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Microenvironment‐Induced In Situ Self‐Assembly of Polymer–Peptide Conjugates That Attack Solid Tumors Deeply
Author(s) -
Cong Yong,
Ji Lei,
Gao YuJuan,
Liu FuHua,
Cheng DongBing,
Hu Zhiyuan,
Qiao ZengYing,
Wang Hao
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900135
Subject(s) - peptide , in vivo , conjugated system , conjugate , moiety , chemistry , penetration (warfare) , biophysics , in situ , polymer , drug delivery , nanotechnology , materials science , stereochemistry , biochemistry , organic chemistry , mathematical analysis , mathematics , microbiology and biotechnology , operations research , engineering , biology
In cancer treatment, the unsatisfactory solid‐tumor penetration of nanomaterials limits their therapeutic efficacy. We employed an in vivo self‐assembly strategy and designed polymer–peptide conjugates (PPCs) that underwent an acid‐induced hydrophobicity increase with a narrow pH‐response range (from 7.4 to 6.5). In situ self‐assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC 50 values of PPCs) enabled drug delivery deeper into the tumor. A cytotoxic peptide KLAK, decorated with the pH‐sensitive moiety cis ‐aconitic anhydride (CAA), and a cell‐penetrating peptide TAT were conjugated onto poly(β‐thioester) backbones to produce PT‐K‐CAA, which can penetrate deeply into solid tumors owing to its small size as a single chain. During penetration in vivo, CAA responds to the weak acid, leading to the self‐assembly of PPCs and the recovery of therapeutic activity. Therefore, a deep‐penetration ability for enhanced cancer therapy is provided by this in vivo assembly strategy.