Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes.

Mohamed Wehbe,Malathi Anantha,Marcel Bally,Thititip Tippayamontri,Gabriel Charest,Léon Sanche,Minghan Shi

doi:10.3390/ijms21144848

Abstract

A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier.

Highlights

The necessity to protect healthy tissues surrounding a tumor is a major issue in radiotherapy and limits the therapeutic radiation dose
The preliminary results presented in this paper have allowed investigating the in vitro and in vivo biological response of a wide range of combination of gold nanoparticles (GNPs), X-ray irradiation, carboplatin and a liposomal formulation of carboplatin and GNPs
Mice bearing a human colorectal tumor were treated with radiation alone and in various combination of Pt-chemotherapeutic agent (CA) and GNPs administered by convection-enhanced delivery (CED) [53]

Summary

Introduction

The necessity to protect healthy tissues surrounding a tumor is a major issue in radiotherapy and limits the therapeutic radiation dose. A promising avenue to increase this dose, while decreasing collateral damage consists of developing radiosensitizers or radio-enhancers that increase relative biological effectiveness (RBE) at the tumor [1,2]. In principle, such treatment could be optimized by injecting the radiosensitizer directly into the tumor together with a chemotherapeutic agent. In this case, the detrimental effects of increased radiation dose and chemotherapy would be much more localized at the tumor. The GNPs supply a high density of short-range low energy electrons (LEEs), which strongly and locally react with the Pt-CA bound to vital biomolecules, such as DNA

Methods

Results

Conclusion