College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.
School of Pharmacy, Xinxiang Medical University, No. 601, Jinsui Road, Xinxiang 453003, China.
ACS Appl Mater Interfaces. 2021 Apr 7;13(13):14894-14910. doi: 10.1021/acsami.0c23073. Epub 2021 Mar 26.
Multidrug resistance (MDR) is identified as a major impediment to the efficient chemotherapy of cancer, and considerable endeavors have been devoted to reverse MDR containing structuring varieties of multifunctional nanocarriers. Here, a specially light-activated hollow mesoporous silica nanocontainer with an in situ-synthesized Au nanorod (AuNR) core and a surface-modified hairpin structure DNA gatekeeper is reported for treating MDR tumor cells. In this system, the AuNR only fills part of the space in hollow mesoporous silica due to its controllable size, and the remaining space is used to load enough DOX. By controlling the near-infrared (NIR) laser intensity and exposure duration, the configuration of hairpin-structured DNA ( = 51.4 °C) can change reversibly and then trigger the controllable intracellular release of DOX, leading to a significantly enhanced chemotherapeutic efficacy and adjustable photothermal treatment for multidrug-resistant cancer cells. The in vitro experiments showed that this system could effectively overcome the MDR of HepG2-adm cells (a MDR cell line of human hepatocarcinoma cells) by the increased concentration of DOX intracellularly and the photothermal conversion of AuNRs, even at a low concentration (e.g., 30 μg mL). Therefore, this NIR-triggered chemo-photothermal synergistic treatment system can be used as a promising efficient strategy in reversing the multidrug resistance for cancer therapy.
多药耐药性（MDR）被认为是癌症高效化疗的主要障碍，人们已经投入了大量精力来构建具有逆转多药耐药性（MDR）功能的多功能纳米载体。在这里，我们报道了一种特殊的光激活中空介孔硅纳米容器，其具有原位合成的金纳米棒（AuNR）核和表面修饰的发夹结构 DNA 门控。该系统中，由于 AuNR 的可控尺寸，AuNR 仅填充中空介孔硅的部分空间，而剩余的空间则用于装载足够的 DOX。通过控制近红外（NIR）激光强度和照射时间，发夹结构 DNA 的构象可以可逆地改变，然后触发 DOX 的可控细胞内释放，从而显著提高多药耐药性癌细胞的化学治疗效果和可调光热治疗效果。体外实验表明，该系统可以通过增加细胞内 DOX 的浓度和 AuNR 的光热转化，有效克服 HepG2-adm 细胞（人肝癌细胞的 MDR 细胞系）的 MDR，即使在低浓度下（例如，30μg mL）。因此，这种 NIR 触发的化疗-光热协同治疗系统可以作为一种有前途的高效策略，用于逆转癌症治疗中的多药耐药性。
