A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD‐1/PD‐L1 Axis

Abstract

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.

Nanomedicines based on nanoscale metal-organic frameworks for cancer immunotherapy

“…As PD-L1 expressed by cancer cells can actually inhibit antigenspecific CTLs from recognizing and killing tumor cells and even drive CTLs into apoptosis, these coated nMOFs were combined with in situ vaccination with a monoclonal antibody against PD-1. This approach increased the number of infiltrating CD8 + T cells and the production of interleukin-12 and tumor necrosis factor-α, inhibiting the growth and metastasis of murine melanoma tumor cells in mice [62].…”

Recent Advances of Cell Membrane‐Coated Nanomaterials for Biomedical Applications

“…[102] Many groups have investigated that introducing tumor cell membranes to nanoparticles could realize specific recognition and increase the uptake amount of nanoparticles via receptor-mediated endocytosis, leading to enhanced therapeutic efficiency, such as loading nano-photosensitizer (PCN-224) for photodynamic therapy, [103] photothermal regents (ICG) for fluorescence/photoacoustic imaging and photothermal therapy, [104] antineoplastic drug for chemotherapy, [105] host-specific transfection and magnetic resonance imaging, [106] and combined therapy. [107] On the other hand, diverse types of tumor cell membrane have been used for homotypic targeting, such as 4T1 cell membrane, [108] human breast cell (MCF-7) membrane, [109] human cervix carcinoma cell (Hela) membrane, [106] murine melanoma (B16F10) cell membrane, [110] human glioblastoma (U87) cell membrane, [111] head and neck squamous cell carcinoma (HNSCC) membrane [112] and so on. As a rule of thumb, the separation and purification of tumor cell membrane-coated nanoparticles from empty cell membrane by centrifugation are difficult and timeconsuming.…”

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

“…To enhance the efficacy of anti-PD-1 antibodies, many strategies involving hypoxia alleviation and combination with other immunomodulatory drugs have been proposed. Zou et al prepared a multifunctional biomimetic nanoplatform containing zeolitic imidazolate framework (ZIF)-8 coated with a tumor cell membrane as the guidance part and antigen stimulation to codeliver catalase and doxorubicin [ 35 ]. Oxygen generation by catalysis of catalase could alleviate hypoxic conditions and enhance the antitumor effects of doxorubicin.…”