Intracellularly Activatable Nanovasodilators to Enhance Passive Cancer Targeting Regime

V. G. Deepagan, Hyewon Ko, Seunglee Kwon, N. Vijayakameswara Rao, Sang Kyoon Kim, Wooram Um, Sohee Lee, Jiwoong Min, Jeongjin Lee, Ki Young Choi, Sol Shin, Minah Suh, Jae Hyung Park

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

Abstract

Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells. After systemic administration of the NO-NPs, we quantitatively assessed and visualized increased tumor blood flow as well as enhanced vascular permeability than could be achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated consequential improvement in therapeutic efficacy over the control groups with considerably improved DOX intratumoral accumulation. Overall, this proof of concept study implies a high potency of the NO-NPs as an EPR enhancer to achieve better clinical outcomes.

Original languageEnglish
Pages (from-to)2637-2644
Number of pages8
JournalNano Letters
Volume18
Issue number4
DOIs
Publication statusPublished - 11 Apr 2018
Externally publishedYes

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