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基于具有高载药量的大孔冷冻凝胶的按需宏观递送系统用于增强癌症治疗

On-Demand Macroscale Delivery System Based on a Macroporous Cryogel with a High Drug Loading Capacity for Enhanced Cancer Therapy.

作者信息

Im Pilseon, Kim Jaeyun

出版信息

ACS Biomater Sci Eng. 2018 Oct 8;4(10):3498-3505. doi: 10.1021/acsbiomaterials.8b00911. Epub 2018 Sep 24.

DOI:10.1021/acsbiomaterials.8b00911
PMID:33450796
Abstract

The macroscale delivery system has been one of the practical platforms for a controlled delivery system by acting as a local depot close to the target tissue. In this study, we fabricated a macroporous alginate crygel incorporated with gold nanorods (GNRs) for the on-demand release of a chemotherapeutic drug from macroscale materials placed beside the target tumor. The macroporous crygel was prepared by the ice-crystal templating of a covalently crosslinked alginate hydrogel incorporated with GNRs. Mitoxantrone (MX), one of the potent anticancer drugs with a positive charge, was strongly adsorbed on the negative alginate chains of the cryogels. This system enabled a high loading of MX and a successful on-demand release of strongly bound MX from the GNR-loaded macroporous cryogels by near-infrared (NIR) irradiation by the dissociation of the interaction between the alginate backbone and MX. Cell viability after the NIR irradiation of the MX-loaded macroporous cryogel was significantly lower compared to that under no stimuli conditions. The in vivo test showed that repetitive NIR irradiations on the MX-loaded cryogel implanted near the tumor suppressed the tumor volume six times more than that of the control group. This simple approach to fabricate a macroporous cryogel capable of the on-demand release of bioactive cargos could be beneficial in various applications including cell, gene, and the other small molecule delivery systems.

摘要

宏观递送系统通过作为靠近靶组织的局部储存库,一直是可控递送系统的实用平台之一。在本研究中,我们制备了一种掺入金纳米棒(GNRs)的大孔海藻酸盐冷冻凝胶,用于从置于靶肿瘤旁边的宏观材料中按需释放化疗药物。大孔冷冻凝胶是通过对掺入GNRs的共价交联海藻酸盐水凝胶进行冰晶模板化制备的。米托蒽醌(MX)是一种带正电荷的强效抗癌药物,它强烈吸附在冷冻凝胶的负电荷海藻酸链上。该系统能够实现MX的高负载,并通过近红外(NIR)照射使负载GNRs的大孔冷冻凝胶中强结合的MX通过海藻酸主链与MX之间相互作用的解离而成功按需释放。与无刺激条件下相比,负载MX的大孔冷冻凝胶经近红外照射后的细胞活力显著降低。体内试验表明,对植入肿瘤附近的负载MX的冷冻凝胶进行重复近红外照射,其肿瘤体积的抑制程度比对照组高六倍。这种制备能够按需释放生物活性物质的大孔冷冻凝胶的简单方法,在包括细胞、基因和其他小分子递送系统在内的各种应用中可能是有益的。

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