RESUMO
A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells.
Assuntos
Antibióticos Antineoplásicos/química , Biotina/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Grafite/química , Pontos Quânticos/química , Células A549 , Antibióticos Antineoplásicos/administração & dosagem , Biotina/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Grafite/administração & dosagem , Humanos , Nanotubos de Carbono/química , Neoplasias/metabolismo , Pontos Quânticos/administração & dosagemRESUMO
Two pH and temperature controlled drug delivery systems for cancer therapy are here reported by using vapour phase and liquid phase functionalized multiwalled carbon nanotubes (MWCNT). Both oxidized MWCNT were functionalized at the carboxyl groups with a short hydrophilic polyethylene glycol (PEG) chain. The nanosystems were loaded with doxorubicin and covered with the biocompatible polymer polylactide, able to form hydrogen bonding with PEG and to entrape the drug inside the two polymeric chains. The different oxidative reaction conditions of MWCNT have demonstrated to deeply affect their agglomeration ability and the available reactive surface area for drug loading which in turn, affected the drug release abilities of the synthesized polymer-gated drug delivery systems. The in vitro release abilities as well as their antiproliferative effect on three different human cancer cell lines were evaluated and compared, highlighting the possibility to tune the amount of drug released by controlling the functionalization degree of the carbon nanotube based material. Biological tests highlighted the high biocompatibility of both systems and their ability to deliver doxorubicin to cancer cells.