Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime
- Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime
- 최기영; V. G. Deepagan; 고혜원; 권승리; N. Vijayakameswara Rao; 김상균; 엄우람; 이소희; 민지웅; 이정진; 신솔; 서민아; 박재형
- Issue Date
- Nano letters
- VOL 18, NO 4-2644
- 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.
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