UCST型载药胶束/纳米纤维复合膜对癌细胞沿腹膜扩散的抑制机制研究

研究显示多种癌症术后残留癌细胞较易沿腹膜扩散，如何抑制此类扩散成为预防癌症复发的关键之一。静电纺丝法制备的药物载体已被广泛应用于抗癌药物缓控释领域，但如何实现药物载体在术后创口部位长时间锚定且开关式释放的研究尚无相关报道。本项目旨在利用同轴静电纺丝法制备以水溶性聚合物（负载UCST型温敏载药胶束和银纳米粒子）为芯层，以疏水型聚合物为壳层的纳米纤维复合膜。通过近红外光周期性辐照术后植入腹腔内的复合膜，周期性辐照银纳米粒子导致的升温能诱导锚定在复合膜内UCST型胶束开关式释放所载药物，锚定在术后创口部位的复合膜和超长的药物释放周期能抑制癌细胞沿腹膜的扩散。系统研究同轴纤维复合膜的形貌和结构等对药物开关式释放性能的影响规律，重点考察纤维复合膜对近红外光响应的灵敏性及对术后残留癌细胞沿腹膜扩散的抑制效果。本项目的研究成果可为术后残留癌细胞沿腹膜扩散的有效抑制提供新的思路。

Sevaral residual cancer cells prefer to proliferate along peritoneum after cancer resection, how to restrain such proliferation has become one of the key point to prevent recurrence of cancers. Drug carriers by electrospinning has been widely used in the field of controlled drug release. However, relevant literatures haven’t reported yet about how to immobilize the carriers in the postoperative wound site and keep them switchable release. Herein, the proposal focuses to prepare nanofiber composite membranes via coaxial electrospinning with water-soluble polymer (UCST-Type micelles and silver nanoparticles loaded ) as the core and hydrophobic polymer as shell. Immobilized UCST-Type micelle in the composite membranes show switchable drug release due to increased temperature, which induced by periodic near-infrared light irradiation on composite membrane containing silver nanparticles implanted inside peritoneum after cancer resection. Thus the immobilized composite membrane in postoperative wound site can inhibit the proliferation of residual cancer cells along the peritoneum and realized long-term of drug release. The effects of the morphology and structure of the coaxial fibrous composite membranes on the drug release performance will be investigated systematically. The sensitivity of fiber composite membrane response to near infrared light and the inhibition efficiency on cancer cells proliferation will be investigated. The achievements of this proposal will provide a new insight into effectively restrain proliferation along peritoneum after cancer resection.