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POSTECH, 기초과학연구원

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Biomaterials, Volume 217, October 2019, 119297 | https://doi.org/10.1016/j.biomaterials.2019.119297 Tumor vasodilation by N-Heterocyclic carbene-based nitric oxide delivery triggered by high-intensity focused ultrasound and enhanced drug homing to tumor sites for anti-cancer therapy

Youngnam Kang^a,1, Jeesu Kim^d,1, Junbeom Park^b,c, Yeong Mi Lee^c, Gurusamy Saravanakumar^c, Kyeng Min Park^b, Wonseok Choi^d, Kimoon Kim^b,c, Eunsung Lee^b,c, Chulhong Kim^d, Won Jong Kim^a,c

^aSchool of Interdisciplinary Bioscience and Bioengineering, POSTECH (Pohang University of Science and Technology), Pohang 37673, Republic of Korea
^b Center for Self-Assembly and Complexity (CSC), Institute for Basic Science (IBS), Pohang 37673, Republic of Korea
^c Department of Chemistry, POSTECH (Pohang University of Science and Technology), Pohang 37673, Republic of Korea
^dDepartment of Creative IT Engineering and Electrical Engineering, POSTECH (Pohang University of Science and Technology), Pohang 37673, Republic of Korea

^*Corresponding authors

¹These authors contributed equally on this work.

Abstract

Nitric oxide (NO) is widely known as an effective vasodilator at low concentrations. Drug delivery systems combined with NO can dilate blood vessels surrounding tumor tissues, and the drug accumulation in tumors is accelerated by the enhanced permeability and retention effect, leading to an improvement in the anti-tumor effect. N-heterocyclic carbene-based NO donors (e.g., 1,3-bis-(2,4,6-trimethylphenyl)imidazolylidene nitric oxide (IMesNO) have been developed for stable NO storing in air and water, and NO release by thermolysis. Herein, we demonstrated on-demand NO release by high-intensity focused ultrasound (HIFU) as a stimulus, which generated high heat and exerted an ablation effect when treated in vivo. We demonstrated IMesNO to be a HIFU-responsive NO donor and its potential application in vivo using IMesNO-loaded micelles. Moreover, IMesNO-loaded micelles mixed with drug-loaded micelles (IMesNO/DOX@MCs) showed acceleration of drug accumulation in tumor sites and enhanced tumor growth inhibition. Thus, our findings suggest a potential clinical bioapplication of NO-releasing drug-loaded micelles owing to the therapeutic function of NO and HIFU treatment for anti-cancer therapy.

Keywords : N-heterocyclic carbenes; Nitric oxide delivery; High-intensity focused ultrasound; Vasodilation; On-demand therapy

논문정보

형식Research article
게재일2019년 10월 (BRIC 등록일 2019-07-09)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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