Temozolomide encapsulated and folic acid decorated chitosan nanoparticles for lung tumor targeting: improving therapeutic efficacy both in vitro and in vivo

被引：18

作者：

Li, Kaidi ^{[1
,2
]}

Liang, Naixin ^{[1
,2
]}

Yang, Huaxia ^{[2
,3
]}

Liu, Hongsheng ^{[1
,2
]}

Li, Shanqing ^{[1
,2
]}

机构：

[1] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Thorac Surg, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci, Beijing 100730, Peoples R China

[3] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol, Beijing 100730, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 67期

关键词：

temozolomide; chitosan; lung cancer; non-small-cell lung cancer; targeted drug delivery; DRUG-DELIVERY; FOLATE; CYTOTOXICITY; NANOCAPSULES; CARRIERS;

D O I：

10.18632/oncotarget.22791

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Folic acid-conjugated temozolomide (TMZ)-loaded chitosan nanoparticles (CS-TMZ-FLA-NP) were developed to target lung cancer in the anticipation that folic acid would increase the affinity of nanoparticles for cancer cells. CS-TMZ-FLA-NP showed the highest anti-proliferative effect on the lung cancer cells in comparison to free TMZ and CS-TMZ-NP (nanoparticles without folic acid). A cellular uptake assay was performed on two different cell lines, L132 and A549. Cellular uptake efficiencies of CS-TMZ-NP and CS-TMZ-FLA-NP were found to be concentration-dependent in both cell lines. CS-TMZ-FLA-NP produced a 2.5 fold greater accumulation of TMZ than CS-TMZ-NP in both cell lines. CS-TMZ-FLA-NP maintained a significantly higher deposition of TMZ in lung tissue (approximately 7.5 mu g/g of lung tissue) when compared to free TMZ and CS-TMZ-NP. Mice treated with CS-TMZ-FLA-NP had a 100% survival rate with significant suppression of tumor growth. Histopathological and immunohistochemical studies also demonstrated that CS-TMZ-FLA-NP had superior anticancer activity compared to the other two treatments. Our results indicate that CS-TMZ-FLA-NP can effectively facilitate targeting to human lung cancer cell lines in vitro and to lung tumors in vivo in a sustained manner and so improve the therapeutic efficacy of TMZ.

引用

页码：111318 / 111332

页数：15

共 43 条

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