Simultaneous Cancer Treatment with Photothermal Therapy andChemotherapy using Gold nanorods coated with Methotrexate conjugatedHyaluronic acid

Abstract

Upon near-infrared (NIR) irradiation, combined treatment comprising of photothermal therapy (PTT) and chemotherapy (CHT) offers synergistic effects by inducing localized heat to intended tumor sites and simultaneously allowed delivering drugs thus to minimize undesired side-effects but enhance cytotoxic therapies. In this study we developed a novel platform that enables simultaneously to respond light stimuli with localized heat and released drugs using drug contained gold nanorods (GNRs). Methotrexate (MTX), a model anticancer drug is attached through hydrolytic ester bonding to targeting molecular hyaluronic acid (HA) that is coated onto GNRs. Based on the rationale, HA provides a good scaffold for high biocompatibility to shield risky GNRs, targeting for a CD44 receptor, and easy chemical binding of drugs. Upon a single light irradiation, MTX-HA functionalized GNRs (MTX-HA @GNRs) provide localized heat to cancer areas for PTT and the elevated temperature accelerates hydrolytic cleavage of the ester bond onto GNRs in physiological condition for CHT, ultimately releasing MTX to cells. In contrast to previous combination therapies that do not concurrently offer heat and drugs upon light stimuli, our NIR triggered CHT with PTT provides clinically effective options with combinatorial treatment that possesses high efficacy resulted in in vitro tests. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/719030v1_figsh1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@f215f3org.highwire.dtl.DTLVardef@17f3016org.highwire.dtl.DTLVardef@12e265borg.highwire.dtl.DTLVardef@d85442_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1.C_FLOATNO Schematic illustration of our nanoplatform a) The light responsive combinational therapy using GNRs scaffold for photo thermal therapy and chemotherapy b) The formation of TGNRs@RHO.B-HA and their light responsive mechanism with active CD44 receptor binding affinity c) light triggered hydrolytic release of model drug Rhodamine.B from TGNRs@RHO.B-HA. C_FIG