Application Of Reduced Graphene Oxide Combination Therapies For Cancer

Cancer is a serious disease that challenges the survival of people in all age groups,especially those living in developed countries.In cancer clinical treatment,chemotherapy(CT)is still the most widely used method.However,some shortcomings such as killing health cells simultaneously ruesulting in severe toxic side effects have limited its application.Recently,some novel and effective therapeutic methods such as photothermal therapy(PTT)and photodynamic therapy(PDT),have attracted more and more attentions due to their small invasiveness and simple operation.Especially,the combination of PTT or PDT with chemotherapy not only overcome chemotherapy shortcomings but also effectively inhibit tumor cells with improved therapeutic efficacy.In this thesis,we chosed reduced graphene oxide(rGO)as backbone and photothermal agent to fabricate PTT/CT and PTT/PDT/CT combined therapy systems.Mainly include the following parts:1.Graphene-based materials show great potential in photothermal therapy,but their photo-thermal conversion efficiency needs to be improved.Herein,a facile and low-cost strategy had been presented to grow Au clusters on the reduced graphene oxide(rGO)sheets to improve photothermal effect.Au clusters with low-concentration was directly conjugated on the surface of rGO by electrostatic forces.To improve its biocompatibility,3-(3-phenylureido)propanoic acid(PPA)-PEG(PPEG)had been introduced as biodegradable backbone to form rGO/Au/PPEG nanohybrids via ?-? accumulation.The modified rGO/Au/PPEG not only show excellent biocompatibility and stability,but also improve the efficiency of light-heat conversion.The rGO/Au/PPEG nanohybrids was demonstrated by FI-IR,Raman,TGA,XPS,TEM images and DLS.Doxorubicin(DOX),a model of anti-tumor drugs,was loaded into rGO/Au/PPEG nanohybrids through ?-? stacking,and to verified the tumor inhibition effect of its photothermal-chemotherapy combination therapy.The obtaided experimental results indicated that compared with single chemotherapy,rGO/Au/PPEG/DOX nanohybrids have a higher therapeutic effect on tumors.2.To improve the local therapeutic efficacy,a kind of photosensitizer,porphyrin,had been introduced.In this strategy,tetrahydroxyphenylporphyrin(THPP)was used as a photosensitizer,and carboxylated polyethylene glycol(PEG-COOH)was esterified to produce a photosensitizer-modified polymer backbone THPPEG.Among them,rGO was used as a photothermal agent and drug carrier,then the THPPEG was modified onto rGO surface by ?-? stacking interaction to prepare rGO/THPPEG nanoparticles.The obtained rGO/THPPEG not only showed good biocompatibility and water solubility,but also realized the combination of PTT with PDT.The nano-sized,structurally stable rGO/THPPEG nanoparticles was demonstrated by FI-IR,Raman,TGA,XPS,TEM images and DLS.To further evalue the PTT-PDT-CT therapeutic efficacy,Doxorubicin(DOX)was used as an anti-tumor drug model,and was loaded to prepare drug-loaded rGO/THPPEG/DOX.The experimental results showed that PTT-PDT of rGO/THPPEG was superior to single therapy,the combined application of PTT-PDT-CT with rGO/THPPEG/DOX could more effectively inhibit tumor growth.