含有厄洛替尼的中空介孔二氧化硅纳米颗粒的可注射热敏水凝胶作为非小细胞肺癌治疗的局部给药系统,Advanced Science

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含有厄洛替尼的中空介孔二氧化硅纳米颗粒的可注射热敏水凝胶作为非小细胞肺癌治疗的局部给药系统
Advanced Science ( IF 14.3 ) Pub Date : 2020-11-03 , DOI: 10.1002/advs.202001442
Xiaohan Zhou ₁ , Xinlong He ₁ , Kun Shi ₁ , Liping Yuan ₁ , Yun Yang ₁ , Qingya Liu ₁ , Yang Ming ₁ , Cheng Yi ₁ , Zhiyong Qian ₁

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厄洛替尼（ERT），口服制剂，是治疗非小细胞肺癌（NSCLC）最关键的靶向药物之一；然而，其溶解度差、口服生物利用度低和反复无常的毒性限制了更广泛的临床应用。本文基于中空介孔二氧化硅纳米颗粒（HMSN）和热敏聚（d，l-丙交酯）-聚（乙二醇）-聚（d，l-丙交酯）（PDLLA-PEG-PDLLA）制备了一种新型可注射基质、PLEL）水凝胶封装并定位 ERT 的持续释放，以提高针对 NSCLC 的疗效。试管倒置方法表明，这种负载ERT的水凝胶复合材料（ERT@HMSNs/gel）在室温下呈现为可注射的流动溶液，并在生理温度下转变为物理交联的非流动凝胶结构。通过体内成像研究，/凝胶复合材料显示出更长的瘤内和瘤周药物保留。值得注意的是，这种注射给药系统（DDS）在小鼠异种移植模型中提供了抗肿瘤功效和系统安全性之间令人印象深刻的平衡。新型 ERT 负载 HMSN/凝胶系统可能是非小细胞肺癌原位治疗的有希望的候选者。此外，这项研究为设计和制造用于局部抗癌治疗的纳米级输送系统提供了一个前瞻性平台。

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Injectable Thermosensitive Hydrogel Containing Erlotinib‐Loaded Hollow Mesoporous Silica Nanoparticles as a Localized Drug Delivery System for NSCLC Therapy

Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non‐small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l‐lactide)‐poly(ethylene glycol)‐poly(d,l‐lactide) (PDLLA‐PEG‐PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test‐tube‐inversion method shows that this ERT‐loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non‐flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano‐scaled delivery system for localized anticancer therapies.

更新日期：2020-12-03

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