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Injectable Biocatalytic Nanocomposite Hydrogel Factories for Focal Enzyme-Prodrug Cancer Therapy
Biomacromolecules ( IF 6.2 ) Pub Date : 2021-09-21 , DOI: 10.1021/acs.biomac.1c00778
Kimika Ono 1 , Hiroyuki Hashimoto 1 , Tokitaka Katayama 1 , Natsumi Ueda 1 , Koji Nagahama 1
Affiliation  

Systemic enzyme-prodrug therapy (EPT) using nanofactories, nanoparticles encapsulating prodrug-activating enzymes, is a promising concept for anticancer therapy. However, systemic delivery systems can be problematic. As nanofactories are typically carried by the blood circulation to tissues throughout the body, conversion of anticancer drugs in normal tissues can cause severe side effects. To overcome this problem, we developed a novel focal EPT approach utilizing nanocomposite hydrogels composed of a poly(dl-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(dl-lactide-co-glycolide) (PLGA–PEG–PLGA) copolymer, LAPONITE, and β-galactosidase (β-gal). The nanocomposite gels can be easily injected locally, and the inherent enzyme activity of β-gal can be preserved long-term. Prodrug 5-FU−β-gal readily permeated into the interior space of gels and was converted into the active anticancer drug 5-FU. Importantly, a single local injection of nanocomposite gels and prodrug 5-FU−β-gal provided long-lasting antitumor activity in vivo without observable side effects, demonstrating the potential utility of injectable biocatalytic hydrogel factories for novel focal EPT systems.

中文翻译:

用于局部酶前药癌症治疗的可注射生物催化纳米复合水凝胶工厂

使用纳米工厂、包裹前药激活酶的纳米颗粒的全身酶前药疗法 (EPT) 是抗癌治疗的一个有前景的概念。然而,全身性递送系统可能存在问题。由于纳米工厂通常由血液循环携带到全身组织,因此在正常组织中转化抗癌药物会导致严重的副作用。为了克服这个问题,我们开发了利用由聚纳米复合水凝胶的新型焦EPT方法(DL -lactide--glycolide) - b -聚(乙二醇) - b -聚(DL -lactide--乙交酯) (PLGA-PEG-PLGA) 共聚物、LAPONITE 和 β-半乳糖苷酶 (β-gal)。纳米复合凝胶可以很容易地局部注射,并且可以长期保留β-gal固有的酶活性。前药 5-FU-β-gal 很容易渗透到凝胶的内部空间并转化为活性抗癌药物 5-FU。重要的是,纳米复合凝胶和前药 5-FU-β-gal 的单次局部注射在体内提供了持久的抗肿瘤活性而没有可观察到的副作用,证明了可注射生物催化水凝胶工厂在新型焦点 EPT 系统中的潜在效用。
更新日期:2021-10-12
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