Self-assembled nanoparticles formed: Via complementary nucleobase pair interactions between drugs and nanocarriers for highly efficient tumor-selective chemotherapy

Fasih Bintang Ilhami, Ai Chung, Yihalem Abebe Alemayehu, Ai Wei Lee, Jem Kun Chen, Juin Yih Lai, Chih Chia Cheng

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

We report a significant breakthrough in the development of complementary hydrogen-bonded drug-carrier systems, namely the construction of self-assembled nanoparticles with desirable functionalities conferred by the presence of stable complementary uracil-adenine (U-A) hydrogen bonding interactions between the drug and carrier complex. Herein, an adenine-functionalized rhodamine derivative (A-R6G) was successfully synthesized, and exhibited a variety of interesting physical properties including unique hydrophobicity, hydrogen bond-modulated green-fluorescence behavior and potent tumor-cell specific cytotoxicity. A-R6G strongly associates with uracil end-capped difunctional poly(propylene glycol) (BU-PPG) to spontaneously form spherical nanoparticles in aqueous solution due to the complementary U-A interactions between the drug and the carrier. These nanoparticles possess several interesting physical properties, such as ultrahigh drug loading content (up to 84.3%), a wide-range tunable drug loading ratio, high A-R6G-encapsulation stability in serum-rich culture media and pH/temperature-sensitive controlled drug release; these properties are very rare in drug-loaded nanoparticles, but are extremely desirable for drug-delivery applications based on polymeric micelles. Surprisingly, A-R6G-loaded nanoparticles exhibited selective cytotoxicity against cancer cells but had no effects on normal cells, whereas control rhodamine 6G-loaded nanoparticles displayed potent non-selective cytotoxicity, suggesting that the U-A interactions within the nanoparticles critically enhance the tumor-selective cytotoxicity of A-R6G towards cancer cells. Importantly, fluorescence imaging and flow cytometric assays confirmed that A-R6G-loaded nanoparticles were selectively delivered into cancer cells via an endocytic pathway and subsequently induced apoptotic cell death, but had minimal cytotoxic effects on normal cells. Thus, this complementary drug-carrier system has the ability to achieve targeted cancer chemotherapy with high therapeutic efficacy and safety. This journal is
原文英語
頁(從 - 到)5442-5451
頁數10
期刊Materials Chemistry Frontiers
5
發行號14
DOIs
出版狀態已發佈 - 7月 21 2021

ASJC Scopus subject areas

  • 材料科學(全部)
  • 材料化學

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