Open AccessPenetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation
Author(s) -
Chen Qinjun,
He Yongqing,
Wang Yu,
Li Chao,
Zhang Yujie,
Guo Qin,
Zhang Yiwen,
Chu Yongchao,
Liu Peixin,
Chen Hongyi,
Zhou Zheng,
Zhou Wenxi,
Zhao Zhenhao,
Li Xiaomin,
Sun Tao,
Jiang Chen
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202000411
Subject(s) - immune system , tumor microenvironment , immunosuppression , immunotherapy , cancer research , infiltration (hvac) , cytotoxic t cell , immunogenic cell death , photodynamic therapy , cancer immunotherapy , medicine , immunology , chemistry , materials science , in vitro , biochemistry , organic chemistry , composite material
Lack of tumor‐infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid‐derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune‐cold” tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor‐targeting and light‐responsive‐penetrable nanoplatform (Apt/PDGs ^ s@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal–organic framework (pMOF)–based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot “immune‐cold” tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug‐loaded dendrimer de‐shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune‐related adverse effects (irAEs) induced.