Injectable and Quadruple-Functional Hydrogel as an Alternative to Intravenous Delivery for Enhanced Tumor Targeting

Authors
Zhang, Zhi-QiangKim, Young-MinSong, Soo-Chang
Issue Date
2019-09-25
Publisher
American Chemical Society
Citation
ACS Applied Materials & Interfaces, v.11, no.38, pp.34634 - 34644
Abstract
Intravenous (IV) route is the most commonly used drug-delivery approach. However, the targeting efficiency to tumor through IV delivery is usually less than 10%. To address this limitation, we report a new systemic delivery method utilizing injectable and quadruple-functional hydrogels to improve targeting efficiency through passive, active, and magnetic targeting, and hydrogel-controlled sustained release. The hydrogels consist of a folate/polyethylenimine-conjugated poly(organophosphazene) polymer, which encapsulates small interfering RNA (siRNA) and Au-Fe3O4 nano-particles to form a nanocapsule (NC) structure by a simple mixing. The hydrogels are localized as a long-term "drug-release depot" after a single subcutaneous injection and sol-gel phase transition. NCs released from the hydrogels enter the circulatory systems and then target the tumor through enhanced permeability and retention/folate/magnetism triple-targeting, over the course of circulation, itself prolonged by the controlled release. In vivo experiments show that 12% of NCs are successfully delivered to the tumor, which is a considerable improvement compared to most results through IV delivery. The sustained targeting of gold to tumor enables two cycles of photothermal therapy, resulting in an enhanced silencing effect of siRNA and considerable reduction of tumor volume, which we are unable to achieve via simple intravenous injection.
Keywords
SIRNA DELIVERY; LONG-TERM; IN-VIVO; NANOPARTICLES; OXIDE; GENE; SENSITIVITY; EFFICIENT; SIRNA DELIVERY; LONG-TERM; IN-VIVO; NANOPARTICLES; OXIDE; GENE; SENSITIVITY; EFFICIENT; quadruple-functional hydrogel; alternative to IV; triple-targeting; sustained release; long-term therapy
ISSN
1944-8244
URI
https://pubs.kist.re.kr/handle/201004/119557
DOI
10.1021/acsami.9b10182
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KIST Article > 2019
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