Combined chemotherapy based on bioactive black phosphorus for pancreatic cancer therapy.
Combined chemotherapy based on bioactive black phosphorus for pancreatic cancer therapy.
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DOI：
10.1016/j.jconrel.2022.12.054
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Shengyong Geng;Xianbin Zhang;Tingting Luo;Min Jiang;Chenchen Chu;Lie Wu;P. Gong;Wenhua Zhou
中科院分区：
文献类型：
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作者：
Shengyong Geng;Xianbin Zhang;Tingting Luo;Min Jiang;Chenchen Chu;Lie Wu;P. Gong;Wenhua Zhou
胰腺癌是最具侵袭性的恶性肿瘤，早期诊断困难，晚期生存期短，缺乏有效的治疗方案。在这项工作中，一种新的联合化疗策略的基础上，生物活性黑磷（BP）和吉西他滨（GEM）的有效治疗胰腺癌。联合应用BP和GEM对胰腺癌细胞的G 0/G1期阻滞和G2/M期阻滞，可协同杀伤胰腺癌细胞，联合指数（CI）< 1。设计并制备了共负载BP量子点（BPQD）和GEM的iRGD修饰的玉米醇溶蛋白纳米颗粒作为靶向纳米平台（BP-GEM@NPs）。静脉注射后，体内分布和药代动力学结果表明BP-GEM@NPs具有出色的肿瘤靶向能力，并显着延长血液循环时间。BPQD和GEM的靶向共递送在皮下异种移植物和原位模型中诱导更多的胰腺肿瘤细胞凋亡并协同抑制肿瘤生长。同时，BP-GEM@NPs具有良好的生物相容性，无不良反应。这项工作表明了BP-GEM@NPs作为胰腺癌联合化疗的巨大潜力，并通过探索纳米材料的内在生物活性为生物医学的发展提供了见解。
Pancreatic cancer is the most aggressive malignant tumor with difficulty in early diagnosis, very short survival time in advanced stage, and lack of effective treatment options. In this work, a novel combination chemotherapy strategy based on bioactive black phosphorus (BP) and gemcitabine (GEM) is developed for efficient treatment of pancreatic cancer. The combined cell cycle blockage in G2/M phase induced by BP and G0/G1 phase by GEM results in synergistic killing of pancreatic cancer cells with the combination index (CI) < 1. The iRGD modified zein nanoparticles co-loaded with BP quantum dots (BPQDs) and GEM are designed and prepared as a targeted nanoplatform (BP-GEM@NPs). After intravenous injection, thein vivodistribution and pharmacokinetics results demonstrate that BP-GEM@NPs shows excellent tumor targeting capability and significantly prolonged blood circulation time. The targeted co-delivery of BPQDs and GEM induces much more pancreatic tumor cell apoptosis and synergistically inhibits tumor growth in both subcutaneous xenograft and orthotopic models. Meanwhile, BP-GEM@NPs exhibit good biocompatibility without bring adverse effects. This work indicates the great potential of BP-GEM@NPs as a combination chemotherapy for pancreatic cancer and provides insights into development of biomedicine by exploring the intrinsic bioactivities of nanomaterials.