The Construction Of Dual-targeting Graphene Oxide Nano-drug Delivery System And The Study On Its Synergisitic Chemo-photothermal Cancer Therapy

Recently,owing to lack specificity for caner cells and low stability,clinical anti-tumor drugs suffer from low chemotherapeutic efficacy with severe side effects and multidrug resistance.Hence,current research has focused on designing original nano-drug,which has many advantages like active targeting effects,considerable stability,integration of diagnosis and treatment.As a new anti-tumor therapeutic method,photothermal therapy(PTT)possesses distinctive advantages such as fewer complications and shorter recovery time than traditional therapy.Moreover,when PTT is combined with chemotherapy,tumor cells can be more efficiently killed by joint effects of anti-tumor drug and local hyperthermia.Graphene oxide(GO),a kind of two-dimensional nanomaterial,can serve as desired carrier for drug delivery because of its large surface areas.Besides,GO has huge potential for PTT since it shows high NIR absorbance and photothermal conversion efficiency.However,drugs are always carried on GO through ?-? stacking and hydrophobic interaction,which will suffer from great losses at physiological environment in vivo.Eventually therapy effects will be pretty weak owing to low drug content at tumor sites.More seriously,GO has toxicity for cells and tissues.To overcome above-mentioned weakness,GO-HA-MTX conjugate is designed in this study.To construct GO-HA-MTX conjugate,carboxyl-functionalized GO is firstly synthesized,and then grafted by hyaluronic acid(HA)-methotrexate(MTX)prodrug through chemical bond.Herein,HA is designed to improve stability and biocompatibility of GO and simultaneously play the part of targeting moiety for CD44 receptors.As antimetabolitas for cancer treatment,MTX can also act as targeting moiety for FA receptors.Therefore,GO-HA-MTX conjugate can serve as nanosystem for drug delivery with dual active targeting effects,applying for chemo-PTT synergy.GO,GO-HA,and GO-HA-MTX are successfully constructed,which is subsequently identified by FT-IR,UV-vis absorption,XRD,size and zeta test.According to cytotoxicity,cellular uptake,in vivo fluorescent imaging,and anti-tumor efficacy studies,it is approved that GO-HA-MTX nano-drug delivery system can achieve tumor elimination without reappearance in the dual-targeting mechanism without reappearance through synergisitic chemo-photothermal cancer therapy.It is of great significance for multimode treatment of tumor.