Zhang Aitang, Li Aihua, Tian Wenxue, Li Zichao, Wei Chen, Sun Yong, Zhao Wei, Liu Mengli, Liu Jingquan
College of Materials Science and Engineering, Institute for Graphene Applied Technology Innovation, Qingdao University, Qingdao, 266071, P. R. China.
School of Pharmacy, Qingdao University, Qingdao, 266021, P. R. China.
Chemistry. 2017 Aug 22;23(47):11346-11356. doi: 10.1002/chem.201701916. Epub 2017 Aug 2.
Molybdenum disulfide (MoS ) nanosheets have attracted significant attention due to their photothermal properties, but the poor solubility and colloidal stability limited their further application in biomedical field. Here, we report a targeted photothermal controllable nanocarrier consisting of MoS nanosheets modified with block copolymer P(OEG-A)-b-P(VBA-co-KH570) and targeting ligand transferrin. P(OEG-A)-b-P(VBA-co-KH570) is synthesized by RAFT polymerization and utilized not only to improve the solubility of MoS nanosheets but also efficiently load the anti-cancer drug doxorubicin (DOX) through an acid-cleavable Schiff base linker. Thiol-functionalized transferrin (Tf-SH) is anchored onto the surface of MoS nanosheets by the formation of disulfide bonds, which could further enhance the cellular uptake of DOX and MoS to HepG2 cells for high-efficiency synergetic therapy. The drug release experiments exhibited the minimal release of DOX at room temperature and neutral pH, and the maximal drug release of 53 % at acidic tumor pH and hyperthermia condition after 48 h. In addition, the DOX-loaded, Tf-SH and P(OEG-A)-b-P(VBA-co-KH570) modified MoS (DOX-POVK-MoS -Tf) showed better a therapeutic effect than DOX-POVK-MoS and POVK-MoS , probably owing to the combined effects of target-directed uptake, acid-triggered drug release, and NIR induced localized heating, which suggest the designed MoS nanocarriers are promising for applications in multi-modal cancer therapy.
二硫化钼（MoS₂）纳米片因其光热性能而备受关注，但较差的溶解性和胶体稳定性限制了它们在生物医学领域的进一步应用。在此，我们报道了一种靶向光热可控纳米载体，它由用嵌段共聚物P(OEG-A)-b-P(VBA-co-KH570)和靶向配体转铁蛋白修饰的MoS₂纳米片组成。P(OEG-A)-b-P(VBA-co-KH570)通过可逆加成-断裂链转移（RAFT）聚合合成，不仅用于提高MoS₂纳米片的溶解性，还通过酸可裂解的席夫碱连接子有效地负载抗癌药物阿霉素（DOX）。硫醇功能化的转铁蛋白（Tf-SH）通过二硫键的形成锚定在MoS₂纳米片表面，这可以进一步增强DOX和MoS₂对HepG2细胞的细胞摄取，以进行高效协同治疗。药物释放实验表明，在室温及中性pH条件下DOX释放量最小，在酸性肿瘤pH和热疗条件下48小时后最大药物释放量为53%。此外，负载DOX、经Tf-SH和P(OEG-A)-b-P(VBA-co-KH570)修饰的MoS₂（DOX-POVK-MoS₂-Tf）显示出比DOX-POVK-MoS₂和POVK-MoS₂更好的治疗效果，这可能归因于靶向摄取、酸触发药物释放和近红外诱导局部加热的联合作用，这表明所设计的MoS₂纳米载体在多模态癌症治疗中具有应用前景。
