Tumor-Activated Size-Enlargeable Bioinspired Lipoproteins Access Cancer Cells in Tumor to Elicit Anti-Tumor Immune Responses.

Abstract

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.

• Authors: Jie Li, Hong Wang, Yuqi Wang, Xiang Gong, Xiaoxuan Xu, Xianyi Sha, Ao Zhang, Zhiwen Zhang, Yaping Li
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 32 Issue 38 Pg. e2002380 (Sep 2020) ISSN: 1521-4095 [Electronic] Germany
• PMID: 33252171 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley‐VCH GmbH.

Chemical References

• Lipoproteins
• Prodrugs
• Oxaliplatin

Topics

• Animals
• Biomimetic Materials (chemistry, metabolism, pharmacology)
• Cell Line, Tumor
• Humans
• Hydrophobic and Hydrophilic Interactions
• Immunogenic Cell Death (drug effects)
• Immunotherapy (methods)
• Lipoproteins (chemistry, metabolism, pharmacology)
• Oxaliplatin (chemistry, metabolism)
• Prodrugs (chemistry, metabolism)