Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry , Chinese Academy of Sciences , 5625 Renmin Street , Changchun 130022 , P. R. China.
Department of General Surgery , The Second Hospital of Jilin University , 218 Ziqiang Street , Changchun 130041 , P. R. China.
ACS Nano. 2018 Jul 24;12(7):6685-6699. doi: 10.1021/acsnano.8b01729. Epub 2018 Jun 18.
With unsatisfactory effects of systemic chemotherapy for treatment of unresectable or advanced hepatoma, local and sustained delivery of chemotherapeutic agents is becoming a promising solution. The in situ administered platforms increase the drug concentrations in tumor regions, decrease the side effects to organs, prevent the damage to vascular endothelium, and reduce the frequency of drug administration. The prevalent strategy based on minimally invasive transarterial chemoembolization oftentimes induces upper gastrointestinal hemorrhage, liver failure, and liver abscess. In addition, integrating various antitumor drugs in one platform, especially the drugs with different hydrophilic/hydrophobic properties, and achieving sustained and/or sequential release profiles to synergistically inhibit cancer progression remain challenging. In this study, a local drug delivery system made of an emulsion-electrospun polymer patch was developed, which contained hydrophobic 10-hydroxycamptothecin (HCPT) and hydrophilic tea polyphenols (TP) in the shell and core of the nanofiber, respectively. Due to this core-sheath structure, HCPT and TP exhibited sustained and sequential releases first with HCPT followed by TP. HCPT was used to suppress the proliferation and malignant transformation of hepatoma, whereas TP was aimed to decrease the levels of oxygen free radicals and further prevent the invasion and metastasis of tumor cells. Our study presented the potential superiority of this class of core-sheath structured nanofiber membranes in localized treatment of both primary and advanced orthotopic hepatomas.
对于不可切除或晚期肝癌的全身化疗效果不理想，局部和持续输送化疗药物正成为一种有前途的解决方案。原位给药平台增加了肿瘤区域的药物浓度，减少了对器官的副作用，防止了血管内皮的损伤，并减少了药物给药的频率。基于微创经动脉化疗栓塞的流行策略常常会引起上消化道出血、肝功能衰竭和肝脓肿。此外，将各种抗肿瘤药物整合到一个平台中，特别是将具有不同亲水性/疏水性的药物，并实现持续和/或顺序释放曲线以协同抑制癌症进展仍然具有挑战性。在这项研究中，开发了一种由乳液电纺聚合物贴片组成的局部药物递送系统，该系统的外壳和核心中分别含有疏水性 10-羟基喜树碱（HCPT）和亲水性茶多酚（TP）。由于这种核壳结构，HCPT 和 TP 首先以 HCPT 随后以 TP 进行持续和顺序释放。HCPT 用于抑制肝癌的增殖和恶性转化，而 TP 则用于降低氧自由基的水平，进一步防止肿瘤细胞的侵袭和转移。我们的研究表明，这种类核壳结构纳米纤维膜在原发性和晚期原位肝癌的局部治疗中具有潜在的优势。
