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Tumor‐Activated Size‐Enlargeable Bioinspired Lipoproteins Access Cancer Cells in Tumor to Elicit Anti‐Tumor Immune Responses
Author(s) -
Li Jie,
Wang Hong,
Wang Yuqi,
Gong Xiang,
Xu Xiaoxuan,
Sha Xianyi,
Zhang Ao,
Zhang Zhiwen,
Li Yaping
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202002380
Subject(s) - immune system , immunotherapy , cancer immunotherapy , immunogenic cell death , cancer research , tumor microenvironment , materials science , cancer cell , cancer , drug delivery , immunology , pharmacology , medicine , nanotechnology
The limited lymphocytes infiltration and immunosuppression in tumor are the major challenges of cancer immunotherapy. The use of immunogenic cell death (ICD)‐inducing agents has potential to potentiate antitumor immune responses, but is tremendously hampered by the poor delivery efficiency. Herein, a tumor‐activated size‐enlargeable bioinspired lipoprotein of oxaliplatin (TA‐OBL) is designed to access cancer cells and boost the ICD‐induced antitumor immunity for synergizing immune‐checkpoint blockades (ICBs)‐mediated immunotherapy. TA‐OBL is constructed by integrating a legumain‐sensitive melittin conjugate for improving intratumoral permeation and cancer cell accessibility, a pH‐sensitive phospholipid for triggering size‐enlargement and drug release in intracellular acidic environments, a nitroreductase‐sensitive hydrophobic oxaliplatin prodrug (N‐OXP) for eliciting antitumor immunity into the bioinspired nano‐sized lipoprotein system. TA‐OBL treatment produced robust antitumor immune responses and its combination with ICBs demonstrates strong therapeutic benefits with delayed tumor growth and extended survival rate, making it a promising delivery nanoplatform to elicit antitumor immunity for cancer immunotherapy.