Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (01): 69-74.DOI: 10.6023/A12090680 Previous Articles     Next Articles



朱杰, 廖蕾, 朱丽娜, 孔继烈, 刘宝红   

  1. 复旦大学化学系生物医学研究院 聚合物分子工程国家重点实验室 上海 200433
  • 投稿日期:2012-09-18 发布日期:2012-12-20
  • 通讯作者: 刘宝红
  • 基金资助:
    项目受国家自然科学基金(No. 20925517)和长春应用化学研究所电分析化学国家重点实验室(No. SKLEAC201101)资助.

Folate Functionalized Mesoporous Carbon Nanospheres as Nanocarrier for Targetted Delivery and Controlled Release of Doxorubicin to HeLa Cells

Zhu Jie, Liao Lei, Zhu Lina, Kong Jilie, Liu Baohong   

  1. Department of Chemistry, Institute of Biomedical Sciences and State Key Lab of Molecular Engineering of Polymers, Fudan University, Shanghai 200433
  • Received:2012-09-18 Published:2012-12-20
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 20925517) and the State Key Lab of Electroanalytical Chemistry of Changchun Institute of Applied Chemistry (No. SKLEAC201101).

Ordered mesoporous carbon is a kind of novel carrier for intracellular drug release. There are few reports on the use of mesoporous carbon nanospheres (MCNs) as the transmembrane deliverer in human cancer cells; on the other hand, the particle size of MCNs synthesized by hard templates is usually larger than 100 nm. It is accepted that the optimal size of a transmembrane delivery vehicle should be less than 100 nm in diameter and the surface should be hydrophilic to circumvent clearance by macrophages, to maximize circulation times and targeting ability. In this work, MCNs with a diameter of ca. 90 nm have been developed as a targeted drug delivery system of an anticancer drug, doxorubicin (DOX). The small MCNs were synthesized using triblock copolymer Pluronic F127 as a template. The MCNs were first treated by acid to improve its dispersion property in an aqueous solution, and then modified by folic acid through EDC-NHS. The structure of the MCNs was well characterized by transmission electron microscopy, small-angle X-ray scattering, nitrogen adsorption/desorption and dynamic light scattering. pH-dependent drug release is successfully achieved due to the supramolecular π-π stacking between DOX and the carbonaceous structures. By effective passive and active targeting, MCNs can be readily internalized into HeLa cells, where the carried DOX can be efficiently released in the acidic microenvironment of the tumors for further therapy. The results from confocal laser scanning microscope and flow cytometry demonstrated that the cellular uptake efficiency of MCNs toward HeLa cells was increased through the functionalization with folic acid, and the folate modified MCNs show much higher endocytosis properties toward HeLa cells (folate receptor positive) than toward MCF-7 cells (folate receptor negative). The cytotoxicities toward HeLa cells were studied by MTT method, which indicated that the cytotoxicities of DOX loaded mesoporous carbon nanoparticles was also enhanced due to the introduction of folic acid and targeted delivery, while the cytotoxicities of MCNs show very good biocompatibility toward both HeLa and KB cells.

Key words: mesoporous, nanoparticle, cancer, targeted therapy