug-release profile showed that the Dox@HM-BNs responded to acid pH, resulting in rapid Dox release. Enhanced cellular uptake of Dox@HM-BNs by HeLa cells was revealed because of the homologous targeting of cancer-cell membranes. CCK8 and live/dead assays showed that Dox@HM-BNs had stronger cytotoxicity against HeLa cells, due to self-selective cellular uptake. Finally, antitumor investigation using the HeLa tumor model demonstrated that Dox@HM-BNs possessed much more efficient tumor inhibition than free Dox or Dox@BNs.Conclusion: These findings indicate that the newly developed HM-BNs are promising as an efficient tumor-selective drug-delivery vehicle for tumor therapy.Keywords: boron nitride nanospheres, cancer-cell membrane, targeted drug delivery, chemotherapy, biomimetic

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment. [Display omitted] • Paclitaxel nanoparticles coated with A549 cell membranes (AM@PTX-NPs) were developed. • AM@PTX-NPs showed a high drug loading efficiency and steady drug release property. • A549 cell membrane coating enhanced the tumor targeting ability of PTX nanoparticles. • AM@PTX-NPs displayed significantly higher antitumor effects in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery. [Display omitted] • An active and homologous dual targeting RGD-CCM-LP-DOX was prepared for enhanced tumor targeting. • RGD-CCM-LP-DOX exhibited superior tumor cell affinity and cellular uptake efficiency. • RGD-CCM-LP-DOX improved the accumulation of DOX in tumor sites of tumor-bearing mice. • RGD-CCM-LP-DOX showed improved anti-tumor efficiency and reduced side effects. [ABSTRACT FROM AUTHOR]

Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.

Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal–organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity. [ABSTRACT FROM AUTHOR]

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA- co -HP- β -cyclodextrin- co -Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ , followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days). A cancer cell membrane-coated pH-responsive nanogel to co-deliver paclitaxel (PTX) and immunotherapeutic agent IL-2, for combinational treatment of triple-negative breast cancer was reported here. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Non-Hodgkin’s lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. Results Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. Conclusions Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.

Background: Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression. Results: We describe a synergistic triple protocol combining photothermal and sonodynamic therapy (PTT and SDT), together with immune checkpoint blockade for the inhibition of breast cancer growth and metastases in the 4T1 mouse model. PTT and SDT are synergistically augmented by a novel multimodal imaging nanoprobe integrated with cancer cell membrane-biomimetic nanoparticles (CHINPs) loaded with superparamagnetic iron oxide (SPIO) and hematoporphyrin monomethyl ether (HMME). CHINPs exhibit excellent homologous tumor targeting, and are sequentially triggered by ultrasound and near infrared (NIR) light under the guidance of magnetic resonance, photoacoustic and photothermal imaging, leading to complete in situ tumor eradication and systemic anti-tumor immune activation. Further combination of this approach with immune checkpoint blockade therapy is shown to suppress tumor metastasis. Conclusion: This work provides proof-of-principle for triple therapy using multimodal imaging-guided PTT/SDT based on biomimetic nanoprobes in combination with immunotherapy to eliminate tumors. [ABSTRACT FROM AUTHOR]

[Display omitted] In view of the photothermal effect of polydopamine (PDA) nanoparticles and their internal D-π-D structures during assembly, the two-photon excited properties of PDA were studied toward the biomedical application. Further, the PDA molecules were coordinated with Mn2+ and the assembled nanoparticles were covered by cancer cell membranes, the complex system could be used directly for the treatment of cancer with photothermal and chemodynamic therapy. The two-photon excited PDA-Mn2+ nanoparticles were used for the photothermal therapy combined with chemodynamic therapy. The complexes were coated with cancer cell membranes in order to enhance the tumor homologous efficiency. Multi-modal bioimaging and anti-tumor detections were carried out both in vitro and in vivo. PDA nanoparticles were demonstrated to have both good two-photon excited fluorescence and photothermal efficiency. The assembled nanoparticles modified with Mn2+ and cancer cell membranes have an obvious targeting and synergetic anti-cancer efficiency. The system creates a simple way for a precise operation with multi-modal imaging function. [ABSTRACT FROM AUTHOR]

Nanoparticles coated with cell membranes have been garnering growing attention due to their homologous binding capability of membrane molecules and consequent self-recognition by their source cells. In the present study, we report on the construction of doxorubicin and PD-L1 siRNA-loaded PLGA nanoparticles and their biological functionalization by cancer cell-derived membrane cloaking. The resulting cancer cell membrane-coated nanoparticles (CCMNPs) presented a core-shell nanostructure with highly specific self-recognition affinity to the homotypic cells, which can be attributed to the transference of cell adhesion molecules with homotypic binding properties. These findings facilitate the application of this bioinspired strategy for effective delivery of siRNA and precise tumour therapy.

