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

Kaidi Li; Naixin Liang; Huaxia Yang; Hongsheng Liu; Shanqing Li

doi:10.18632/oncotarget.22791

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Research Papers:

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

Kaidi Li, Naixin Liang _, Huaxia Yang, Hongsheng Liu and Shanqing Li

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Oncotarget. 2017; 8:111318-111332. https://doi.org/10.18632/oncotarget.22791

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Abstract

Kaidi Li1,*, Naixin Liang1,*, Huaxia Yang2, Hongsheng Liu1 and Shanqing Li1

1Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China

2Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China

*These authors have contributed equally to this work

Correspondence to:

Naixin Liang, email: [email protected]

Keywords: temozolomide; chitosan; lung cancer; non-small-cell lung cancer; targeted drug delivery

Received: August 03, 2017 Accepted: October 28, 2017 Published: November 30, 2017

ABSTRACT

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 μg/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.

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Research Papers:

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

Abstract