Reactive oxygen species and enzyme dual-responsive biocompatible drug delivery system for targeted tumor therapy

JOURNAL OF CONTROLLED RELEASE

卷:324

Article

Zhao, Ning¹  Ding, Bingbing¹  Zhang, Ying²  Klockow, Jessica L.¹  Lau, Ken¹  Chin, Frederick T.¹  Cheng, Zhen¹  Liu, Hongguang² 

[1] Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Palo Alto, CA 94305 USA

[2] Northeastern Univ, Coll Life & Hlth Sci, Inst Mol Med, Shenyang 110000, Peoples R China

关键词: Cancer therapy;    Drug delivery;    Gold nanocluster;    Reactive oxygen species;    Trypsin;   

DOI  :  10.1016/j.jconrel.2020.05.031

来源: Elsevier

【 摘 要 】

Spurred by newly developed drug delivery systems (DDSs), side effects of cancer chemotherapy could be reduced by using multifunctional nanoplatforms. However, the facile synthesis of effective DDSs remains a challenge. Here, a six-arginine-tailed anti-epidermal growth factor receptor (EGFR) affibody was employed to easily synthesize the highly reactive oxygen species (hROS)- and trypsin-responsive 11-mercaptoundecanoic acid-modified gold nanoclusters (MUA-Au NCs) for tumor-targeted drug delivery. The polyarginine moiety of affibody sealed methotrexate (MTX)-loaded MUA-Au NCs through charge effect, as well as leaving the rest targeting fragment of the affibody to specifically bind tumor overexpressed EGFR. As the shell of MUA-Au NCs-MTX-Affibody (MAMA), polyarginine chains of affibody could be digested by trypsin, helping to release MTX from MAMA. The released MTX accelerated destroying MUA-Au NCs through inducing the generation of hROS. Specifically targeting EGFR-overexpressed tumors, quickly delivering a sufficient amount of drug to the tumor, subsequently increasing the local MTX and hROS levels, and safely eliminating the biocompatible structure from kidney, endowed MAMA greater treatment effectiveness and lower side effect than chemotherapy, especially in pancreatic cancer due to its high trypsin level. This simply fabricated DDS may find applications in high effective cancer therapy, especially for tumors with high trypsin activity.

【 授权许可】

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