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Nanoparticle‐Enabled Dual Modulation of Phagocytic Signals to Improve Macrophage‐Mediated Cancer Immunotherapy
Author(s) -
Zhang YaRu,
Luo JiaQi,
Zhang JingYang,
Miao WeiMin,
Wu JiaSi,
Huang Hua,
Tong QiSong,
Shen Song,
Leong Kam W.,
Du JinZhi,
Wang Jun
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202004240
Subject(s) - cd47 , phagocytosis , calreticulin , macrophage , cancer immunotherapy , immunotherapy , cancer research , cancer cell , cell , microbiology and biotechnology , cancer , chemistry , biology , immunology , immune system , in vitro , biochemistry , genetics , endoplasmic reticulum
Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti‐phagocytic signals (e.g., CD47 molecules) on their surface. To promote phagocytosis of macrophages, a pro‐phagocytic nanoparticle (SNPA CALR&aCD47 ) that concurrently carries CD47 antibody (aCD47) and a pro‐phagocytic molecule calreticulin (CALR) is constructed to simultaneously modulate the phagocytic signals of macrophages. SNPA CALR&aCD47 can achieve targeted delivery to tumor cells by specifically binding to the cell‐surface CD47 and block the CD47‐SIRPα pathway to inhibit the “don't eat me” signal. Tumor cell‐targeted delivery increases the exposure of recombinant CALR on the cell surface and stimulates an “eat me” signal. Simultaneous modulation of the two signals enhances the phagocytosis of 4T1 tumor cells by macrophages, which leads to significantly improved anti‐tumor efficacy in vivo. The findings demonstrate that the concurrent blockade of anti‐phagocytic signals and activation of pro‐phagocytic signals can be effective in macrophage‐mediated cancer immunotherapy.