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首页> 外文期刊>RSC Advances >MMP-responsive in situ forming hydrogel loaded with doxorubicin-encapsulated biodegradable micelles for local chemotherapy of oral squamous cell carcinoma
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MMP-responsive in situ forming hydrogel loaded with doxorubicin-encapsulated biodegradable micelles for local chemotherapy of oral squamous cell carcinoma

机译：MMP反应性原位形成的水凝胶载有阿霉素包囊的可生物降解胶束，用于口腔鳞状细胞癌的局部化疗

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The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly( D , L -lactide)-poly(ethylene glycol)-poly( D , L -lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.
机译：口腔内的复杂结构会导致口腔鳞状细胞癌（OSCC）的手术切除不完全，这可能会增加治疗中复发和转移的风险。用微创方法原位形成可注射水凝胶，包封稳定性和刺激性降解已经成为局部药物递送的有希望的载体。在这项研究中，首先将阿霉素（DOX）封装在可生物降解的聚（D，L-丙交酯）-聚（乙二醇）-聚（D，L-丙交酯）（PDLLA-PEG-PDLLA）胶束中，然后将其装入原位注射的透明质酸（HA）水凝胶，通过迈克尔加成反应与基质金属蛋白酶2（MMP-2）响应肽（GCRDGPQGIWGQDRCG）交联。体外研究表明，HA水凝胶具有敏感的MMP-2反应性药物释放曲线。包括MTT，活死，凋亡和伤口愈合试验在内的研究表明，载有DOX胶束的HA水凝胶显示出对鳞状癌细胞（SCC-15）的出色细胞毒性。此外，通过体内研究，我们还证明了HA水凝胶在肿瘤部位的降解速度比正常组织快，这导致局部持续释放DOX的胶束并抑制口腔鳞状细胞癌（OSCC）的肿瘤生长损害器官。因此，这项工作为局部化疗和其他应用提供了卓越的药物递送平台。

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