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可生物降解的中空介孔有机硅纳米诊疗剂(HMONs)作为一种多功能平台,可用于多模式成像和光疗触发的卵巢癌细胞内溶酶体破坏。

Biodegradable hollow mesoporous organosilica nanotheranostics (HMONs) as a versatile platform for multimodal imaging and phototherapeutic-triggered endolysosomal disruption in ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Drug Deliv. 2022 Dec;29(1):161-173. doi: 10.1080/10717544.2021.2021322.

Abstract

A major impediment in the development of nanoplatform-based ovarian cancer therapy is endo/lysosome entrapment. To solve this dilemma, a hollow mesoporous organosilica-based nanoplatform (HMON@CuS/GdO) with a mild-temperature photothermal therapeutic effect and multimodal imaging abilities was successfully synthesized. HMON@CuS/GdO exhibited an appropriate size distribution, L-glutathione (GSH)-responsive degradable properties, and high singlet oxygen generation characteristics. In this study, the nanoplatform specifically entered SKOV-3 cells and was entrapped in endo/lysosomes. With a mild near infrared (NIR) power density (.5 W/cm), the HMON@CuS/GdO nanoplatform caused lysosome vacuolation, disrupted the lysosomal membrane integrity, and exerted antitumour effects in ovarian cancer. Additionally, our experiments indicated that HMON@CuS/GdO has enhanced T1 MR imaging, fluorescence (FL) imaging (wrapping fluorescent agent), and infrared thermal (IRT) imaging capacities. Using FL/MRI/IRT imaging, HMON@CuS/GdO selectively caused mild phototherapy in the cancer region, efficiently inhibiting the growth of ovarian cancer without systemic toxicity . Taken together, the results showed that these well-synthesized nanoplatforms are likely promising anticancer agents to treat ovarian cancer and show great potential for biomedical applications.

摘要

基于纳米平台的卵巢癌治疗的一个主要障碍是内体/溶酶体捕获。为了解决这一难题,成功合成了一种具有温和温度光热治疗效果和多模态成像能力的基于中空介孔有机硅的纳米平台(HMON@CuS/GdO)。HMON@CuS/GdO 表现出适当的粒径分布、L-谷胱甘肽(GSH)响应性降解特性和高单线态氧生成特性。在这项研究中,纳米平台特异性进入 SKOV-3 细胞并被内体/溶酶体捕获。在温和的近红外(NIR)功率密度(.5 W/cm)下,HMON@CuS/GdO 纳米平台导致溶酶体空泡化,破坏溶酶体膜完整性,并对卵巢癌发挥抗肿瘤作用。此外,我们的实验表明,HMON@CuS/GdO 具有增强的 T1 磁共振成像、荧光(FL)成像(包裹荧光剂)和红外热(IRT)成像能力。通过 FL/MRI/IRT 成像,HMON@CuS/GdO 选择性地在癌症区域引起温和的光疗,有效地抑制卵巢癌的生长而没有全身毒性。总之,这些结果表明,这些精心合成的纳米平台可能是治疗卵巢癌的有前途的抗癌药物,并且在生物医学应用中具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263c/8725973/a51570e783c1/IDRD_A_2021322_F0001_C.jpg

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