Smart Dual-Functionalized Gold Nanoclusters for Spatio-Temporally Controlled Delivery of Combined Chemo- and Photodynamic Therapy.

Andrea Tabero,Santi Nonell,Ingrid Nieves,Oriol Planas,Angeles Villanueva,Thibault Gallavardin

doi:10.3390/nano10122474

Abstract

We report the preparation of gold nanoclusters (AuNCs) as a delivery vehicle for the clinically approved photodynamic and chemotherapeutic agents Protoporphyrin IX (PpIX) and doxorubicin (DOX), respectively, and their effect on tumor cells. DOX was attached to the gold nanoclusters through a singlet oxygen-cleavable linker and was therefore released after PpIX irradiation with red light, contributing, synergistically with singlet oxygen, to induce cell death. The doubly functionalized AuNCs proved more effective than a combination of individually functionalized AuNCs. Unlike free DOX, the photoactive nanosystem was non-toxic in the absence of light, which paves the way to introduce a spatiotemporal control of the anticancer therapy and could contribute to reducing the undesirable side effects of DOX.

Highlights

Nanomedicines have become very successful alternatives in very different clinical areas, namely diagnosis, drug delivery, and regenerative medicine [1,2]
We report the preparation of gold nanoclusters (AuNCs) as a delivery vehicle for the clinically approved photodynamic and chemotherapeutic agents Protoporphyrin IX (PpIX) and doxorubicin (DOX), respectively, and their effect on tumor cells
We observed a significant increase in PpIX accumulation due to its attachment to AuNCs (Figure 5a)

Summary

Introduction

Nanomedicines have become very successful alternatives in very different clinical areas, namely diagnosis (nanodiagnosis), drug delivery (nanotherapy), and regenerative medicine [1,2]. The most important advantage of nanoparticles as drug delivery systems is the co-delivery of multiple therapeutic agents on the same platform which allows a spatio-temporal controlled release of attached drugs [4,5]. Out of this innovative approach emerged the concept of photonanomedicine, which develops light-activable nanosystems that integrate therapeutics and diagnostics (theranostics), selection of the molecular agents and perfect control of the time, the place and the dosage when releasing therapeutic agents [3]. Photonanomedicine is based on the conjunction of nanotechnology and photodynamic therapy (PDT)

Methods

Results

Conclusion