Near-Infrared Light Responsive Folate Targeted Gold Nanorods for Combined Photothermal-Chemotherapy of Osteosarcoma

Folate-targeted
gold nanorods (GNRs) are proposed as selective
theranostic agents for osteosarcoma treatment. An amphiphilic polysaccharide
based graft-copolymer (INU-LA-PEG-FA) and an amino derivative of the
α,β-poly­(N-2-hydroxyethyl)-d,l-aspartamide functionalized with folic acid (PHEA-EDA-FA),
have been synthesized to act as coating agents for GNRs. The obtained
polymer-coated GNRs were characterized in terms of size, shape, zeta
potential, chemical composition, and aqueous stability. They protected
the anticancer drug nutlin-3 and were able to deliver it efficiently
in different physiological media. The ability of the proposed systems
to selectively kill tumor cells was tested on U2OS cancer cells expressing
high levels of FRs and compared with human bronchial epithelial cells
(16HBE) and human dermal fibroblasts (HDFa). The property of the nanosystems
of efficiently controlling drug release upon NIR laser irradiation
and of acting as an excellent hyperthermia agent as well as Two Photon
Luminescence imaging contrast agents was demonstrated. The proposed
folate-targeted GNRs have also been tested in terms of chemoterapeutic
and thermoablation efficacy on tridimensional (3-D) osteosarcoma models.