Department of Chemistry, Tsinghua University, Beijing 100084, China; Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute (TBSI), The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
Department of Respiratory Diseases, Shenzhen Children's Hospital, 7019 Yitian Road, Futian District, Shenzhen 518026, China.
J Colloid Interface Sci. 2018 Sep 1;525:1-10. doi: 10.1016/j.jcis.2018.04.058. Epub 2018 Apr 16.
Oxaliplatin is a promising antitumor drug, but its effectiveness is limited by its side effects in vivo. In this study, we introduced an Oxaliplatin prodrug (Oxa(IV)) self-controlled release strategy, in which Oxa(IV) is encapsulated by TPGS functionalized mesoporous silica nanoparticles (MSNs), and its release is controlled by biological stimuli, such as acidic environments in tumor tissue and high concentrations of reductants in cancer cells. Despite the lack of auxiliary "gatekeepers" to MSNs, this simplified model of Oxa(IV)-MSNs-TPGS could fine-tune the movements of the drug release. Furthermore, we utilized a prodrug approach to avoid the side effects of Oxaliplatin, and we used TPGS groups to reduce multidrug resistance (MDR). Finally, the toxicity of Oxa(IV)-MSNs-TPGS to a human lung adenocarcinoma cell line (A549) in vitro was significantly lower than that of Oxaliplatin. This model demonstrates the considerable potential of a simple self-controlled release system with multiple functions.
奥沙利铂是一种很有前途的抗肿瘤药物，但由于其体内副作用，其疗效受到限制。在本研究中，我们引入了奥沙利铂前药（Oxa（IV））自控制释放策略，其中 Oxa（IV）被 TPGS 功能化介孔硅纳米粒子（MSNs）包裹，其释放由生物刺激物控制，如肿瘤组织中的酸性环境和癌细胞中的高浓度还原剂。尽管缺乏辅助的“门控”MSNs，但这种简化的 Oxa（IV）-MSNs-TPGS 模型可以微调药物释放的速度。此外，我们利用前药方法来避免奥沙利铂的副作用，并使用 TPGS 基团来减少多药耐药（MDR）。最后，体外实验表明，Oxa（IV）-MSNs-TPGS 对人肺腺癌细胞系（A549）的毒性明显低于奥沙利铂。该模型证明了具有多种功能的简单自控制释放系统具有相当大的潜力。
