Study On Carbon Nanomaterial Based Tumor Targeting Drug Delivery System

Fullerene (C60), carbon nanotube (CNT) and graphene oxide (GO) had lowsystemic toxicity, they could efficiently cross cell membranes and load a large amoutof antitumor drugs, in addition, C60could be used in photodynamic therapy owingto its ability of efficiently generating ROS under visible or UV light irradiating,CNT and GO could be used in photothermal therapy for their capability oftransforming near-infrared light (NIR) into heat. Take the above carbonnanomaterial and chemotherapy drugs into one system, could achievechemo-photodynamic therapy or chemo-photothermal therapy effect to treat tumors.In this study,5tumor targeting drug delivery systems were developed in order toimprove the efficacy of chemotherapy drugs and reduce their side effects.1Investigation of a tumor targeting drug delivery system based onpolyethyleneimine-derivatized C60To improve the biocompatibility of C60, a water-soluble polymerpolyethyleneimine (PEI) was introduced to the surface of C60via a cationicpolymerization of aziridine, and then the tumor targeting molecules folic acid (FA)were linked to C60-PEI, furthermore, the antitumor drug docetaxel (DTX) wereloaded, herein, a DTX tumor targeting nano drug delivery system(C60-PEI-FA/DTX) was developed. The in vitro studies showed: C60-PEI-FA/DTXcould efficiently target to human prostate cancer (PC3) cells, and cross cellmembranes, finally inhibit the growth and proliferation of PC3cells. The in vivostudies showed: C60-PEI-FA/DTX showed very low toxicity, significantlyprolonged the blood ciculation of DTX, and brought more DTX to tumor, finallyinhibited the growth of tumor.2Study on a C60based pH-responesive drug delivery system and itsphotodynamic therapyIn order to reduce the toxicity of doxorubicin (DOX), DOX was covalentlyconjugated onto C60-PEI by the pH-sensitive hydrazone linkage, obtaining a nano delivery system (C60-PEI-DOX) with pH-sensitive, chemotherapeutic andphotodynamic therapeutic functions. The in vitro studies showed: C60-PEI-DOXcould cross the cell membranes of mouse melanoma (B16-F10) cells within2h, andinhibit the growth and proliferation of B16-F10cells by releasing DOX in cytoplasm;in addition, C60-PEI-DOX could efficiently generate ROS under532nm laserirradiation, injure nuclear DNA of B16-F10cells and lead to cell apoptosis; thechemotherapy induced by DOX and photodynamic therapy induced by C60-PEI hada good synergistic enhancement. The in vivo studies showed: C60-PEI-DOX couldefficiently accumulate in tumor, explosively release DOX due to the acidicenvironment of tumor, while the release rate of DOX was very low in the normaltissues and blood, this improved the efficacy of DOX and reduced its toxicity;moreover, C60-PEI-DOX with laser irradiation exhibited a good photodynamicactivity, and photodynamic therapy combined with chemotherapy had a synergisticenhancement of tumor therapy.3Study on a magnetic C60based multi-functional tumordiagnosis-photodynamic therapy delivery systemIn order to improve the photodynamic efficacy of a small molecularphotosensitizer hematoporphyrin monomethyl ether (HMME), firstly, iron oxidenanoparticles (IONP) were decorated onto the surface of C60, and then PEGylationwas performed, obtain a magnetic C60derivative C60-IONP-PEG. HMME wasconjugated to C60-IONP-PEG, forming a nano drug delivery system(C60-IONP-PEG/HMME), which demonstrated magnetic targeting-magneticresonance imaging-photodynamic therapeutic abilities. The in vitro studies showed:C60-IONP-PEG/HMME could efficiently cross the membranes of B16-F10cells,and take HMME to the cell nuclei, both C60and HMME could efficiently generateROS under the laser irradiation, and C60-IONP-PEG/HMME greatly improved thephotodynamic efficacy. The in vivo studies showed: C60-IONP-PEG/HMME couldsignificantly prolong the blood ciculation of HMME, when the tumor site had amagnetic field, C60-IONP-PEG/HMME could accumulate in tumor efficiently,when irradiating with laser, both C60and HMME exhibited the photodynamic activities at the same time, and this greatly improved the efficacy of photodynamictherapy. In addition, the T2weighted signal in tumor site greatly decreased afterinjection of C60-IONP-PEG/HMME, suggesting C60-IONP-PEG/HMME can act asa suitable contrast agent for tumor diagnosis in magnetic resonance imaging.4Study on a CNT based tumor photodynamic-photothermal combinedtherapeutic systemTo improve the water-solubility of CNT, a tumor targeting polysaccharidehyaluronic acid (HA) were introduced to the surface of CNT, next, HMME wasloaded onto CNT-HA by π-π stacking, herein, a photodynamic-photothermalcombined therapeutic system (CNT-HA/HMME) was developed. The in vitrostudies showed: CNT-HA/HMME could efficiently cross the cell membranes ofB16-F10cells, and enhance the photodynamic activity of HMME, the photodynamictherapy induced by HMME and photothermal therapy induced by CNT-HA had asynergistic enhancement of killing tumor cells. The in vivo studies showed:CNT-HA/HMME had a low toxicity, and the system could accumulate in tumor viaEPR effect and the tumor targeting effect of HA, CNT-HA/HMME exhibited astronger photodynamic activity than HMME, and the photodynamic therapy inducedby HMME and photothermal therapy induced by CNT-HA exhibited an obvioussynergistic effect.5A tumor targeting light-controlled drug delivery system based on GO/Ag fortumor theranostic applicationsIn order to improve the efficacy and reduce the toxicity of DOX, Agnanoparticles were decorated onto the surface of GO, and DOX was linked via esterbonds, then GO@Ag-DOX was functionalized by DSPE-PEG-Maleimide (DPM) toimprove its biocompatibility, furthermore, a tumor targeting peptide NGR wasconjugated to GO@Ag-DOX. Taking advantage of the NIR-triggered excitedelectrons transfer from Ag nanoparticles because of SPR effect, a nano drug deliverysystem (GO@Ag-DOX-NGR) with tumor targeting, photothermal therapeutic,NIR-controlled drug releasing and X-ray imaging abilities was developed. The invitro studies showed: GO@Ag-DOX-NGR obviously targeted to human breast cancer (MCF-7) cells, under the NIR irradiation, GO@Ag-DOX-NGR could notonly explosively release DOX, but also generate a large number of heat, achievingsynergistic enhancement of killing tumor cells by combining chemotherapy withphotothermal therapy. The in vivo studies showed: GO@Ag-DOX-NGR with NIRlaser could significantly improve the efficacy and reduce the toxicity of DOX. Andthe high efficacy and low toxicity of GO@Ag-DOX-NGR originated from the highDOX concentration in tumor, photothermal effect and the explosive releasing ofDOX under NIR laser. Moreover, GO@Ag-DOX-NGR also had a potential in X-rayimaging.The above studies explored the applications of carbon nanomaterial in tumordiagnosis and therapy, and this study provided a new idea for tumor diagnosis andtreatment.