Recent breakthroughs in cell membrane-fabricated nanovaccine offer innovateive therapeutic options for preventing tumor metastasies and recurrence, yet the treatment of patient-specific solid tumor remained challenging owing to the immunosuppressive tumor microenvironment. Herein, we developed a personalized photothermal nanovaccine based on the surgical tumor-derived cell membranes (CMs) coating resiquimod (R848) loaded mesoporous polydopamine (MPDA) nanoparticles for targeting tumor photothermal immunotherapy and prevention. The fabricated photothermal nanovaccine MPDA-R848@CM (MR@C) demonstrates outstanding imaging-guided photothermal immunotherapy efficacy to eradicate solid tumors under near-IR laser irradiation and further inhibiting metastasis tumors by the resulted antitumor immunities, especially in combination with programmed death-ligand 1 antibody therapy (aPD-L1). Furthermore, from in vivo prophylactic testing results, it is confirmed that the 4T1 cells rechallenge can be prevented 100% in postsurgical tumor model after vaccination of the photothermal nanovaccine. Our work fabricates a personalized photothermal nanovaccine that possesses great potential for tumor-specific treatment and for preventing postoperative tumor recurrence.

renal cell carcinoma (RCC), [2] and nonsmall cell lung carcinoma (NSCLC). [3] Through active or passive means, tumor immunotherapy induces the body to produce a tumor-specific immune response which suppresses the tumor progression and prevents the tumor recurrence or metastasis. [4][5][6] Strategies reported for tumor immunotherapy so far mainly involved immune checkpoint blockade (ICB), [7] adoptive cell transfer therapy (ACT), [8] tumor-specific vaccines, [9] and application of small molecular immunemodulating drugs. [10] However, most immunotherapy methods often encounter the great challenge of not being effective enough for many tumors of which a large amount do not respond in the clinic, [11,12] requiring advanced tumor immunotherapy methods to be developed.Among various tumor immunotherapy strategies, inhibition of the indoleamine-2,3-dioxygenase (IDO) is drawing great attention at present because of its critical role in mediating tumor immune evasion, and some inspiring studies were reported. [13][14][15] Admittedly, IDO catalyzes the degradation of amino acid l-tryptophan (Trp) into the metabolite l-kynurenine (Kyn), which suppresses cytotoxic T lymphocytes (CTL) and activates regulatory T (Treg) cells. [16,17] The strong immunomodulatory functions of IDO can be attributed Immunotherapy brings great benefits for tumor therapy in clinical treatments but encounters the severe challenge of low response rate mainly because of the immunosuppressive tumor microenvironment. Multifunctional nanoplatforms integrating effective drug delivery and medical imaging offer tremendous potential for cancer treatment, which may play a critical role in combinational immunotherapy to overcome the immunosuppressive microenvironment for efficient tumor therapy. Here, a nanodrug (BMS-SNAP-MOF) is prepared using glutathione (GSH)-sensitive metal-organic framework (MOF) to encapsulate an immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) inhibitor BMS-986205, and the nitric oxide (NO) donor s-nitrosothiol groups. The high T1 relaxivity allows magnetic resonance imaging to monitor nanodrug distribution in vivo. After the nanodrug accumulation in tumor tissue via the EPR effect and subsequent internalization into tumor cells, the enriched GSH therein triggers cascade reactions with MOF, which disassembles the nanodrug to rapidly release the IDO-inhibitory BMS-986205 and produces abundant NO. Consequently, the IDO inhibitor and NO synergistically modulate the immunosuppressive tumor microenvironment with increase CD8 + T cells and reduce Treg cells to result in highly effective immunotherapy.In an animal study, treatment using this theranostic nanodrug achieves obvious regressions of both primary and distant 4T1 tumors, highlighting its application potential in advanced tumor immunotherapy.

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A novel strategy of tumor microenvironment reprogramming by Intra/extracellular lactic acid exhausting for antitumor immune therapy.

Oxaliplatin (OXA) is a first-line chemotherapeutic agent for treating colorectal cancer (CC). However, the chemotherapeutic effect of OXA on CC is limited by the M2-like polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) and protective autophagy of tumor cells. Here, a cationic polymer APEG-PAsp(PEI) (PAPEI) was prepared to deliver smallinterfering RNA (siRNA) to silence the lactate dehydrogenase A (LDHA) gene (LDHA-siRNA) to enhance the chemotherapeutic effect of OXA on CC. The PAPEI/LDHA-siRNA nanocomplex effectively silenced the LDHA gene to inhibit the secretion of lactic acid from tumor cells, resulting in inhibition of the M2-like polarization of TAMs. In addition, the nanocomplex also amplified OXA-induced autophagy and transformed protective autophagy into autophagic death. Consequently, the combination treatment of OXA and PAPEI/LDHA-siRNA showed a dramatically increased chemotherapeutic effect on CC compared with the OXA-alone treatment, which also suggested its attractive potential for treating CC-like immune "cold" tumors.