Two-dimensional LDH nanodisks modified with hyaluronidase enable enhanced tumor penetration and augmented chemotherapy

• 作者: Gaoming Li Yu Fan Lizhou Lin Rong Wu Mingwu Shen Xiangyang Shi
• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: ARTICLES
• 页码范围: 817-826
• 页数: 10页
• 语种: 英文

摘要

The condensed tumor extracellular matrix (ECM) consisting of cross-linked hyaluronic acid (HA) is one of the key factors that result in the aberrant tumor microenvironment and severely impair drug delivery and tumor penetration.Herein,we report a simple design of a hyaluronidase (HAase)-modified layered double hydroxide (LDH) nanoplatform loaded with anticancer drug doxorubicin (DOX) for enhanced tumor penetration and augmented chemotherapy.In our approach,LDH nanodisks were synthesized via a co-precipitation method,modified with HAase by electrostatic attraction,and finally physically loaded with DOX.The formulated DOX/LDH-HAase complexes show a high DOX loading percentage of 34.2％ with good colloidal stability,retain 86.1％ of the enzyme activity,and release DOX in a pH-responsive manner having a faster release rate under slightly acidic tumor microenvironment than that under a physiological condition.With the catalytic activity of HAase to digest the HA nearby the cancer cells,the developed DOX/LDH-HAase complexes enable more significant uptake by cancer cells and penetration in 3-dimensional tumor spheroids than enzyme-free DOX/LDH complexes,thus displaying much better antitumor efficacy in vitro than the latter.The more significant tumor penetration and inhibition of the DOX/LDH-HAase complexes than that of the DOX/LDH complexes was further demonstrated by in vivo tumor imaging and therapeutic activity assessments.Our study suggests a unique nanomedicine platform combined with both anticancer drug and enzyme for improved tumor penetration and chemotherapy,which is promising for effective chemotherapy of different types of stroma-rich tumors.