Cross-linked (R)-(+)-lipoic acid nanoparticles with prodrug loading for synergistic cancer therapy,Journal of Materials Chemistry B

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Cross-linked (R)-(+)-lipoic acid nanoparticles with prodrug loading for synergistic cancer therapy
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-12-16 , DOI: 10.1039/d0tb02425b
Fan Yang _{1,

2,

3,

4} , Yun Chen _{1,

2,

3,

4} , Jing Zhang _{1,

2,

3,

4} , Chunyan Liao _{1,

2,

3,

4} , Shiyong Zhang _{1,

2,

3,

4}

Affiliation

The nonspecific toxicity of loaded drugs and the side effect of carriers are two obstacles that hinder the clinical development of anticancer nanodrugs. Herein, we developed a new nanodrug 3-(methylthio)-propanoate camptothecin (Pro-CPT) loaded with cross-linked (R)-(+)-lipoic acid nanoparticles (Pro-CPT@cLANs). The Pro-CPT is a pH-responsive prodrug of camptothecin (CPT) that can effectively reduce the systemic toxicity of CPT caused by premature release. The cLANs are nanoparticles with structural homology to (R)-(+)-lipoic acid (LA) that hold not only LA-like biocompatibility but also LA-like anticancer activity, which may further relieve the toxicity of loaded drugs by reducing their dosages through synergistic effects and precise drug release at the tumor sites. According to in vitro data, the IC^Pro-CPT₅₀ of Pro-CPT@cLANs against HT29 cells was 0.12 μM, ∼2.5 times lower than that of free Pro-CPT (0.3 μM); in vivo data showed that the tumor inhibition rate (TIR) and survival rate (SR) of Pro-CPT@cLANs against HT29 tumor-bearing nude mice were up to 85.1% and 80%, respectively, also far better than those of free CPT at the same dosage (TIR: 46%, SR: 0%). The Pro-CPT@cLANs provide a simple and efficient strategy to surmount the two obstacles in the development of nanodrugs and hold potential in clinical utility.

中文翻译：

具有前药负载的交联的（R）-（+）-硫辛酸纳米颗粒用于协同癌症治疗

负载药物的非特异性毒性和载体的副作用是阻碍抗癌纳米药物临床开发的两个障碍。在本文中，我们开发了一种新型纳米药物3-（甲硫基）-丙酸喜树碱（Pro-CPT），其上载有交联的（R）-（+）-硫辛酸纳米颗粒（Pro-CPT @ cLANs）。Pro-CPT是喜树碱（CPT）的一种pH响应型前药，可有效降低因过早释放而引起的CPT全身毒性。cLANs是与（R）-（+）-硫辛酸（LA）具有结构同源性的纳米颗粒，不仅具有类似LA的生物相容性，而且具有类似LA的抗癌活性，可通过降低其剂量进一步减轻所装载药物的毒性通过协同作用和精确的药物释放在肿瘤部位。根据体外数据显示，Pro-CPT @ cLANs对HT29细胞的IC ^Pro-CPT₅₀为0.12μM，比游离Pro-CPT（0.3μM）低约2.5倍；体内数据显示Pro-CPT @ cLANs对HT29荷瘤裸鼠的抑瘤率（TIR）和存活率（SR）分别高达85.1％和80％，也远好于游离CPT在相同剂量下（TIR：46％，SR：0％）。Pro-CPT @ cLANs提供了一种简单有效的策略来克服纳米药物开发中的两个障碍，并在临床应用中具有潜力。

更新日期：2021-01-20

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