基于静电纺丝纤维毡的精准定位热化疗治疗宫颈癌的实验研究

Cervical cancer is the most common malignant tumor of female reproductive system. Surgical is difficult for locally advanced cervical cancer which is easy to relapse even after radical surgery. Cisplatin is a recognized first-line chemotherapy drug to treat cerical cancer, but often associated with serious side effects by intravenous injection. Polymer-based local drug delivery system is beneficial to drug delivery and controlled release. In our previous work, we prepared cisplatin-loaded polylactic nanofibers by electrospinning technology and orthotopic cervical cancer model in mice. It’s proved that high accumulation of cisplatin in lesion after vaginal implantation of fiber mat, resulting in good safety and efficacy. On the basis of our previous work and tumor comprehensive treatment, we plan to prepare silica nanoparticles co-loaded with cisplatin and indocyanine green, which are subsequently loaded into chitosan nanofibers by electrospining. Orthotopic cervical cancer model in Nude mice will be prepared by using human-derived cervical cancer Hele cells. Near infrared laser through the vaginal cavity is used to induce the thermal effect of indocyanine green nanoparticles. By doing so, precisely localized hyperthermia chemotherapy is expected to be achieved. By study the synergetic effect and safety, we will explore a new way of comprehensive treatment in the treatment of cervical cancer, laying the foundation for future clinical application.

宫颈癌是最常见的女性生殖系统恶性肿瘤，主要临床问题是晚期局部宫颈癌手术治疗难度大，根治手术后仍易复发。顺铂是公认的治疗宫颈癌的一线化疗药物，但常规静脉给药的毒副作用较大。高分子材料局部控释给药系统则有利于药物的定位输送和控制释放。前期工作中通过静电纺丝技术制备载有顺铂的聚乳酸纤维毡，运用鼠源u14细胞制备小鼠原位宫颈癌模型，初步证明经阴道植入载药纤维毡后，可实现顺铂在病灶部位的高度蓄集，具有潜在的应用价值。鉴于前期工作基础及传统化疗和热疗的优缺点，本项目拟制备及表征同时载有顺铂和近红外光敏剂吲哚菁绿的二氧化硅纳米粒及载有此纳米粒的壳聚糖纤维毡，运用人源Hele细胞建立裸鼠原位宫颈癌模型，通过阴道腔内近红外激光照射诱发吲哚菁绿的光热效应，从而实现基于静电纺丝纤维毡的精准定位同步热化疗。通过此研究，拟探索一种针对性强的联合治疗宫颈癌的方式，为将来的临床应用打下基础。

局部化疗和热疗很有潜力的联合治疗宫颈癌的方法。在本研究中，我们首先制备了共载有阿霉素和吲哚菁绿的二氧化硅介孔纳米粒。随后运用静电纺丝技术制备了担载此纳米粒的壳聚糖/聚乙烯醇复合纤维毡。模拟阴道环境，验证了载有纳米粒的纤维毡具有优良的精准定位释放药物能力，性能远远优越于载有纳米粒的温敏凝胶。与静脉注射纳米粒相比，通过阴道植入纤维毡可在小鼠阴道达到最大程度的药物蓄积。当纤维毡介导的局部协同热化疗用于治疗小鼠皮下宫颈癌模型的原位宫颈癌模型时，由于结节型肿瘤的肿瘤组织较为致密，药物向肿瘤内部的渗透较为困难。但局部热化疗对原位宫颈癌的抑瘤率仍然高达72.5%，显示了其在宫颈癌治疗领域上的巨大应用潜力。