To fulfill the demand of precision and personalized medicine, single‐atom catalysts (SACs) have emerged as a frontier in biomedical fields due to enzyme‐mimic catalysis. Herein, we present a biocompatible and versatile nanoagent consisting of single‐atom iron‐containing nanoparticles (SAF NPs), DOX and A549 cell membrane (CM). The designed porous iron‐based SACs originally served as a drug‐carrying nanoplatform to release DOX selectively in a tumor microenvironment (TME) for chemotherapy (CT) due to their high loading capacity (155 %) for DOX; this signifies that SACs are promising candidates for universal cargo delivery. Besides, the designed single‐atom nanoagent can perform like peroxidase, which effectively triggers an in situ tumor‐specific Fenton reaction to generate abundant toxic hydroxyl radicals (⋅OH) selectively in the acidic TME for chemodynamic therapy (CDT). With the combination of CDT and CT, the constructed SAF NPs@DOX@CM nanoagent demonstrates better in vivo therapeutic performance than single‐pathway therapy. In the meantime, after modification with CM, SAF NPs@DOX@CM can achieve homologous binding to target tumor tissues and avoid early clearance. This study presents a type of multifunctional SACs for enhanced cancer treatment via the capacity of a drug carrier combined with the enzymatic therapies of single‐atom catalytic sites. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has been reported to be the third common malignant tumor because of the high rate of mortality. Photosensitizers (PSs) based on the natural products have been widely used in clinical antitumor research contributed to their excellent biological activity. To increase the PSs' safety and efficacy of HCC, the tumor cell membrane coating drug nanocrystals featured with homologous immune escape and targeting ability and low toxicity are in high demand. In this study, we reported a targeting drug delivery system based on a modified cell membrane coating technique and drug nanocrystals. HepG2 cell membrane was modified with targeting receptor through a biochemical reaction including Maleimide reaction. Modified with the HepG2-targeting protein transferrin, the resulting TF-CCCM-HB NPs exhibited long-term stability, excellent biocompatibility, high drug loading, and low toxicity. Compared with HB NPs, TF-CCCM-HB NPs showed both excellent targeting and therapeutic efficacy in BALB/c nude mouse bearing with HepG2 tumors. Therefore, TF-CCCM, a biomimetic drug delivery platform, can be readily generalized to the delivery of various drugs and provide a sound strategy for the treatment of other cancers via changes in the corresponding homotypic cancer cell membrane.

Bi nanoparticles have been camouflaged with CT26 cancer cell membrane, and then they exhibit long circulation time and good homotypic-targeting capabilities, resulting in effective photothermal therapy of tumors. [Display omitted] • The successful camouflage of Bi NPs with CT26 CCM. • Longer blood circulation and more efficient tumor accumulation of Bi@CCM NPs. • Efficient photothermal ablation of tumors. Bi nanoparticles (NPs) have been demonstrated as effective all-in-one type theranostic agent for imaging-guided photothermal therapy, but their applications have been limited by relatively low biocompatibility and target accumulation capacity. To address this issue, we report the camouflage of Bi NPs (size: ~42 ± 2 nm) by using the mouse colon cancer CT26 cells membrane (CT26 CCM). The camouflaging process confers the efficient coating of CCM shell layer with thickness of ~8 ± 2 nm on Bi NPs cores, which can be confirmed by TEM image, zeta potential and protein gel electrophoresis tests. Simultaneously, CCM shell has no side effects on the photoabsorption/photothermal effect. Importantly, Bi@CCM NPs retain significant features of CCM, including good biocompatibility and homologous targeting ability. When Bi@CCM dispersion was intravenously (i.v.) injected into mice, they exhibited higher blood circulation half-life (11.5 h, ~2.9 times) and accumulation amount (4.7 ± 0.56% ID/g, ~2.3 times) in homotypic CT26 tumor compared to those (4.0 h in blood and 2.03 ± 0.60% ID/g in tumor) from uncoated Bi NPs. After 808 nm laser irradiation, CT26 cancer cells could be effectively ablated after the photothermal therapy of high-accumulated Bi@CCM NPs, and then the tumor tends to be eradicated after 12 days. Thus, Bi NPs camouflaged with CT26 CCM have great potential for the targeted photothermal therapy of homotypic tumors. [ABSTRACT FROM AUTHOR]

