Hybrid membrane-camouflaged photothermal immunomodulatory nanoparticle inhibits colorectal cancer growth and metastasis.

Photothermal therapy (PTT) alone is insufficient for the complete elimination of malignant cells, which may lead to recurrence and metastasis. Thus, PTT is usually used in combination with immunomodulatory therapy. Herein, hybrid cell membrane biomimetic nanoparticle was developed by fusing a Raw 264.7 macrophage-derived extracellular vesicle membrane (Rm) and a CT26 cell membrane (Cm) to encapsulate imiquimod (R837)-loaded polydopamine (PDA)-modified Fe(3)O(4) nanoparticle (R837@MfNP). R837@MfNP displayed distinct core-shell structure, spherical shape, and well dispersion, with particle size of 136.0 ± 2.0 nm, zeta potential of -15.7 ± 0.8 mV, loading efficiency of 9.8 ± 0.4% and PDI of 0.18 ± 0.03. Owing to homologous targeting and immune escape by hybrid cell membranes, R837@MfNP exhibited remarkable targeting capacity against colorectal cancer (CRC) cells. Once they reached the tumour site, the PDA-modified Fe(3)O(4) nanoparticle (Fe(3)O(4)@PDA) and R837 were rapidly released in the acidic tumour microenvironment. Then, Fe(3)O(4)@PDA triggered photothermal effects to kill tumour cells and induce immunogenic cell death under 808 nm NIR light irradiation (∼50 °C). Subsequently, assisted by the immune adjuvant R837, the maturation rate of dendritic cells (DCs) was notably increased. In CRC cancer mouse models, R837@MfNP-mediated PTT eradicated in situ tumours upon laser irradiation and exhibited significant therapeutic effectiveness in both distant tumours and lung metastases by increasing DC maturation in the lymph nodes and promoting the infiltration of CD8(+) T cells into tumours. Overall, R837@MfNP-mediated PTT effectively inhibited tumour growth and metastasis by increasing the T-cell antitumour immune response, providing a novel hybrid membrane-camouflaged biomimetic nanodelivery system for synergistic treatment with PTT and immunotherapy for CRC. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Imiquimod (R837, PubChem CID: 57469), Polydopamine (PDA), Iron (II,III) oxide (Fe₃O₄, PubChem CID: 16211978), Coumarin 6 (C6, PubChem CID: 100334), IR775 chloride (PubChem CID: 44465046).