Paclitaxel-loaded hollow-poly（4-vinylpyridine） nano- particles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs,...

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Published in纳米研究：英文版 Vol. 10; no. 3; pp. 856 - 875
Main Author Rafael Contreras-Caceres Maria C. Leiva Raul Ortiz Amelia Diaz Gloria Perazzoli Miguel A.Casado-Rodriguez Consolacion Melguizo Jose M. Baeyens Juan M. Lopez-Romero Jose Prados
Format Journal Article
LanguageEnglish
Published 2017
Subjects
4-乙烯基吡啶
中空
乳腺癌
治疗药物
紫杉醇
纳米颗粒增强
细胞株
肺癌
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Summary:Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.
Bibliography:Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.
paclitaxel,poly（4-vinylpyridine）（p4VP） nanoparticles,lung cancer,breast cancer,cytotoxicity,multicellular tumorspheroids
11-5974/O4
ISSN:1998-0124
1998-0000