Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, Delaware, 19716.
Department of Materials Science & Engineering, University of Delaware, 201 DuPont Hall, Newark, Delaware, 19716.
J Biomed Mater Res A. 2019 Aug;107(8):1702-1712. doi: 10.1002/jbm.a.36685. Epub 2019 Apr 9.
Triple-negative breast cancer (TNBC) accounts for 15-25% of breast cancer cases and lacks expression of the three most common receptors seen on other subtypes of breast cancer. This lack of expression makes TNBC unsusceptible to currently available targeted or hormonal therapies, so new treatment strategies are desperately needed. Photothermal therapy (PTT), which utilizes nanoparticles (NPs) embedded in tumors as exogenous energy absorbers to convert externally applied near-infrared (NIR) light into heat to ablate cancer cells, has shown promise as an alternative strategy. However, it typically uses gold-based NPs that will remain in the body for extended period of time with unknown long-term health effects. To enable PTT with biodegradable, polymeric NPs, we encapsulated the NIR-absorbing dye IR820 in poly(lactic-co-glycolic acid) (PLGA) NPs. We characterized the physicochemical properties of these IR820-loaded PLGA NPs and evaluated their performance as PTT agents using both in vitro and in vivo models of TNBC. The results demonstrate that these NPs are potent mediators of PTT that induce cell death primarily through apoptosis to effectively hinder the growth of TNBC tumors. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1702-1712, 2019.
三阴性乳腺癌(TNBC)占乳腺癌病例的 15-25%,并且缺乏其他乳腺癌亚型中常见的三种受体的表达。这种缺乏表达使 TNBC 对目前可用的靶向或激素治疗方法不敏感,因此迫切需要新的治疗策略。光热疗法(PTT)利用嵌入肿瘤中的纳米颗粒(NPs)作为外源能量吸收剂,将外部施加的近红外(NIR)光转化为热量来消融癌细胞,已被证明是一种有前途的替代策略。然而,它通常使用金基 NPs,这些 NPs 将在体内停留很长时间,其未知的长期健康影响。为了能够使用可生物降解的聚合物 NPs 进行 PTT,我们将近红外吸收染料 IR820 封装在聚(乳酸-共-乙醇酸)(PLGA)NPs 中。我们对这些负载有 IR820 的 PLGA NPs 的物理化学性质进行了表征,并使用 TNBC 的体外和体内模型评估了它们作为 PTT 试剂的性能。结果表明,这些 NPs 是 PTT 的有效介导物,主要通过细胞凋亡诱导细胞死亡,有效地抑制 TNBC 肿瘤的生长。 © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A:107A:1702-1712,2019。