Tumor microenvironment-specific nanoparticles activatable by stepwise transformation

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• 作者：Hyewon Ko^a ; Soyoung Son^a ; Jueun Jeon^b ; Thavasyappan Thambi^b ; Seunglee Kwon^b ; Yee Soo Chae^c ; Young Mo Kang^c ; Jae Hyung Park^a ; ^b ; ^{jhpark1@skku.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Stepwise transformation ; Biostability ; Tumor microenvironment ; Drug delivery
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 July 2016
• 年：2016
• 卷：234
• 期：Complete
• 页码：68-78
• 全文大小：1812 K

文摘

In an attempt to develop the tumor-targeted nanocarrier which can surmount major challenges for in vivo application, we prepared tumor microenvironment-specific nanoparticles which can be sequentially activated at the extracellular and intracellular levels of tumor tissue by stepwise transformation. This polymeric nanoparticle has been prepared using an amphiphilic polyethyleneimine derivative with the pH-responsive charge-convertible moiety and the reduction-responsive crosslink. Once reaching the tumor tissue in vivo after systemic administration, the surface charge of this nanoparticle can be converted from negative to positive by recognizing the mildly acidic extracellular matrix of tumor, allowing for the enhanced cellular uptake. After the cellular uptake, the nanoparticle can selectively release the drug at the intracellular level since it has the chemically crosslinked core by the disulfide bond which is cleaved in intracellular reductive environment. The tumor microenvironment-specific nanoparticle shows the high tumor targetability and dramatically improves the antitumor efficacy of the drug.