Gold Nanorod/nanomedicine Supermolecular Hydrogel For Synergetic Cancer Therapy

Though different treatments emerged constantly,cancer still remains one of the world’s most overwhelming diseases leading cause of death.Systemic chemotherapy has been commonly used in clinic,of which the therapeutic efficiency is limited by the severe side effects and the extensive multi-drug resistance.As a new treatment,photothermal therapy has the advantages of minimal invasiveness,high time-space controllability,strong tumor specificity and low systemic cytotoxicity.The precise locoregional co-delivery of multi-agents is an attractive strategy.In order to achieve superior synergistic therapeutic effects,the emergence of an ideal injectable hydrogel platform with good biocompatibility and multi-component compatibility is urgently needed.Herein,an injectable nanocomposite hydrogel was fabricated for local chemo-photothermal synergetic cancer therapy.The methoxy poly（ethylene glycol）-b-poly（ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone）（m PECT）diblock copolymer was empolyed to prepare the m PECT-modifieid gold nanorods（Au NR-PECT）.Then,an injectable nanocomposite hydrogel(^{Au NR/PTX}m PECT^gel)was fabricated by the host-guest inclusion between Au NR-PECT,PTX/m PECT NPs andα-cyclodextrin.Rheology studies have shown that the gel has shear thinning properties and maintained its original gel state at elevated temperatures and suitable shear forces.The stability and the in vitro and in vivo photothermal effect experiments have proved that ^{Au NR/PTX}m PECT^gelhas excellent stability and photothermal conversion ability.The in vitro degradation and PTX release of ^{Au NR/PTX}m PECT^gelunder 808 nm illumination showed that the gel degradation and drug release behavior were not affected by the illumination,and remained at a certain speed and continued to be stable,which was beneficial to the later implementation of in vivo photothermal therapy.In addition,photothermal effect of Au NR-m PECT can effectively kill 4T1 cells,and chemotherapy-photothermal combined treatment on cancer cells is significantly stronger than other monotherapy.Single local injection of ^{Au NR/PTX}m PECT^gelcould depot abundant PTX/m PECT NPs（20%w/w）and Au NRs at the target location,which then sustainedly release PTX/m PECT NPs at a constant rate for two weeks as well as exhibit outstanding photothermal effect by near-infrared radiation.As a result,excellent chemo-photothermal synergetic anticancer effects(complete tumor regression after peritumoral injection of ^{Au NR/PTX}m PECT^geland effectively inhibition of tumor recurrence after injection on postoperative cavity)with reduced side effects were obtained on breast cancer mouse models.Furthermore,the strategy of nanocomposite hydrogel co-constructed by supramolecular assembly could be facilely extended to other local combination therapies of different nano theranostic agents.