Crystallinity-tuned ultrasoft polymeric DNA networks for controlled release of anticancer drugs

Keonwook Nam, Young Min Kim, Inseok Choi, Hwa Seung Han, Taehyung Kim, Ki Young Choi, Young Hoon Roh

Research output: Contribution to journalArticlepeer-review


Despite the vast interest in utilizing rolling circle amplification (RCA)-based DNA networks for bioapplications, precise control of the mechanical and physicochemical properties is highly challenging. To address this concern, we aimed to develop ultrasoft self-supporting polymerized DNA networks (pDNets) of variable crystallinities to manipulate sequence-mediated drug release efficiency. A controlled ratio of the inorganic magnesium pyrophosphate (MgPPi) crystal to the organic polymeric DNA resulted in the synthesis of pDNets of various nanoporosities. The number of crystal microstructures influencing drug localization and release pattern and the tunable mechanical properties influencing injectability and structural stability under physiological conditions were investigated. The pDNets exhibited ultrasoft properties with Young's moduli of 0.06–0.54 Pa; approximately 9-fold differences in mechanical properties were obtained by varying the degree of crystallinity. With functional DNA sequences, the developed platforms showed pH stimuli-responsive drug release profiles of the dynamic DNA structures and aptamer-specific cell target adhesion efficiency. Analyses of controlled delivery of anticancer therapeutics in vitro and in vivo revealed crystallinity-dependent antitumor efficacy without side effects. This strategy provides an effective one-pot enzymatic polymerization methodology and a favorable microenvironment for a three-dimensional DNA network based on demand-localized drug delivery.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
JournalJournal of Controlled Release
Publication statusPublished - 2023 Mar

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( 2021R1I1A1A01060428 , 2021R1A6A3A13044758 , and 2022R1F1A1073998 ) and the Brain Korea 21 (BK21) FOUR program.

Publisher Copyright:
© 2023 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


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