基于铁掺杂红色碳点和滚环扩增技术构建的靶向药物递送DNA纳米组装体

Iron-doped Red Carbon Dot and Rolling Circle Amplification-mediated DNA Nano-assemblies for Targeted Drug Delivery

摘要

以滚环扩增（RCA）产生的长单链脱氧核糖核酸（DNA）为支架， 开发了一种基于RCA的组装技术. 将该支架与具有不同功能的短链组装成多价适配体， 再与铁掺杂的红色碳点（Fe-CDs）结合， 构建了多价适配体核酸组装体-Fe-CDs-阿霉素（AFD）纳米平台， 用于精准的联合癌症治疗. 在AFD纳米平台中， MUC1适配体能够发挥高效的靶向能力， 在精准作用于癌细胞的同时减少对正常细胞的伤害. Fe-CDs具有类过氧化物酶活性， 可将过氧化氢催化分解为羟基自由基， 从而实现化学动力学治疗. 此外， AFD通过其中丰富的CG碱基对能够高效负载阿霉素（DOX）. 当多价适配体凭借高效的靶向性进入癌细胞后， 会释放负载的Fe-CDs和DOX， 实现对癌细胞的有效杀灭.

Abstract

A rolling circle amplification(RCA)-based assembly technique was proposed, which utilized the long single-stranded DNA produced by RCA as a scaffold. This scaffold was assembled with functional short strands into multivalent aptamers and subsequently combined with iron-doped red carbon dots(Fe-CDs) to construct a multivalent aptamer-based nanoplatform, termed assembly-Fe-CDs-doxorubicin(AFD), for precision combination cancer therapy. In the AFD nanoplatform, the MUC1 aptamer exerted efficient targeting capabilities, precisely acting on cancer cells while minimizing collateral damage to normal cells. The Fe-CDs possessed peroxidase-like activity, which catalyzed the decomposition of hydrogen peroxide(H₂O₂) into hydroxyl radicals(·OH), thereby achieving chemodynamic therapy(CDT). Furthermore, the abundant CG base pairs within the AFD structure enabled the high-efficiency loading of doxorubicin(DOX). Upon entering cancer cells via highly efficient targeting, the multivalent aptamers released the encapsulated Fe-CDs and DOX, facilitating the effective eradication of cancer cells. In summary, this multivalent aptamer nanoplatform based on DNA and Fe-CDs provided a promising and highly selective approach for enhancing the efficacy of cancer treatment.

关键词

滚环扩增 / 碳点 / 多价适配体 / 药物递送 / 癌症治疗

Key words

Rolling circle amplification / Carbon dot / Polyvalent aptamer / Drug delivery / Cancer therapy

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基金资助

山东省自然科学基金(ZR2022MB148)

山东省自然科学基金(ZR2023MB148)

山东省优质教育教学资源项目(SDYAL2024044)

中国石油大学(华东)教改项目(YJG2023023)