Chu Chun, Bao Zhihong, Sun Meng, Wang Xiaowei, Zhang Hongyan, Chen Weiguo, Sui Yang, Li Ji, Zhuang Yuanyuan, Wang Dongkai
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Pharmaceutics. 2020 Jul 17;12(7):675. doi: 10.3390/pharmaceutics12070675.
The combination of chemotherapy and phototherapy has attracted increasing attention for cancer treatment in recent years. In the current study, porous PdPt bimetallic nanoparticles (NPs) were synthesized and used as delivery carriers for the anti-cancer drug doxorubicin (DOX). DOX@PdPt NPs were modified with thiol functionalized hyaluronic acid (HA-SH) to generate DOX@PdPt@HA NPs with an average size of 105.2 ± 6.7 nm. Characterization and in vivo and in vitro assessment of anti-tumor effects of DOX@PdPt@HA NPs were further performed. The prepared DOX@PdPt@HA NPs presented a high photothermal conversion efficiency of 49.1% under the irradiation of a single 808 nm near-infrared (NIR) laser. Moreover, NIR laser irradiation-induced photothermal effect triggered the release of DOX from DOX@PdPt@HA NPs. The combined chemo-photothermal treatment of NIR-irradiated DOX@PdPt@HA NPs exerted a stronger inhibitory effect on cell viability than that of DOX or NIR-irradiated PdPt@HA NPs in mouse mammary carcinoma 4T1 cells in vitro. Further, the in vivo combination therapy, which used NIR-irradiated DOX@PdPt@HA NPs in a mouse tumor model established by subcutaneous inoculation of 4T1 cells, was demonstrated to achieve a remarkable tumor-growth inhibition in comparison with chemotherapy or photothermal therapy alone. Results of immunohistochemical staining for caspase-3 and Ki-67 indicated the increased apoptosis and decreased proliferation of tumor cells contributed to the anti-tumor effect of chemo-photothermal treatment. In addition, DOX@PdPt@HA NPs induced negligible toxicity in vivo. Hence, the developed nanoplatform demonstrates great potential for applications in photothermal therapy, drug delivery and controlled release.
近年来,化疗与光疗相结合在癌症治疗中受到越来越多的关注。在本研究中,合成了多孔钯铂双金属纳米颗粒(NPs),并将其用作抗癌药物阿霉素(DOX)的递送载体。用硫醇功能化透明质酸(HA-SH)对DOX@PdPt NPs进行修饰,以生成平均尺寸为105.2±6.7 nm的DOX@PdPt@HA NPs。进一步对DOX@PdPt@HA NPs进行表征以及体内和体外抗肿瘤效果评估。制备的DOX@PdPt@HA NPs在单个808 nm近红外(NIR)激光照射下呈现出49.1%的高光热转换效率。此外,NIR激光照射诱导的光热效应触发了DOX从DOX@PdPt@HA NPs中的释放。在体外,近红外照射的DOX@PdPt@HA NPs的联合化疗-光热治疗对小鼠乳腺癌4T1细胞的细胞活力的抑制作用比DOX或近红外照射的PdPt@HA NPs更强。此外,在通过皮下接种4T1细胞建立的小鼠肿瘤模型中使用近红外照射的DOX@PdPt@HA NPs进行的体内联合治疗,与单独的化疗或光热治疗相比,显示出显著的肿瘤生长抑制作用。半胱天冬酶-3和Ki-67的免疫组织化学染色结果表明,肿瘤细胞凋亡增加和增殖减少有助于化疗-光热治疗的抗肿瘤作用。此外,DOX@PdPt@HA NPs在体内诱导的毒性可忽略不计。因此,所开发的纳米平台在光热治疗、药物递送和控释方面具有巨大的应用潜力。