Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice

被引:160
作者
Lee, So Jin [1 ,2 ]
Park, Kyeongsoon [1 ]
Oh, Yu-Kyoung [2 ]
Kwon, Seung-Hae [3 ]
Her, Songwook [3 ]
Kim, In-San [4 ]
Choi, Kuiwon [1 ]
Lee, Sung Jun [5 ]
Kim, Hoyoung [5 ]
Lee, Se Geun [5 ]
Kim, Kwangmeyung [1 ]
Kwon, Ick Chan [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Biomed Res Ctr, Seoul 136791, South Korea
[2] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136713, South Korea
[3] Korea Basic Sci Inst, Chuncheon Ctr, Div Analyt Bioimaging, Chunchon 200701, Gangwon Do, South Korea
[4] Kyungpook Natl Univ, Taegu 700422, South Korea
[5] Daegu Gyeongbuk Inst Sci & Technol, Adv Nano Mat Res Team, Dept Nano Technol, Taegu 704230, South Korea
关键词
Chitosan-based nanoparticles; Photosensitizer; Drug delivery system; Tumor target specificity; Photodynamic therapy; SELF-ASSEMBLED NANOPARTICLES; PHOTODYNAMIC THERAPY; CARRIERS;
D O I
10.1016/j.biomaterials.2009.01.058
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
We reported the development of new nanoscale drug carriers, chitosan-based nanoparticles (CNPs) that can be used for photodynamic therapy. These carriers could encapsulate a photosensitizer, protophorphyrin IX (PpIX), and deliver it to tumor tissue. We already reported that CNPs presented the enhanced tumor target specificity in cancer therapy and imbibed various water insoluble anticancer agents into the hydrophobic multicores of nanoscale particles. In this study, we prepared photosensitizer-encapsulated CNPs by self-assembling amphiphilic glycol chitosan-5 beta-cholanic acid conjugates in an aqueous environment and then encapsulating the water-insoluble photosensitizer (PpIX), with high drug-loading efficiency (>90%) by using a dialysis method. Freshly prepared PpIX-encapsulated CNPs (PpIX-CNPs) had an average diameter of 290 nm and were stable in aqueous solutions for 1 month. As nanoscale drug carriers, PpIX-CNPs exhibited a sustained release profile in vitro and were non-toxic to tumor cells in the dark. In a cell culture system, we observed rapid cellular uptake of the PpIX-CNPs and the released PpIX from CNPs became highly phototoxic upon visible irradiation. In SCC7 tumor-bearing mice, PpIX-CNPs exhibited enhanced tumor specificity and increased therapeutic efficacy compared to free PpIX. Taken together, our results indicate that PpIX-CNPs have potential as an effective drug delivery system for clinical photodynamic therapy. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2929 / 2939
页数:11
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