Evans Blue Derivative Functionalized Gold Nanorods For Photothermal Therapy Enhanced Tumor Chemotherapy

Cancer is a major public health problem worldwide.Most cancer patients are diagnosed at an advanced stage when tumors are surgically unresectable,and thus chemotherapy remains to be only one of the few treatments regimens available.Unfortunately,most traditional chemotherapy drugs are water insoluble and lack tumor targeting capabilities.This results in patient suffering during the treatment.With the development of nanotechnology,it is now possible to utilize nanovehicles carrying conventional chemotherapy drugs to alter their pharmacokinetic profiles,improve water solubility,increase tumor targeting,and reduce side effects.One common example is that human serum albumin(HSA)is used to carry paclitaxel(PTX)to improve its water solubility.An albumin-bound nanocomplex(Abraxane?)was approved by the United States Food and Drug Administration(U.S.FDA)for the management of breast cancer,non-small cell lung cancer,and pancreatic cancer by itself or in combination with other medications.Despite the success,there are many significant side effects at high doses and a tendency to induce drug resistance of such chemotherapy agents.Combination therapy is an ideal strategy to improve therapeutic efficacy,reverse drug resistance,and minimize side effects.In particular,combination of photothermal therapy(PTT)and chemotherapy can be simultaneously delivered by nanoscale agents and has attracted tremendous attentions in recent years.Generally,PTT employs photothermal conversion agents(PTCAs)to convert photon energy into cytotoxic heat to treat a variety of diseases including cancer with a minimum thermal injury to normal tissues.As compared to conventional cancer treatment approaches,PTT is highly localized and can be applied in regions where surgery is difficult.More importantly,it has been reported that in combination with chemotherapy,photothermal heating can simulate the cell internalization of chemotherapy drug,increase drug release from the nanocomplex and even improve drug extravasation from tumor microvasculature to elevate the cancer treatment effect in a synergistic way.Here,we report a chemotherapy combined with photothermal therapy(PTT)for enhanced cancer treatment effect by functionalization of gold nanorods(GNR)with a novel small molecule named truncated Evans Blue(tEB).Because of the high binding affinity between tEB and albumin,an Abraxane-like nanodrug,human serum albumin/hydroxycamptothecin(HSA/HCPT),was further complexed with GNR-tEB.This formed an HCPT/HSA/tEB-GNR(HHEG)with excellent biostability and biocompatibility.Based on photoacoustic and fluorescence imaging,we observed enhanced permeability retention(EPR)effect mediated HHEG tumor targeting.The HHEG peaked in the tumor area at 12 h post-injection.Moreover,HHEG can effectively ablate tumor growth with laser illumination via chemo/thermal therapy after intravenous administration into SCC7 tumor.This combination is much better than chemotherapy or photothermal therapy alone.Collectively,we constructed a chemo/thermal therapy nanostructure based on a tEB-modified GNR for better tumor treatment effect.The use of tEB in gold nanoparticles can facilitate many new approaches to designing hybrid nanoparticles.