title: Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors.
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.
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Biki
authors.initials: B
authors.lastname: Gupta
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Poudel
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Shiva
authors.initials: S
authors.lastname: Pathak
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Shobha
authors.initials: S
authors.lastname: Regmi
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University , Daegu 705-717, Republic of Korea.
authors.forename: Youlim
authors.initials: Y
authors.lastname: Son
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Thapa
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Jee-Heon
authors.identifier: http://orcid.org/0000-0002-7120-169X
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University , Daegu 705-717, Republic of Korea.
authors.forename: Jae Ryong
authors.initials: JR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University , 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Jong Oh
authors.identifier: http://orcid.org/0000-0002-4929-851X
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D000068877:Imatinib Mesylate; D051379:Mice; D049329:Nanostructures
chemical_list: D004317:Doxorubicin; D000068877:Imatinib Mesylate
keywords: chemoresistance; doxorubicin; drug delivery; imatinib; metastasis; nanostructured platform