Abstract

In the photothermal treatments (PTs) of tumor, the localization of a high number of near-infrared (NIR) absorbing gold nanoparticles in the tumor mass is still a challenging issue. Here, we propose a promising strategy to deliver therapeutic chitosan-coated gold nanoparticles to tumor cells as hidden cargo of Endothelial Colony Forming Cells (ECFCs) endowed with an innate tumor-tropism. Remarkably, ECFC gold enrichement doesn't affect cell viability and preserves the endothelial lineage characteristics such as capillary morphogenesis and cell migration. We demonstrate that heavily Au-doped ECFCs are able to efficiently warm up the tumor environment, and kill the cancer cells via hyperthermic heating both in vitro as well as in vivo. Thus, we show an excellent thermotransductive property of gold enriched ECFCs and their capability to kill melanoma cells at moderate NIR light intensities.

Highlights

  • Cell-based therapies, namely treatments in which stem or progenitor cells are induced to home within damaged or cancer tissues, and nanomaterial-mediated photothermal ablation using near-infrared (NIR) light have significantly advanced and are poised to become a major pillar of modern medicine.In the last decade, cell-mediated delivery has been widely used in the therapy of many kinds of tumors, including glioma, head and neck carcinoma and breast cancer [1, 2]

  • We demonstrate that heavily Au-doped Endothelial Colony Forming Cells (ECFCs) are able to efficiently warm up the tumor environment, and kill the cancer cells via hyperthermic heating both in vitro as well as in vivo

  • We propose alternative NIR-sensitive, tumor tropic cellular vectors, Endothelial Colony Forming Cells (ECFCs), enriched with chitosan-coated Au nanoparticles

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Summary

Introduction

Cell-based therapies, namely treatments in which stem or progenitor cells are induced to home within damaged or cancer tissues, and nanomaterial-mediated photothermal ablation using near-infrared (NIR) light have significantly advanced and are poised to become a major pillar of modern medicine.In the last decade, cell-mediated delivery has been widely used in the therapy of many kinds of tumors, including glioma, head and neck carcinoma and breast cancer [1, 2]. Gold nanoparticles (GNPs) are promising therapeutic tools for the treatment of cancer due to their non-cytotoxic nature, reliable synthesis and functionalization and, most importantly, their tunable plasmonic properties. This allows tailoring gold nanostructures to produce local heating when exposed to near-infrared (NIR) light [5,6,7,8,9]. Virtually all molecular or nanoparticlebased therapies are inaccessible to the hypoxic areas of tumors that lack blood flow, limiting the treatment efficacy [14] It has been reported the effect of PEGylated GNP on deformability and oxygen-delivering ability of the primary functions of erythrocytes [15]. Direct intratumoral injection can be used to circumvent the inefficiency and off-target deposition [16, 17], the injected nanoparticles generally remain at the site of injection and are unable to penetrate the tumor mass leading to incomplete ablation and disease recurrence

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