Nanoparticles for Multimodal Antivascular Therapeutics: Dual Drug Release, Photothermal and Photodynamic Therapy

TL;DR

This study develops a tumor blood vessel-targeted nanoparticle capable of dual drug delivery and multimodal therapy, including photothermal and photodynamic effects, showing promising anti-vascular results in a cancer model.

Contribution

It introduces a novel RGD-targeted nanoparticle that co-delivers two anti-vascular drugs and combines multiple therapeutic modalities activated by Near-Infrared light.

Findings

Enhanced uptake by HUVEC cells with RGD targeting

Effective killing of endothelial cells upon NIR irradiation

Significant reduction of tumor blood vessels in vivo

Abstract

The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-targeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels upon irradiation. These results suggest that the combination of different anti-vascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future.