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载姜黄素的多重响应性明胶纳米粒的微流体制备及其用于癌症治疗。

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy.

机构信息

School of Pharmacy, Changzhou University, Changzhou 213164, China.

Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, U.K.

出版信息

ACS Biomater Sci Eng. 2023 Jun 12;9(6):3402-3413. doi: 10.1021/acsbiomaterials.3c00318. Epub 2023 May 4.

Abstract

Current anticancer research shows that a combination of multiple treatment methods can greatly improve the killing of tumor cells. Using the latest microfluidic swirl mixer technology, combined with chemotherapy and photothermal-ablation therapy, we developed multiresponsive targeted antitumor nanoparticles (NPs) made of folate-functionalized gelatin NPs under 200 nm in size and with encapsulated CuS NPs, FeO NPs, and curcumin (Cur). By exploring gelatin's structure, adjusting its concentration and pH, and fine-tuning the fluid dynamics in the microfluidic device, the best preparation conditions were obtained for gelatin NPs with an average particle size of 90 ± 7 nm. The comparative targeting of the drug delivery system (DDS) was demonstrated on lung adenocarcinoma A549 cells (low level of folate receptors) and breast adenocarcinoma MCF-7 cells (high level of folate receptors). Folic acid helps achieve targeting and accurate delivery of NPs to the MCF-7 tumor cells. The synergistic photothermal ablation and curcumin's anticancer activity are achieved through infrared light irradiation (980 nm), while FeO is guided with an external magnetic field to target gelatin NPs and accelerate the uptake of drugs, thus efficiently killing tumor cells. The method described in this work is simple, easy to repeat, and has great potential to be scaled up for industrial production and subsequent clinical use.

摘要

当前的抗癌研究表明,多种治疗方法的结合可以极大地提高肿瘤细胞的杀伤率。我们利用最新的微流控旋流混合技术,结合化疗和光热消融治疗,开发出了由叶酸功能化明胶纳米颗粒组成的、大小在 200nm 以下、并包裹了 CuS 纳米颗粒、FeO 纳米颗粒和姜黄素(Cur)的多响应靶向抗肿瘤纳米颗粒(NPs)。通过探索明胶的结构,调整其浓度和 pH 值,并微调微流控装置中的流体动力学,我们获得了最佳的明胶 NPs 制备条件,其平均粒径为 90±7nm。药物传递系统(DDS)的比较靶向性在肺腺癌细胞(A549 细胞,叶酸受体水平低)和乳腺腺癌细胞(MCF-7 细胞,叶酸受体水平高)上得到了证明。叶酸有助于实现 NPs 对 MCF-7 肿瘤细胞的靶向和精确递药。通过红外光照射(980nm)实现了协同光热消融和姜黄素的抗癌活性,而 FeO 则在外磁场的引导下靶向明胶 NPs 并加速药物摄取,从而有效地杀死肿瘤细胞。本工作中描述的方法简单、易于重复,具有很大的潜力可用于工业生产和随后的临床应用。

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