DNA 纳米组装修饰的聚多巴胺@二氧化锰纳米颗粒：增强 miRNA-21 下调以逆转乳腺癌耐药
DNA Nanoassembly Modified Polydopamine@MnO2 Nanoparticles: Enhancement of miRNA-21 Downregulation for Reversal of Breast Cancer Drug-Resistance
耐药是乳腺癌治疗的一大难题，下调致癌微小 RNA（miRNA）是潜在策略，但传统核酸药物稳定性差。研究者以 miRNA-21 为靶点、耐药乳腺癌细胞为模型，构建了球形核酸型递药系统：Y 形 DNA 纳米结构定向固定在聚多巴胺@二氧化锰纳米颗粒上，内含两段切割 miRNA-21 的 DNA 酶和肿瘤靶向适配体，并载入阿霉素。该系统提高了 DNA 酶稳定性、自行供应辅因子、靶向肿瘤，还能缓解缺氧、消耗谷胱甘肽、产生活性氧并光热转换。结果显示细胞内 miRNA-21 被有效下调，阿霉素可控释放，加激光处理后癌细胞存活率降至 3% 以下，肿瘤生长抑制率达 86%。
为什么推荐给您：多模块纳米递药平台在细胞和动物模型验证，属早期转化研究。
不需要生物学背景，多打比方
正在获取全文并生成讲解（拿不到全文就依据摘要），大约需要 30–60 秒…
已等待 0 秒
这篇还没有动画
动画会把研究的流程、作用机制和关键结果一步一步演示出来，每一步都标明出自原文哪里。制作大约需要 30–60 秒。
摘要Abstract
Downregulating oncogenic microRNAs (miRNAs) is an attractive strategy for reversing drug resistance in cancer therapy. Compared to antisense, DNAzyme (Dz) possesses advantages such as recyclability and stability. However, it still suffers from insufficient stability and inadequate endogenous cofactors. Herein, by using miRNA-21 (miR-21) as target, MCF-7/ADR as tumor model, a multi-modality, polyvalent, Spherical Nucleic Acids (SNAs)-type drug delivery system (DDS) was developed. A Y-DNA nanoassembly was synthesized, and directional immobilized on polydopamine@MnO2 (PDM) nanoparticles. The Y-DNA contains two Dz sequences for cleaving miR-21, and a tumor-targeting aptamer. Doxorubicin was loaded at a loading rate of 23.33%. The DDS dramatically improved the Dz stability, self-supplied cofactors, efficiently targeted tumor tissues and cells. Additionally, it relieved hypoxia, depleted glutathione, generated reaction oxygen species, and transferred near-infrared light to heat. Consequently, highly responsive, and DNase resistant cleavage of miR-21 was realized. Intracellular miR-21 was efficiently downregulated. Doxorubicin was controllably and efficiently released. With the PDM@Y-DNA@D (Laser+) treatment, the cancer cell viability lowered to ≤3%, and tumor growth inhibition reached to 86%. Molecular mechanisms involved in the drug resistance reversal were investigated. The DDS provides a promisingly transformable therapeutic platform for drug resistant cancers, and for targeting other and multiple oncogenic miRNAs.