Nanoparticle-based therapeutic, prevention, and detection modalities have the potential to greatly impact how diseases are diagnosed and managed in the clinic. With the wide range of nanomaterials available, the rational design of nanocarriers on an application-specific basis has become increasingly commonplace. Here, a comprehensive overview is provided on an emerging platform: cell-membrane-coating nanotechnology. As a fundamental unit of biology, cells carry out a wide range of functions, including the remarkable ability to interface and interact with their surrounding environment. Instead of attempting to replicate such functions via synthetic techniques, researchers are now directly leveraging naturally derived cell membranes as a means of bestowing nanoparticles with enhanced biointerfacing capabilities. This top-down technique is facile, highly generalizable, and has the potential to greatly augment existing nanocarriers. Further, the introduction of a natural membrane substrate onto nanoparticles surfaces has enabled additional applications beyond those traditionally associated with nanomedicine. Despite its relative youth, there exists an impressive body of literature on cell membrane coating, which is covered here in detail. Overall, there is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this developing technology.

Cell Membrane Coating Nanotechnology

Cancer immunotherapy is revolutionizing oncology. However, dose-limiting toxicities and low patient response rates remain major challenges in the clinic. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies in a safe and effective manner. In this Review, we discuss opportunities for combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. We highlight how nanoparticles can be used to reprogramme the immunosuppressive tumour microenvironment and to trigger systemic antitumour immunity, synergizing with immunotherapies against advanced cancer. Finally, we discuss strategies to improve tumour and immune cell targeting while minimizing toxicity and immune-related adverse events, and we explore the potential of theranostic nanoparticles for combination immunotherapy. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies. In this Review, the authors discuss combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy.

Cancer nanomedicine for combination cancer immunotherapy

Recent progress in drug delivery

An ideal cancer therapeutic strategy is expected to possess potent ability to not only ablate primary tumors but also prevent distance metastasis and relapse. In this study, human serum albumin was hybridized with hemoglobin by intermolecular disulfide bonds to develop a hybrid protein oxygen nanocarrier with chlorine e6 encapsulated (C@HPOC) for oxygen self-sufficient photodynamic therapy (PDT). C@HPOC realized the tumor-targeted co-delivery of photosensitizer and oxygen, which remarkably relieved tumor hypoxia. C@HPOC was favorable for more efficient PDT and enhanced infiltration of CD8+ T cells in tumors. Moreover, oxygen-boosted PDT of C@HPOC induced immunogenic cell death, with the release of danger-associated molecular patterns to activate dendritic cells, T lymphocytes, and natural killer cells in vivo. Notably, C@HPOC-mediated immunogenic PDT could destroy primary tumors and effectively suppress distant tumors and lung metastasis in a metastatic triple-negative breast cancer model by evoking syste...

Bioinspired Hybrid Protein Oxygen Nanocarrier Amplified Photodynamic Therapy for Eliciting Anti-tumor Immunity and Abscopal Effect

Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

Nanotechnology for Cancer Therapy Based on Chemotherapy.

A biomimetic nanogel with tumor microenvironment responsive property is developed for the combinatorial antitumor effects of chemotherapy and immunotherapy. Nanogels are formulated with hydroxypropyl-β-cyclodextrin acrylate and two opposite charged chitosan derivatives for entrapping anticancer drug paclitaxel and precisely controlling the pH responsive capability, respectively. The nanogel supported erythrocyte membrane can achieve “nanosponge” property for delivering immunotherapeutic agent interleukin-2 without reducing the bioactivity. By responsively releasing drugs in tumor microenvironment, the nanogels significantly enhanced antitumor activity with improved drug penetration, induction of calreticulin exposure, and increased antitumor immunity. The tumor microenvironment is remodeled by the combination of these drugs in low dosage, as evidenced by the promoted infiltration of immune effector cells and reduction of immunosuppressive factors.

Tumor Microenvironment Responsive Nanogel for the Combinatorial Antitumor Effect of Chemotherapy and Immunotherapy

A dual-sensitive nanoparticle delivery system was constructed by incorporating an acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ) and to realize the co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond, and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles. Consequently, the dual sensitive drug-loaded TSN delivery systems were successfully built and showed an obvious core-shell structure, good encapsulation efficiency of drugs, sustained and sensitive drug release, prolonged circulation time, as well as excellent synergistic antitumor efficiency against B16F10 tumor bearing mice. Moreover, the combinational antitumor immune responses of hydrazone bearing DOX/IFNγ-TSN (hyd) were strengthened by activating Th1-type CD4+ T cells, cytotoxic T lymphocytes, and natural killer cells, downregulating the expression levels of immunosuppressive cytokines, such as IL10 and TGFβ, and upregulating the secretion of IL2 and TNFα. Taken together, the multifunctional TSNs system provides a promising strategy for multiple drugs co-delivery with distinct properties.

Yijia Yin

Papers

Tumor Microenvironment Responsive Nanogel for the Combinatorial Antitumor Effect of Chemotherapy and Immunotherapy

Co-delivery of Doxorubicin and Interferon-γ by Thermosensitive Nanoparticles for Cancer Immunochemotherapy.

Immunochemotherapy mediated by thermosponge nanoparticles for synergistic anti-tumor effects.