Sorafenib encapsulated in nanocarrier functionalized with glypican-3 specific peptide for targeted therapy of hepatocellular carcinoma
Sorafenib encapsulated in nanocarrier functionalized with glypican-3 specific peptide for targeted therapy of hepatocellular carcinoma
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索拉非尼封装在磷脂酰肌醇蛋白聚糖3特异性肽功能化的纳米载体中用于肝细胞癌的靶向治疗
DOI：
10.1016/j.colsurfb.2019.110498
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发表时间：
2019-12-01
影响因子：
5.8
通讯作者：
Wang, Thomas D.
中科院分区：
文献类型：
--
作者：
Feng, Shuo;Zhou, Juan;Wang, Thomas D.
肝细胞癌（HCC）是世界上第五大常见癌症，发病率不断上升。HCC患者在接受手术切除后需要化疗。严重的脱靶副作用和全身毒性限制了药物的临床应用。靶向治疗纳米药物是提高药物递送效率和减少副作用的创新策略。在这里，我们成功地配制了纳米载体来封装索拉非尼，这是一种FDA批准的用于治疗HCC的药物。索拉非尼被封装，在20天内包封率> 80%。有效水溶性提高了1900倍以上。体外释放率的特征在于半衰期T-1/2 = 22.7 h。肿瘤摄取纳米载体的峰值靶与背景比发生在注射后24小时，并且靶肽与对照相比显著更大。离体生物分布证实了体内结果。治疗21天后，靶肽的肿瘤消退显著大于对照。通过血液化学或尸检未发现急性毒性。总之，已经鉴定出对GPC 3具有特异性的肽，并用于修饰纳米载体的表面，该纳米载体以高包封率包封索拉非尼。HCC异种移植肿瘤的消退显示出靶向药物递送的前景。
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with increasing incidence. Chemotherapy is required for HCC patients after receiving surgical resection. Serious off-target induced side effects and systemic toxicity limit the clinical utility of drugs. Targeting therapeutic nanomedicine is an innovative strategy for enhancing drug delivery efficiency and reducing side effects. Here, we successfully formulated nanocarriers to encapsulate sorafenib, an FDA approved drug for treatment of HCC. Sorafenib is encapsulated with an entrapment efficiency > 80% over 20 days. The effective aqueous solubility is improved over 1900-fold. The release ratio in vitro is characterized by a half-life of T-1/2 = 22.7 h. The peak target-to-background ratio for nanocarrier uptake by tumor occurs at 24 h post-injection, and is significantly greater for the target peptide versus controls. Ex vivo biodistribution confirms the in vivo results. Tumor regression is significantly greater for the target peptide versus controls after 21 days of therapy. No acute toxicity is found by blood chemistry or necropsy. In summary, a peptide specific for GPC3 has been identified, and used to modify the surface of a nanocarrier that encapsulates sorafenib with high entrapment efficiency. Regression of HCC xenograft tumors showed promise for targeted drug delivery.