Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors
- Authors
- Gupta, Biki; Ramasamy, Thiruganesh; Poudel, Bijay Kumar; Pathak, Shiva; Regmi, Shobha; Choi, Ju Yeon; Son, Youlim; Thapa, Raj Kumar; Jeong, Jee-Heon; Kim, Jae Ryong; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh
- Issue Date
- Mar-2017
- Publisher
- AMER CHEMICAL SOC
- Keywords
- metastasis; doxorubicin; imatinib; nanostructured platform; drug delivery; chemoresistance
- Citation
- ACS APPLIED MATERIALS & INTERFACES, v.9, no.11, pp.9280 - 9290
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS APPLIED MATERIALS & INTERFACES
- Volume
- 9
- Number
- 11
- Start Page
- 9280
- End Page
- 9290
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/10078
- DOI
- 10.1021/acsami.6b09163
- ISSN
- 1944-8244
- Abstract
- Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro. DOX/IMT-N significantly inhibited the in vitro proliferation of MDA-MB-231 and SK-MEL-28 cells. The inhibitory effect on in vitro proliferation of the cells was significantly greater than the effect of free DOX, DOX/IMT cocktail, or the nanostructured system housing DOX only (DOX-N). DOX/IMT-N remarkably enhanced cellular drug uptake, resulting in enhanced apoptosis, caused by significant increases in the expression levels of apoptotic marker proteins. Intravenous administration of DOX/IMT-N to MBA-MB-231 xenograft tumor-bearing mice resulted in significantly improved inhibition of tumor progression compared to that with DOX, DOX/IMT, or DOX-N. Therefore, the nanostructured DOX/IMT-N system could potentially aid in overcoming drug resistance in metastatic tumors and improve the effectiveness of metastatic tumor therapeutics.
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