Investigation Of The Sers And Drug Release Properties Of Nanocarrier Based On Carbon Nanotube/metal Nanocomposites

Recently,nano-drug carriers in cancer treatment research have received widespread attention.Transporting anticancer drugs to the tumor site can increase the concentration of drug in tumor cells,which can improve the therapeutic efficacy of tumor and reduce the toxicity to normal tissue.However,the therapeutic effect of nano-drug carriers did not only depend on the accumulation of drugs in tumor site,but also be affected by drug release properties.Therefore,it is very important to study the intracellular drug release properties.Due to the special 1-D tubular structure,easiness to be functionalized and strong cells penetrating ability,carbon nanotube(CNT)has been widely used in nano-drug carrier research.In this work,we develop a controllable drug nanocarrier based on carbon nanotube for tumor diagnosis and treatment.By using carbon nanotube/metal nanocomposite structure,we successfully fabricated a intracellular pH sensor based on SERS technique and a traceable nanocarrier to realize drug controlled release and real-time monitor drug release in the tumor cellsFirst,we propose a pH-sensitive probe based on Au@Ag/CNT for intracellular pH sensing.This probe can effectively detect the pH value of external environment with good biocompatibility.We have succeeded in using this probe to detect pH distribution in a single cell.This new probe also shows a wide range for pH sensing and good biocompatibility which holds a potential application in the bioanalysis.Second,Au@Ag/CNTs nanoparticles as pH-sensitive nanocarrier can be used for tracing drug release in living cells.Doxorubicin(DOX),an antitumor drug,is loaded on the surface of the CNT,which can be realeased in acid condition.Au@Ag/CNTs is labeled cooperatively by 4-mercaptobenzoic acid(4MBA)and fluorescein isothiocyanate(FITC),which served as pH sensor and fluorescent tracker,respectively.By tracing the fluorescence of DOX and SERS signals of carrier inside cells,we have effectively monitored the internalization process of carrier and the dynamic release of DOX in living tumor cells.Third,we fabricated a 6-thioguanine(6TG)and doxorubicin(DOX)codelivery nanocarrier based on Au@Ag/CNT to obtain effective combination therapy.The release of 6TG and DOX were triggered by the glutathione(GSH)and the acidic environment of lysosomes,respectively.Moreover,by using label-free SERS and fluorescence techniques,the release dynamics of the loaded two drugs can be traced in living cells.Besides,we also have demonstrated that Au@Ag/CNT can function as controllable delivery vehicle to encapsulate indole inside their hollow tunnels and load DOX on their outer surface.CNT/Au@Ag can release indole under near-infrared(NIR)irradiation and release DOX inside lysosome,respectively.Finally,the experimental results confirmed that this combination of dual-drug exhibited a synergistic effect to improve the efficacy of cell-killing.