期刊
出版社
ELSEVIER
DOI: 10.1016/j.msec.2020.111004
关键词
Bromelain; Ortho ester; Nanoparticles; Drug delivery
资金
- National Natural Science Foundation of China [51503001, 51803001, 51603001]
- Research Foundation of Education Department of Anhui Province of China [K120438029, KJ2018ZD003, KJ2018A0006]
Dense extracellular matrix (ECM) is a primary obstacle that restrains the permeation of therapeutic drugs in tumor tissues. Degrading ECM with bromelain (Br) to increase drug penetration is an attractive strategy to enhance antitumor effects. However, the poor stability in circulation and potential immunogenicity severely limit their applications. In this work, a novel pH-sensitive nanocarrier was prepared by crosslinking Br with an ortho ester-based crosslink agent, and Br still retained a certain ability to degrade ECM after crosslinking. The nanoparticles showed higher DOX release rate than non-sensitive nanoparticles, and DOX release amount reached to 86% at pH 5.5 within 120 h. In vivo experiments revealed that the pH-sensitive nanoparticles could be degraded in mildly acidic condition, and the released Br further promoted nanoparticles penetration in tumor parenchyma via in situ hydrolysis of ECM. Furthermore, Br itself could inhibit the proliferation of tumor cells at high concentration, and produce synergistic antitumor effects with DOX. Finally, tumor growth inhibition of these nanoparticles reached to 62.5%. Overall, the bromelain-based pH-sensitive nanoparticles can be potential drug carriers for efficient drug delivery and tumor treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据