Sun Luyan, Wan Jiaxun, Schaefer Christian G, Zhang Zihao, Tan Jing, Guo Jia, Wu Limin, Wang Changchun
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, 220 Handan Road, Shanghai, 200433, People's Republic of China.
Department of Materials Science, Fudan University, 220 Handan Road, Shanghai 200433, China.
ACS Biomater Sci Eng. 2017 Mar 13;3(3):381-391. doi: 10.1021/acsbiomaterials.6b00773. Epub 2017 Feb 1.
The rational design of particle-based cancer theranostic agents, combining diagnostic and therapeutic features in a single entity, has emerged as an effective approach toward personalized cancer therapy; however, creating a flexible assembly of specific targeting ligands with regard to a broad range of tumor tissues and cells is still challenging. Here, we present a convenient and highly variable on-site assembly strategy for the preparation of multifunctional doxorubicin (DOX)-loaded nanocargos with magnetic supraparticles (MSPs) as a core and redox-degradable poly(methylacrylic acid-bis(acryloyl) cystamine) (P(MAACy) as the shell, which could be simultaneously modified with multiple targeting ligands through parallelized bioconjugation on the basis of a streptavidin-biotin (SA-BT) interaction. Under physiological conditions similar to those of the cytoplasm of tumor cells, DOX could be released in a controlled manner from these nanocargos to specific tumor sites, while dual-ligand modified nanocargos showed remarkable proliferation inhibition for the HeLa cells and the SK-OV-3 cells that overexpressed both folate as well as integrin receptors. The experimental results demonstrated that the on-site assembly strategy described herein opens access to highly efficient targeting drug delivery systems toward personalized cancer targeting therapy by incorporating functional diversity, which can be easily achieved through highly efficient and parallelized one-step bioconjugation.
基于颗粒的癌症诊疗剂的合理设计，即将诊断和治疗功能结合于一个实体中，已成为个性化癌症治疗的一种有效方法；然而，针对广泛的肿瘤组织和细胞创建特定靶向配体的灵活组装仍然具有挑战性。在此，我们提出了一种便捷且高度可变的原位组装策略，用于制备以磁性超粒子（MSP）为核心、氧化还原可降解的聚（甲基丙烯酸 - 双（丙烯酰基）胱胺）（P(MAACy)）为外壳的负载多柔比星（DOX）的多功能纳米载体，该纳米载体可以基于链霉亲和素 - 生物素（SA - BT）相互作用通过并行生物共轭同时用多种靶向配体进行修饰。在与肿瘤细胞质相似的生理条件下，DOX可以从这些纳米载体以可控方式释放到特定肿瘤部位，而双配体修饰的纳米载体对同时过表达叶酸和整合素受体的HeLa细胞和SK - OV - 3细胞显示出显著的增殖抑制作用。实验结果表明，本文所述的原位组装策略通过纳入功能多样性为个性化癌症靶向治疗开辟了通往高效靶向药物递送系统的途径，这可以通过高效且并行的一步生物共轭轻松实现。
