Block copolymer-templated mineralization for pH-responsive robust nanocarriers of 5-fluorouracil

被引:2
作者
Choi, Gi Hyun [1 ,2 ]
Min, Kyung Hyun [3 ]
Lee, Sang Cheon [1 ,2 ]
机构
[1] Kyung Hee Univ, Sch Dent, Dept Maxillofacial Biomed Engn, Seoul 130701, South Korea
[2] Kyung Hee Univ, Sch Dent, Inst Oral Biol, Seoul 130701, South Korea
[3] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Coll Pharm, Seoul 130701, South Korea
基金
新加坡国家研究基金会;
关键词
mineralization; pH-sensitive; calcium carbonate; 5-fluorouracil; intracellular release; CONTROLLED-RELEASE; TUMOR ACCUMULATION; SIRNA DELIVERY; DRUG-DELIVERY; MICELLES; NANOPARTICLES; DOXORUBICIN; CORE; ENVIRONMENT; SOLUBILITY;
D O I
10.1007/s13233-014-2042-9
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
We describe a novel synthetic method to prepare calcium carbonate (CaCO3)-mineralized nanoparticles for the intracellular delivery of an anticancer drug, 5-fluorouracil (5-FU). The 5-FU-loaded mineralized nanoparticles (FU-CaCO3-MNPs) were prepared by block copolymer (poly(ethylene glycol)-b-poly(L-aspartic acid) (PEG-PAsp))-templated mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO3 (2-)), and negatively charged 5-FU. The mineralization produced hybrid nanoparticles consisting of 5-FU-loaded CaCO3 cores and PEG shells. The mineralized CaCO3 cores of the nanoparticles could stably hold loaded 5-FU by maintaining the structural robustness, and the outer corona of PEG provided colloidal stability to the nanoparticles in serum solutions. The 5-FU release from the FU-CaCO3-MNPs at physiological pH (pH 7.4) was efficiently inhibited, whereas at an endosomal pH (pH 5.0), the 5-FU release was facilitated. Fluorescence microscopic analysis showed that FU-CaCO3-MNPs were taken up by the MCF-7 breast cancer cells, and transferred into acidic endosomes to dissolve the CaCO3 core. Finally, the 5-FU release was facilitated to inhibit the proliferation of cancer cells. These mineralized hybrid nanoparticles may serve as a useful candidate for enhanced intracellular delivery of many ionic anticancer drugs.
引用
收藏
页码:329 / 336
页数:8
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