Yu Yueming, Wang Bingjie, Guo Chunjing, Zhao Feng, Chen Daquan
Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai, 264005, China.
Nanoscale Res Lett. 2019 Sep 18;14(1):316. doi: 10.1186/s11671-019-3138-0.
Laminarin conjugate-based nano-scaled particles were in this study proposed as a delivery system for protoporphyrin IX (Pp IX) in photodynamic therapy (PDT) of human breast cancer cells (MCF-7). Hematin-Laminarin-Dithiodipropionic Acid-MGK, named as HLDM, was an amphiphilic carrier material with dual pH/redox sensitive that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Therefore, we combined photosensitizer (Pp IX) with HLDM to fabricate a novel nano-micelles, herein called Pp IX-loaded HLDM micelles. The Pp IX-loaded HLDM micelles were 149.3 ± 35 nm sized in neutral water. Phototoxicity, in vitro PDT effect, and dual sensibility to pH and redox microenvironment of Pp IX-loaded HLDM micelles were examined at different concentrations by using MCF-7 human breast cancer cells. The experiments on phototoxicity and reactive oxygen species (ROS) production proved that the micelles could produce PDT to kill the cancer cells with a certain wavelength light. The apoptosis experiment indicated that the micelles could cause nuclear damage. In vivo PDT effect of the micelles was studied by constructing the tumor-bearing nude mouse model of MCF-7 cells. In vivo studies showed that the Pp IX-loaded HLDM micelles could induce remarkable anti-tumor effect. A promising laminarin-based nanomedicine platform acts as a new drug delivery system to enhance the uptake, accumulation, and PDT efficacy of Pp IX in vitro and in vivo.
在本研究中,基于海带多糖共轭物的纳米级颗粒被提议作为原卟啉IX(Pp IX)在人乳腺癌细胞(MCF-7)光动力疗法(PDT)中的递送系统。血红素-海带多糖-二硫代二丙酸-MGK,命名为HLDM,是一种具有双重pH/氧化还原敏感性的两亲性载体材料,可用于负载疏水性药物以提高其溶解度并增强生物相容性。因此,我们将光敏剂(Pp IX)与HLDM结合以制备一种新型纳米胶束,在此称为负载Pp IX的HLDM胶束。负载Pp IX的HLDM胶束在中性水中的尺寸为149.3±35 nm。使用MCF-7人乳腺癌细胞在不同浓度下检测了负载Pp IX的HLDM胶束的光毒性、体外PDT效应以及对pH和氧化还原微环境的双重敏感性。光毒性和活性氧(ROS)产生的实验证明,胶束在特定波长的光照射下可产生PDT以杀死癌细胞。凋亡实验表明胶束可导致核损伤。通过构建MCF-7细胞荷瘤裸鼠模型研究了胶束的体内PDT效应。体内研究表明,负载Pp IX的HLDM胶束可诱导显著的抗肿瘤效应。一种有前景的基于海带多糖的纳米药物平台作为一种新型药物递送系统,可在体外和体内增强Pp IX的摄取、积累和PDT疗效。