Bile acid-conjugated chondroitin sulfate A-based nanoparticles for tumor-targeted anticancer drug delivery |
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| Affiliation: | 1. Universidade de Brasília (UnB) - Campus Planaltina (FUP) – Área Universitária n°01, Vila N. Sa. De Fátima, CEP: 73345–010 – Planaltina, Brasília, DF, Brazil;2. Universidade de Brasília (UnB) - Campus Ceilândia (FCE) - Centro Metropolitano - Conjunto A - Lote 01, CEP: 72220–900 – Ceilândia, Brasília, DF, Brazil;3. Laboratório de Nanobiotecnologia – Instituto de Ciências Biológicas - Universidade de Brasília – UnB - Campus Universitário Darcy Ribeiro - CEP 70910–900 - Asa Norte, Brasília, DF, Brazil;4. Departamento de Química – Universidade Federal de Santa Catarina – CEP: 88040–900 – Trindade, Florianópolis, SC, Brazil;1. College of Pharmacy, Yeungnam University, Gyeongsan 712749, Republic of Korea;2. Department of Pharmaceutics, University of Pharmacy (Yangon), Yangon 11031, Myanmar;3. Department of Pharmaceutical Engineering, Dankook University, Cheonan 31116, Republic of Korea;4. College of Korean Medicine, Haany University, Gyeongsan 712715, Republic of Korea;5. College of Pharmacy, Hanyang University, Ansan 426791, Republic of Korea;1. School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang 332000, China;2. Key Laboratory of Jiangxi Province for Systems Biomedicine, Jiujiang University, Jiujiang 332000, China |
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| Abstract: | Chondroitin sulfate A-deoxycholic acid (CSA-DOCA)-based nanoparticles (NPs) were produced for tumor-targeted delivery of doxorubicin (DOX). The hydrophobic deoxycholic acid (DOCA) derivative was conjugated to the hydrophilic chondroitin sulfate A (CSA) backbone via amide bond formation, and the structure was confirmed by 1H-nuclear magnetic resonance (NMR) analysis. Loading the DOX to the CSA-DOCA NPs resulted in NPs with an approximately 230 nm mean diameter, narrow size distribution, negative zeta potential, and relatively high drug encapsulation efficiency (up to 85%). The release of DOX from the NPs exhibited sustained and pH-dependent release profiles. The cellular uptake of DOX from the CSA-DOCA NPs in CD44 receptor-positive human breast adenocarcinoma MDA-MB-231 cells was reduced when co-treated with free CSA, indicating the interaction between CSA and the CD44 receptor. The lower IC50 value of DOX from the CSA-DOCA NPs compared to the DOX solution was also probably due to this interaction. Moreover, the ability of the developed NPs to target tumors could be inferred from the in vivo and ex vivo near-infrared fluorescence (NIRF) imaging results in the MDA-MB-231 tumor-xenografted mouse model. Both passive and active strategies appear to have contributed to the in vivo tumor targetability of the CSA-DOCA NPs. Therefore, these CSA-DOCA NPs could further be developed into a theranostic nanoplatform for CD44 receptor-positive cancers. |
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| Keywords: | CD44 receptor Chondroitin sulfate A Deoxycholic acid Nanoparticles Tumor targeting |
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