Open AccessMucoadhesive Cationic Polypeptide Nanogel with Enhanced Penetration for Efficient Intravesical Chemotherapy of Bladder Cancer
Author(s) -
Guo Hui,
Li Faping,
Xu Weiguo,
Chen Jinjin,
Hou Yuchuan,
Wang Chunxi,
Ding Jianxun,
Chen Xuesi
Publication year - 2018
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.201800004
Subject(s) - nanogel , bladder cancer , in vivo , chemotherapy , doxorubicin , cancer research , medicine , urology , pharmacology , chemistry , drug delivery , cancer , biology , organic chemistry , microbiology and biotechnology
Initially, chemotherapy is effective for treatment of bladder cancer after transurethral resection of the bladder. However, certain patients progressively become unresponsive after multiple treatment cycles, which results from the rapid and almost complete excretion of clinically used formulations of antineoplastic agents with urinary voiding. Improving the mucoadhesiveness and penetrability of chemotherapeutic drugs are key factors in treatment of advanced bladder cancer. Here, a smart disulfide‐crosslinked polypeptide nanogel of poly( l ‐lysine)–poly( l ‐phenylalanine‐ co ‐ l ‐cystine) (PLL–P(LP‐ co ‐LC)) is developed to deliver 10‐hydroxycamptothecin (HCPT) for treatment of orthotopic bladder cancer. The positively charged PLL–P(LP‐ co ‐LC) can significantly prolong the retention period and enhance the tissue permeability of HCPT within the bladder wall of rat. Moreover, the reduction‐responsive polypeptide nanogel (i.e., NG/HCPT) possesses the capability to accurately and rapidly deliver HCPT in bladder cancer cells. NG/HCPT can significantly inhibit proliferation of human bladder cancer 5637 cells in vitro and enhance antitumor activity toward an orthotopic rat bladder cancer model in vivo. This work demonstrates that the smart polypeptide nanogel may function as a promising drug‐delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.