Synergistically Enhanced Mucoadhesive and Penetrable Polypeptide Nanogel for Efficient Drug Delivery to Orthotopic Bladder Cancer  

作　　者：Hui Guo Faping Li Heping Qiu Weiguo Xu Pengqiang Li Yuchuan Hou Jianxun Ding Xuesi Chen 

机构地区：[1]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,5625 Renmin Street,Changchun 130022,China [2]Department of Urinary Surgery,The First Hospital of Jilin University,71 Xinmin Street,Changchun 130021,China

出　　处：《Research》2020年第1期1659-1672,共14页研究（英文）

基　　金：The study was financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51833010,and 51803006);the Science and Technology Development Program of Jilin Province(Grant No.20200404182YY);the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019005).

摘　　要：Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer(BC)from local recurrence in the clinic.However,due to rapid urine excretion and barrier protection of the bladder wall,the clinical performances of chemotherapeutic drugs are severely compromised.In the present work,a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(R_(9)-PEG-P(LP-co-LC))was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall.PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin(HCPT)-loaded R_(9)-PEG-P(LP-co-LC)(i.e.,R_(9)NG/HCPT)and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R_(9)and negatively charged bladder mucosa.Besides,R_(9),as a cell-penetrating peptide,efficiently penetrated through the cell membrane and delivered carried cargo.The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment.As an advanced chemotherapeutic nanoformulation,the smart R_(9)NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo,indicating its great potential in the clinical intravesical BC chemotherapy.

关 键 词：BLADDER CHEMOTHERAPY DISULFIDE 

分 类 号：R737.14[医药卫生—肿瘤]