In recent years, conventional treatments including surgery, chemotherapy and radiotherapy have been the main approaches in tumour therapy. Cancer immunotherapy is a new therapeutic modality to fight cancer by harnessing the power of patients’ own immune system. Ongoing research related to these therapies has demonstrated their advantages and intrinsic limitations. Nanomaterial-based platforms are utilized in these emerging fields. In particular, a combination of other treatment methods with cancer immunotherapy to achieve precision medicine and prevent recurrence and metastasis, could improve patients’ outcome. The combined multiple treatments have superior efficacy to any monotherapy alone in producing improved anti-cancer activity. Therefore, it's necessary to summarise research advances in nanomaterial-based combination cancer immunotherapy contributing to clinical transformation. This review is based on the principles of cancer immunotherapy and the combined treatment design reflected by advances in materials science, including the structures of nanoplatforms and their underlying mechanisms towards cancer. The ultimate goals are to stimulate the design of better strategies for versatile use in the future based on biomaterial engineering methods to enhance the efficacy of combined cancer treatments, and to provide new ideas for the prospects of a synergistic cancer combination immunotherapy for clinical application transformation.

Recent advances in nanomaterial-based synergistic combination cancer immunotherapy.

Cancer immunotherapy has achieved promising clinical responses in recent years owing to the potential of controlling metastatic disease. However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non-small-cell lung cancer because of its limited expression of PD-L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid-derived suppressor cells (MDSCs). Herein, a multifunctional nanoplatform (FA-CuS/DTX@PEI-PpIX-CpG nanocomposites, denoted as FA-CD@PP-CpG) for synergistic phototherapy (photodynamic therapy (PDT), photothermal therapy (PTT) included) and docetaxel (DTX)-enhanced immunotherapy is successfully developed. The nanocomposites exhibit excellent PDT efficacy and photothermal conversion capability under 650 and 808 nm irradiation, respectively. More significantly, FA-CD@PP-CpG with no obvious side effects can remarkably inhibit the tumor growth in vivo based on a 4T1-tumor-bearing mice modal. A low dosage of loaded DTX in FA-CD@PP-CpG can promote infiltration of CTLs to improve efficacy of anti-PD-L1 antibody (aPD-L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy. Taken together, FA-CD@PP-CpG nanocomposites offer an efficient synergistic therapeutic modality in docetaxel-enhanced immunotherapy for clinical application of breast cancer.

Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers

Metal–organic frameworks have the properties of high porosity, variable pore sizes, and easy modification as drug delivery systems. In particular, ZIF-8 based on Zn2+ has been extensively studied in the medical field due to its low toxicity and good biocompatibility. This review introduces the preparation and functional modification of ZIF-8, and its application in drug delivery, focusing on the single-stimulus and multi-stimulus response release of drugs in ZIF-8 materials, the integrated role of diagnosis and treatment with ZIF-8 in cancer treatment, and its application in the synergistic therapy of multiple cancer treatment methods. We summarize the latest developments of ZIF-8 in the field of drug delivery and tumor therapy, and present the main challenges that remain to be resolved in the ZIF-8 drug delivery system.

/pdf/synthesis-and-modification-of-zif-8-and-its-application-in-1qhe0cv6ks.pdf

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

Nano-sized metal-organic frameworks: Synthesis and applications

The progressive development of zeolitic imidazolate frameworks (ZIFs), as a subfamily of metal-organic frameworks (MOFs), and their unique features, including tunable pore size, large surface area, high thermal stability, and biodegradability/biocompatibility, have made them attractive in the field of biomedicine, especially for drug delivery and biomineralization applications. The high porosity of ZIFs gives them the opportunity for encapsulating a high amount of therapeutic drugs, proteins, imaging cargos, or a combination of them to construct advanced multifunctional drug delivery systems (DDSs) with combined therapeutic and imaging capabilities. This review summarizes recent strategies on the design and fabrication of ZIF-based nansystems and their exploration in the biomedical field. First, recent developments for the adjustment of particle size, functionality, and morphology of ZIFs are discussed, which are important for achieving optimized therapeutic/theranostic nanosystems. Second, recent trends on the application of ZIF nanocarriers for the loading of diverse cargos, including anticancer medicines, antibiotic drugs, enzymes, proteins, photosensitizers, as well as imaging and photothermal agents, are investigated in order to understand how multifunctional DDSs can be designed based on the ZIF nanoparticles to treat different diseases, such as cancer and infection. Finally, prospects on the future research direction and applications of ZIF-based nanomedicines are discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.202000248

The Progress and Prospect of Zeolitic Imidazolate Frameworks in Cancer Therapy, Antibacterial Activity, and Biomineralization.

Drug-loading often suffers from tedious procedures, limited loading efficiency, slow release, and therefore a low curative effect Cancer easily recurs and metastasizes even after a solid tumor is removed Herein, we report a simple strategy with multi-drug co-loading and burst drug release for a high curative effect and anti-recurrence/metastasis CuS nanoparticles, protoporphyrin IX, and doxorubicin were added to the precursors of ZIF-8 with one-pot co-loading during the formation of ZIF-8 for chemo-, photothermal-, and photodynamic-therapy to eliminate solid tumors Negative CpG, as a kind of immune adjuvant, was adsorbed on the positive surface of ZIF-8 to inhibit the recurrence and metastasis of tumors with its long-term immune response Precision treatment with one-pot multi-drug co-loading, controllable drug delivery, and multi-modality therapy may be anticipated by this versatile strategy

/pdf/an-all-in-one-antitumor-and-anti-recurrence-metastasis-53besltslc.pdf

An “all-in-one” antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy

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An “all-in-one” antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy