MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 310027, P. R. China.
Biomater Sci. 2021 Jul 7;9(13):4737-4745. doi: 10.1039/d1bm00520k. Epub 2021 May 25.
The current trend in tumor research is shifting from monotherapy to multimodal therapy. However, how to achieve on-demand drug delivery and minimize the invasiveness of treatment are still big challenges. Herein, we present a detachable microneedles (MNs) system, which consists of polycaprolactone (PCL) needles and polyvinylpyrrolidone/poly (vinyl alcohol) substrate, to build an implanted drug depot for on-demand photothermo-chemotherapy. Owing to the dissolvability of the substrate, detachable MNs can intradermally implant PCL needles loaded with photothermal conversion agent Prussian blue nanocubes (PB NCs) and chemotherapeutics doxorubicin hydrochloride (Dox·HCl). Once near-infrared light irradiates, PB NCs could translate light to local regional hyperthermia, which not only ablates cancer cells but also meltPCL to accelerate the diffusion of Dox·HCl. These MNs displayed a stable and repeatable photothermal effect under NIR irradiation. The ex vivo experiments using isolated swine skin demonstrated the as needed Dox·HCl delivery triggered by NIR light. Moreover, the robust antitumor efficacy of the MN system was proved in KB tumor-bearing nude mice under three timed NIR irradiation. Therefore, the developed detachable MNs which could build implanted "arsenal" for on-demand photothermo-chemotherapy have a bright future in tumor suppression.
目前,肿瘤研究的趋势正从单一疗法向多模式疗法转变。然而,如何实现按需药物输送并最小化治疗的侵入性仍然是巨大的挑战。在这里,我们提出了一种可分离的微针(MNs)系统,它由聚己内酯(PCL)针和聚乙烯吡咯烷酮/聚乙烯醇(PVP/PVA)基底组成,用于构建按需光热化学治疗的植入式药物库。由于基底的可溶解性,可分离的 MNs 可以将负载光热转换剂普鲁士蓝纳米立方(PB NCs)和化疗药物盐酸阿霉素(Dox·HCl)的 PCL 针皮内植入。一旦近红外光照射,PB NCs 可以将光转化为局部区域的过热,不仅可以杀死癌细胞,还可以融化 PCL 以加速 Dox·HCl 的扩散。这些 MNs 在近红外光照射下表现出稳定且可重复的光热效应。使用分离的猪皮进行的离体实验证明了近红外光触发的按需 Dox·HCl 输送。此外,在 KB 荷瘤裸鼠中,通过三次定时近红外光照射,证实了 MN 系统强大的抗肿瘤疗效。因此,开发的可分离 MNs 可以为按需光热化学治疗构建植入式“武器库”,在肿瘤抑制方面具有广阔的前景。