DNA Nanostructures as Pt(IV) Prodrug Delivery Systems to Combat Chemoresistance

Cisplatin is a first‐line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem...

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Published inSmall (Weinheim an der Bergstrasse, Germany) Vol. 16; no. 38; pp. e2003646 - n/a
Main Authors Zhong, Yi‐Fang, Cheng, Jin, Liu, Yan, Luo, Tao, Wang, Yuqi, Jiang, Kai, Mo, Fangli, Song, Jie
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 01.09.2020
Subjects
Anticancer properties
antitumor activity
Biocompatibility
biodistribution
Cancer
cisplatin resistance
Deoxyribonucleic acid
DNA
DNA nanostructures
Drug delivery systems
In vivo methods and tests
Nanostructure
Nanotechnology
Platinum
Pt(IV) prodrug delivery
Tumors
biodistribution
DNA nanostructures
Pt(IV) prodrug delivery
antitumor activity
cisplatin resistance
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Summary:Cisplatin is a first‐line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these DNA nanostructures could remarkably enhance the cellular internalization of platinum drugs and thus increase the anticancer activity, not only to regular lung cancer cells (A549), but more importantly to cisplatin‐resistant cancer cells (A549cisR). Further, in vivo studies also demonstrate that cisplatin prodrug loaded DNA nanostructures could effectively suppress tumor growth in both regular and cisplatin‐resistant tumor models. This study suggests that DNA nanostructures are effective carriers for platinum prodrug delivery to combat chemoresistance. Three DNA nanostructures with varied sizes and shapes are constructed and their efficiency as Pt(IV) prodrug delivery systems to combat chemoresistance are investigated. This study has revealed that 6x6x64nt‐Pt(IV), which markedly enhances the cellular internalization of platinum drugs and shows high tumor passive targeting ability, is the optimal design for Pt(IV) prodrug delivery in vitro and in vivo.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202003646