A Multifunctional\nBiomimetic Nanoplatform for Dual\nTumor Targeting-Assisted Multimodal Therapy of Colon Cancer

The biomimetic nanoparticles (NPs) possessing abilities\nof tumor\ntargeting and multimodal therapy show great potential for efficient\ncombat of colon cancer. Herein, we developed a multifunctional biomimetic\nnanoplatform (Fe<sub>3</sub>O<sub>4</sub>@PDA@CaCO<sub>3</sub>–ICG@CM)\nbased on CaCO<sub>3</sub>-modified magnetic polydopamine (PDA) loaded\nwith indocyanine green (ICG), which was encapsulated by a mouse lymphoma\ncell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte\nfunction-associated antigen 1, LFA-1; transforming growth factor-β\nreceptor, TGF-βR; programmed cell death protein 1, PD-1; and\nfactor related apoptosis ligand, FasL). Under magnetic attraction\nand LFA-1/PD-1-mediated endocytosis, Fe<sub>3</sub>O<sub>4</sub>@PDA@CaCO<sub>3</sub>–ICG@CM efficiently targeted CT26 colon tumor cells.\nThe released calcium ion (Ca<sup>2+</sup>) from the NPs triggered\nby acidic tumor microenvironment, the enhanced photothermal effect\ncontributed by the combination of PDA and ICG, and FasL’s direct\nkilling effect together induced tumor cells apoptosis. Moreover, the\napoptosis of CT26 cells induced immunogenic cell death (ICD) to promote\nthe maturation of dendritic cells (DCs) to activate CD4<sup>+</sup>/CD8<sup>+</sup> T cells, thereby fighting against tumor cells, which\ncould further be boosted by programmed death-ligand 1 (PD-L1) blockage\nand transforming growth factor-β (TGF-β) scavenging by\nFe<sub>3</sub>O<sub>4</sub>@PDA@CaCO<sub>3</sub>–ICG@CM. As\na result, <i>in vivo</i> satisfactory therapeutic effect\nwas observed for CT26 tumor bearing-mice treated with Fe<sub>3</sub>O<sub>4</sub>@PDA@CaCO<sub>3</sub>–ICG@CM under laser irradiation\nand magnetic attraction, which could eradicate primary tumors and\nrestrain distant tumors through dual tumor targeting-assisted multimodal\ntherapy and eliciting adaptive antitumor immune response, generating\nthe immune memory for inhibiting tumor metastasis and recurrence.\nTaken together, the multifunctional biomimetic nanoplatform exhibits\nsuperior antitumor effects, providing an insightful strategy for the\nfield of nanomaterial-based treatment of cancer.