吴情 肖国岫 徐斌

[摘要]目的：本研究构建了一种新型的牛血清白蛋白纳米药物递送系统，该系统可共递送抗肿瘤药物，用于口腔颌面部腺样囊性癌及其导致的转移性肺癌的治疗。方法：制备的蛋白纳米颗粒负载疏水性化疗药物阿霉素（Dox），并在颗粒表面修饰肿瘤坏死因子相关凋亡诱导配体（TRAIL），以实现靶向共递送治疗性药物，用于治疗转移性肿瘤。结果：本次合成的多功能纳米颗粒具有较好的形貌特征和电位值。体外实验表明，该纳米递送系统具备还原敏感性，在谷胱甘肽（GSH）诱导下能断裂，并释放出Dox，在48h后释放率超过60%。该纳米颗粒不仅可以诱导涎腺腺样囊性癌细胞（SACC-LM）凋亡，还可以有效杀伤A549肺癌细胞，肿瘤细胞对其摄取能力显著增强。由于牛血清白蛋白的生物相容性，纳米颗粒可以在体内长效循环，在聚集到肺部后，有效减少了肺部结节的数量。结论：该纳米系统可以有效递送抗肿瘤药物，具有用于治疗腺样囊性癌的潜力。

[关键词]腺样囊性癌;口腔颌面部;牛血清白蛋白;纳米颗粒;化疗;响应释放

[中图分类号]R782    [文献标志码]A    [文章编号]1008-6455（2021）06-0110-04

Experimental Study of Novel Protein Nanosystems in the Treatment of Adenoid Cystic Carcinoma of Oral and Maxillofacial Region

WU Qing，XIAO Guo-xiu，XU Bin

（Department of Stomatology，Shanghai Fifth People's Hospital，Fudan University，Shanghai 200240，China）

Abstract： Objective  In this study， multifunctional bovine serum albumin nanoparticular delivery system has been developed for the co-delivery of Dox and TRAIL for Adenoid cystic carcinoma therapy. Methods  The nanoparticle was constructed with green synthesis method， which only used conjugation linker （NHS-SS-NHS） without the addition of organic solvent. Results  In the system， Dox was loaded into the synthesized albumin nanoparticle， followed by the modification with TRAIL on the surface. Importantly， the multifunctional nanoparticle was demonstrated to exhibit the reduction-responsive characteristic with over 60% Dox release under the stimulation of GSH within 48h. Besides， both SACC-LM cells and A549 cells could be induced apoptosis， while enhanced internalization of nanoparticle by SACC-LM cells was detected. The in vivo experiments validated the prolonged circulation of this system， which could also significantly decrease the number of metastatic nodules. Conclusion  The novel system could exert excellent antitumor function and exhibited certain potential in clinical application.

Key words： adenoid cystic carcinoma; oral and maxillofacial region; bovine serum albumin; nanoparticles; chemotherapy; reduction-responsive

腫瘤的转移行为是导致死亡率持续增高的重要原因[1]，腺样囊性癌是口腔颌面部常见的恶性肿瘤之一，易转移到肺部，具有较高的致死率[2-3]。对于此类肿瘤的治疗，通常以手术治疗和化疗为主，但效果常常不尽如人意[4]。化疗所用药物难以有效富集到转移肿瘤部位，并且药物体内随机分布所引起的毒副作用也成为死亡率增高的因素[5]。……