RESUMEN
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,ß-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.
Asunto(s)
Nanotubos , Línea Celular Tumoral , Ácido Fólico , Oro , Humanos , OsteosarcomaRESUMEN
Polymer coated gold nanospheres are proposed as a tumor selective carrier for the anticancer drug doxorubicin. Thiolated polyethyleneglycol (PEG-SH) and an inulin-amino derivative based copolymer (INU-EDA) were used as stabilizing and coating materials for 40 nm gold nanospheres. The resulting polymer coated gold nanospheres (Au@PEG-INU) showed excellent physicochemical stability and potential stealth like behavior. The system was loaded with doxorubicin (Au@PEG-INU/Doxo) and its cytotoxicity profile was evaluated on human cervical cancer cells (HeLa) and lung cancer cells (A549), as compared to Au@PEG-INU and doxorubicin alone. Cytotoxicity assays showed that the system is able to drastically reduce cell viability upon incubation for 3 days. This result was supported by the ability of Au@PEG-INU/Doxo to be internalized by cancer cells and to release doxorubicin, as assessed by fluorescence microscopy. Finally, a cancer/non cancer cell co-culture model was used to display the advantageous therapeutic effects of the proposed system with respect to doxorubicin alone, thereby demonstrating the ability of Au@PEG-INU/Doxo to preferentially accumulate in tumor cells due to their enhanced metabolism, and to selectively kill target cells.
RESUMEN
PURPOSE: An inulin based polycation (Inu-EDA) has been synthesized by the grafting of ethylenediamine molecules onto inulin backbone. The obtained inulin copolymer has been though to coat SPIONs (IC-SPIONs) and obtain stable magnetoplexes by complexation of IC-SPIONs with a model duplexed siRNA, for improving oligonucleotide transfection efficiency. METHODS: The physical-chemical characteristics of IC-SPIONs and IC-SPIONs/siRNA magnetoplexes have been investigated by scanning and transmission electron microscopies, dynamic light scattering, FT-IR and qualitative surface elementary analysis. Cell compatibility and internalization in vitro of IC-SPIONs have been evaluated by MTS and fluorescence microscopy respectively on cancer (HCT116) and normal human (16HBE) cells. The efficiency of gene silencing effect of magnetoplexes was studied on both tumoral (JHH6) and non tumoral (16HBE) cell lines also by applying an external magnet. RESULTS: IC-SPIONs showed dimension of 30 nm and resulted cytocompatible on the tested cell lines; in the presence of an external magnet, the magnetic force enhanced the IC-SPIONs uptake inside cells. Magnetically improved transfection was observed in 16HBE cells under magnetofective conditions, in accordance with the IC-SPIONs uptake enhancement in the presence of an external magnet. CONCLUSIONS: These findings support the potential application of this system as a magnetically targeted drug delivery system. Graphical Abstract Magnetically improved siRNA transfection in cells under magnetofective conditions upon uptake enhancement of IC-SPIONs in the presence of an external magnet.