The development of an effective delivery system for peptides targeting the tumor microenvironment has always been a hot topic of research in the field of cancer diagnosis and therapy. In this study, superparamagnetic iron oxide nanoparticles (SPIO NPs) were encapsulated with H460 lung cancer cell membranes (SPIO NP@M), and two peptides, namely PD-L1 inhibitory peptide (TPP1) and MMP2 substrate peptide (PLGLLG), were conjugated to the H460 membrane (SPIO NP@M-P). Homologous targeting, cytotoxicity, and pharmacokinetics of SPIO NP@M-P were evaluated. The TPP1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor-specific enzyme MMP2. The newly developed delivery system (SPIO NP@M-P) for the PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer than that for peptides alone) and could maintain the ability to reactivate T cells and inhibit the tumor growth both in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus show the effect of peptide treatment. The SPIO NP@M might serve as a promising theranostic platform for therapeutic application of peptides in cancer therapy. A multifunctional delivery system (SPIO NP@M) was constructed for effectively delivering therapeutic peptides into the tumor microenvironment for cancer diagnosis and therapy. In this paper, the TPP-1 peptide inhibiting the binding of PD-L1 and PD-1 was delivered and released into the tumor microenvironment by the homotypic targeting of H460 cell membrane and specific digestion by the MMP2 enzyme. SPIO NPs in this system were aggregated effectively at the tumor sites and were used for magnetic resonance imaging of tumors. The SPIO NP@M-P delivery system could effectively extend the half-life of the TPP-1 peptide (60 times longer than that of the free peptide) and could maintain the ability to re-activate T cells and inhibit tumor growth in vitro and in vivo. In conclusion, the SPIO NP@M system coated with lung cancer cell membrane and loaded with the PD-L1-blocking TPP-1 peptide could be a promising integrated platform for tumor diagnosis and treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Current cancer therapy usually succumbs to many extracellular and intracellular barriers, among which untargeted distribution and multidrug resistance (MDR) are two important difficulties responsible for poor outcome of many drug delivery systems (DDS). Here, in our study, the dilemma was addressed by developing a cancer cell membrane (CCM)-coated silica (SLI) nanoparticles to co-deliver miR495 with doxorubicin (DOX) for effective therapy of lung cancer (CCM/SLI/R-D). The homologous CCM from MDR lung cancer cells (A549/DOX) was supposed to increase the tumor-homing property of the DDS to bypass the extracellular barriers. Moreover, the MDR of cancer cells were conquered through downregulation of P-glycoprotein (P-gp) expression using miR495. It was proved that miR495 could significantly decrease the expression of P-gp which elevated intracellular drug accumulation in A549/DOX. The in vitro and in vivo results exhibited that CCM/SLI/R-D showed a greatly enhanced therapeutic effect on A549/DOX, which was superior than applying miR495 or DOX alone. The preferable effect of CCM/SLI/R-D on conquering the MDR in lung cancer provides a novel alternative for effective chemotherapy of MDR cancers.

Background: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. Results: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. Conclusions: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma. [ABSTRACT FROM AUTHOR]

In Chinese traditional medicine, quercetin (QT) plays a fundamental role in the treatment of asthma, as an anti-allergen and to lower blood pressure. Recent evidence suggests that QT can improve tumor radiosensitivity through multiple mechanisms. However, poor tumor tissue targeting ability and low water solubility of QT limit its usefulness in the treatment of cancers. Herein, we designed a novel drug delivery system (CQM) consisting of inner QT loaded mesoporous silica nanoparticles (MSNs) and outer cancer cell membranes (CM). The developed nanoplatform had strong anti-cancer effects under X-ray irradiation and good QT loading characteristics. In addition, CQM effectively targeted tumor tissues. Results of in vitro and in vivo experiments demonstrated that the developed CQM drug delivery system has excellent tumor targeting ability and effectively inhibited tumor growth. Therefore, the CQM platform realized targeted drug delivery and radiotherapy sensitization, which provided a newfangled idea of cancer treatment.

In addition to being biological barriers where the internalization or release of biomolecules is decided, cell membranes are contact structures between the interior and exterior of the cell. Here, the processes of cell signaling mediated by receptors, ions, hormones, cytokines, enzymes, growth factors, extracellular matrix (ECM), and vesicles begin. They triggering several responses from the cell membrane that include rearranging its components according to the immediate needs of the cell, for example, in the membrane of platelets, the formation of filopodia and lamellipodia as a tissue repair response. In cancer, the cancer cells must adapt to the new tumor microenvironment (TME) and acquire capacities in the cell membrane to transform their shape, such as in the case of epithelial−mesenchymal transition (EMT) in the metastatic process. The cancer cells must also attract allies in this challenging process, such as platelets, fibroblasts associated with cancer (CAF), stromal cells, adipocytes, and the extracellular matrix itself, which limits tumor growth. The platelets are enucleated cells with fairly interesting growth factors, proangiogenic factors, cytokines, mRNA, and proteins, which support the development of a tumor microenvironment and support the metastatic process. This review will discuss the different actions that platelet membranes and cancer cell membranes carry out during their relationship in the tumor microenvironment and metastasis.