Camouflaged Hybrid Cancer Cell‐Platelet Fusion Membrane Nanovesicles Deliver Therapeutic MicroRNAs to Presensitize Triple‐Negative Breast Cancer to Doxorubicin

Abstract

Camouflaged cell-membrane-based nanoparticles have gained increasing attention owing to their improved biocompatibility and immunomodulatory properties. Using nanoparticles prepared from the membranes of specific cell types or fusions derived from different cells membranes, their functional performance could be improved in several aspects. Here, cell membranes extracted from breast cancer cells and platelets are used to fabricate a hybrid-membrane vesicle (cancer cell-platelet-fusion-membrane vesicle, CPMV) loaded with therapeutic microRNAs (miRNAs) for the treatment of triple-negative breast cancer (TNBC). A clinically scalable microfluidic platform is presented for fusion of cell membranes. The reconstitution process during synthesis allows for efficient loading of miRNAs into CPMVs. Conditions for preparation of miRNA-loaded CPMVs are systematically optimized and their property of homing to source cells is demonstrated using in vitro experiments and therapeutic evaluation in vivo. In vitro, the CPMVs exhibit significant recognition of their source cells and avoided engulfment by macrophages. After systemic delivery in mice, CPMVs show a prolonged circulation time and site-specific accumulation at implanted TNBC-xenografts. The delivered antimiRNAs are sensitized TNBCs to doxorubicin, resulting in an improved therapeutic response and survival rate. This strategy has considerable potential for clinical translation to improve personalized therapy for breast cancer and other malignancies.

Erythrocyte Membrane-Camouflaged Aggregation-Induced Emission Nanoparticles for Fetal Intestinal Maturation Assessment

“…Cell membrane camouflaged nanoparticles have been shown to be biosafety reliable in vivo. − However, the safety assessment of these cell membrane camouflaged nanoparticles in pregnant mice and infants has not been confirmed. First, we evaluated the safety of M@HMSN@P in C2C12 and 293T cells.…”

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

“…In this way, the nanomaterials can be engineered to combine the RBCs' prolonged blood circulation time and immune evasion (CD47 “don't eat me” signalization) with the increased tumor specificity observed with PLTs, leukocytes, and homologous cancer cells ( Figure ). [ 151,213–215 ]…”

“…In this way, the nanomaterials can be engineered to combine the RBCs' prolonged blood circulation time and immune evasion (CD47 "don't eat me" signalization) with the increased tumor specificity observed with PLTs, leukocytes, and homologous cancer cells (Figure 6). [151,[213][214][215] Wang et al developed a hybrid membrane camouflaged nanoparticles to functionalize DOX-loaded hollow copper sulfide nanoparticles. [149] The hybrid membrane (CuS@[RBC-B16]) resulted from the fusion of RBC and melanoma cells (B16-F10 cells)-derived vesicles.…”

Pirfenidone-loaded exosomes derived from pancreatic ductal adenocarcinoma cells alleviate fibrosis of premetastatic niches to inhibit liver metastasis

“…[14][15][16] These nanocarriers still have some problems, such as their poor biocompatibility, potential cytotoxicity, short cycling times, and difficulty in crossing biological barriers. To solve these problems, some natural functional biomaterials, such as egg white 17 and cancer cell-platelet fusion membrane, 18 have been synchronously used. Among these, exosomes have attracted much attention.…”