Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)‐camouflaged hollow MnO2 (HMnO2) catalytic nanosystem ...embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long‐circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2, which can be produced during the decomposition of endogenous H2O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti‐PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.
A strategy based on intra/extracellular lactic acid exhaustion is reported to achieve synergistic metabolic therapy and immunotherapy of tumors. This strategy is performed by a cascade catalytic nanosystem (PMLR) that integrates a hollow MnO2 nanocarrier with lactate oxidase and a glycolysis inhibitor.
Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in ...mammals, an aggressive man‐made RBC (AmmRBC) is created to combat the hypoxia‐mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme‐mimicking polydopamine, and polydopamine‐carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen‐carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man‐made pseudo‐RBC shows potentials as a universal oxygen‐self‐supplied platform to sensitize hypoxia‐limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.
Aggressive man‐made pseudo‐red blood cells (AmmRBCs) are prepared for self‐oxygen‐supplied photodynamic therapy (PDT) toward tumors. AmmRBCs can accumulate in tumors and exhibit high efficacy to combat hypoxia‐induced resistance of tumors to PDT, leading to complete tumor elimination.
Surface modification of nanomaterials is essential for their biomedical applications owing to their passive immune clearance and damage to reticuloendothelial systems. Recently, a cell ...membrane‐coating technology has been proposed as an ideal approach to modify nanomaterials owing to its facile functionalized process and good biocompatibility for improving performances of synthetic nanomaterials. Here, recent advances of cell membrane‐coated nanomaterials are reviewed based on the main biological functions of the cell membrane in living cells. An overview of the cell membrane is introduced to understand its functions and potential applications. Then, the applications of cell membrane‐coated nanomaterials based on the functions of the cell membrane are summarized, including physical barrier with selective permeability and cellular communication via information transmission and reception processes. Finally, perspectives of biomedical applications and challenges about cell membrane‐coated nanomaterials are discussed.
Recent advances of cell membrane‐coated nanomaterials are summarized here based on the main biological functions of the cell membrane, including physical barrier and cellular communication. Perspectives of biomedical applications and challenges of cell membrane‐coated nanomaterials are also discussed.
Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and ...traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co‐stimulatory molecules for robust immunotherapy. FMs share the tumor's self‐targeting character with the parent cancer cells. In bilateral tumor‐bearing mouse models, the FM‐coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post‐nanophotosensitizer‐induced photodynamic therapy (PDT). The FM‐induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy‐caused regression of the irradiation‐free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor‐specific immunotherapy‐based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.
Using the cytomembranes of fused cells derived from tumor and dendritic cells, a tumor‐specific immunotherapeutic platform is engineered, which is capable of easy cooperation with other therapy means. The hybrid‐cytomembrane‐coated nanophotosensitizer demonstrates durable immunotherapy against primary tumors post‐photodynamic‐therapy (PDT) and PDT‐enhanced immunity toward irradiation‐free distant tumors.
Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and ...advanced immunotherapy. Here, a multifunctional biomimetic core–shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH‐sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core–shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia‐inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD‐L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD‐1) antibody, the dual inhibition of the PD‐1/PD‐L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.
This work demonstrates a multifunctional biomimetic nanoplatform for reduced tumor chemoresistance and dual inhibition of programmed death 1/programmed death ligand 1 axis by the means of downregulating the expression of hypoxia‐inducible factor 1α, which elicits a significant immune response and presents a robust effect in lengthening tumor recurrence time and inhibiting tumor metastasis.
Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re‐educate immune cells to protect the host. However, the functions of NK cells are often limited in ...the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re‐education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H2O2). The generated H2O2 is also similar to cytokines and chemokines for recruiting immune cells and re‐educating survived macrophages to attack tumor cells. In addition, the oxygen‐carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.
Artificial natural killer (NK) cells are constructed with minor limitations of the immunosuppressive tumor microenvironment for specific tumor killing and renegade macrophage re‐education. The artificial NK cells exhibit efficient tumor inhibition and immune activation as a new sight to overcome tumors by simulating the functions of immune cells.
Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed ...cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.
The clinical application of antitumor immunotherapy still faces severe challenges related to efficacy. Here, a light‐triggered core–shell nanosystem is designed to boost antitumor immune response via ...controlled release of anti‐PD‐L1 (αPD‐L1) antibodies and enhanced antigen presentation. The nanosystem (AZ‐P@P) is constructed via integrating gold nanorods (AuNRs) as a photothermal core and zeolitic imidazolate framework‐8 (ZIF‐8) as a shell for aPD‐L1 delivery, and further PEGylating. In the nanosystem, the ZIF‐8 shell protects αPD‐L1 antibody from the complex physiological environment and hyperthermia. Once accumulated at the tumor site, AZ‐P@P under near‐infrared (NIR) light‐triggered heating induces tumor cell deaths releasing tumor‐derived protein antigens (TDPAs) and adenosine triphosphate (ATP). Thereafter, the released ATP degrades the ZIF‐8 shell to expose the AuNRs, which can promote intratumoral T cell infiltration by capturing TDPAs and transporting them to dendritic cells (DCs). Concurrently, a large amount of αPD‐L1 is released in situ to reinvigorate T cell activity. Mechanistic studies reveal that AZ‐P@P promotes the maturation of DCs and the infiltration of activated T cells, thus eliciting a robust antitumor immunity. It is demonstrated that AZ‐P@P triggered by NIR light can significantly destroy primary tumors and suppress metastasis. This multiple immunoregulatory system provides a promising tool for tumor treatment.
An integrated core–shell nanosystem is designed to achieve the near‐infrared light‐triggered immune response by controlling the release of αPD‐L1 antibodies and enhancing the release and presentation of antigens. After local photothermal treatment, this nanosystem can induce a robust antitumor immune response to effectively inhibit tumor metastasis.
Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor ...targeting nanoplatform, designated as Me&Flu@MSN@MnO
-FA, was fabricated for effective tumor suppression and anti-metastasis by interfering with lactate metabolism of tumor cells. Metformin (Me) and fluvastatin sodium (Flu) were incorporated into MnO
-coated mesoporous silicon nanoparticles (MSNs), the synergism between Me and Flu can modulate the pyruvate metabolic pathway to produce more lactate, and concurrently inhibit lactate efflux to induce intracellular acidosis to kill tumor cells. As a result of the restricted lactate efflux, the extracellular lactate concentration is reduced, and the ability of the tumor cells to migrate is also weakened. This ingenious strategy based on Me&Flu@MSN@MnO
-FA showed an obvious inhibitory effect on tumor growth and resistance to metastasis.
The short lifetime of singlet oxygen reduces its accumulation in the endoplasmic reticulum, which limits the output of photodynamic therapy. A nanodevice with functions of singlet oxygen production, ...storage and release can improve the lifetime of singlet oxygen for enhancing phototherapeutic efficacy.
A nanodevice was designed with functions of singlet oxygen production, storage and release to improve the lifetime of singlet oxygen for enhancing photodynamic therapy.
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