Implantable fibrous 'patch' enabling preclinical chemo-photothermal tumor therapy
Implantable fibrous 'patch' enabling preclinical chemo-photothermal tumor therapy
复制标题
可植入纤维“补片”实现临床前化学光热肿瘤治疗
DOI：
10.1016/j.colsurfb.2020.111005
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发表时间：
2020-08-01
影响因子：
5.8
通讯作者：
Cai, Xiujun
中科院分区：
文献类型：
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作者：
Cen, Dong;Wan, Zhe;Cai, Xiujun
纤维或水凝胶形式的局部给药系统(LDDS)已经成为有效治疗癌症的一种替代方法，但由于单一的治疗功能而导致的疗效有限，受到了挑战。因此，我们设计并合成了一种多功能LDDS，用于原位化疗-光热协同治疗，显示了微创植入的可行性。在该系统中，多巴胺(PDA)纳米粒子负载阿霉素(DOX)被组装在电纺PCL-明胶(PG@PDA-DOX)纤维的表面。复合的PG@PDA-DOX纳米纤维能够有效地将近红外光转化为热，并表现出良好的光稳定性。此外，低pH和近红外辐射能显著加速DOX的释放。PG@PDA-DOX纤维的体外研究表明，808 nm近红外辐射通过诱导细胞凋亡和抑制细胞增殖而显示出有效的抗癌作用。体内研究表明，通过微创手术将PG@PDA-DOX纳米纤维植入患者来源的异种移植(PDX)模型中，复合纤维可以通过化学-光热联合效应有效地抑制肿瘤生长，而没有明显的全身副作用。因此，这项研究证明了一种纤维网状的微创平台，既具有高疗效，又具有相当大的临床翻译潜力，用于肝癌治疗。
Localized drug delivery systems (LDDSs), in the forms of fibers or hydrogel, have emerged as an alternative approach for effective cancer treatment, but suffer challenges in the limited efficacy originated from sole therapeutic functionality. Herein, a multifunctional LDDS, showing feasibility for minimally-invasive implantation, was designed and synthesized for on-site chemo-photothermal synergistic therapy. In this system, polydopamine (PDA) nanoparticles, loaded with doxorubicin (DOX), were assembled at the surface of electrospun PCL-gelatin (PG) fibers (PG@PDA-DOX). The composite PG@PDA-DOX nanofibers could effectively transform NIR light into heat and present excellent photostability. In addition, low pH and NIR irradiation enabled remarkably accelerated DOX release. The in vitro study of PG@PDA-DOX fibers showed effective anti-cancer effect with irradiation of 808 nm NIR by inducing cell apoptosis and suppressing cell proliferation. The in vivo study, by implanting PG@PDA-DOX nanofibers in the patient derived xenograft (PDX) model via minimally-invasive surgery, presented that the composite fibers can effectively inhabit tumor growth by the combined chemo-photothermal effect without clear systematic side-effects. This study has therefore demonstrated a minimally-invasive platform, in a fibrous mesh form, with both high therapeutic efficacy and considerable potential in clinical translation for liver cancer treatment.