Building Of Functional Amphiphilic Supramolecular Systems Based On Pillar [5] Arene And Synergistic Drug Delivery Treatment

In recent decades,nanotechnology has developed rapidly.Scientists have devoted themselves to the development of a novel drug nanocarrier-drug delivery system that uses tumor tissue to carry antitumor drugs.The drug delivery system can carry antitumor drugs to tumor tissues,then using the tumor microenvironment to stimulate the release of loaded drugs,achieve the treatment of tumors intelligently and accurately,and at the same time,it can effectively reduce the toxic side effects of drugs on normal cells or tissues.The host-guest chemistry has excellent advantages due to its selectivity,high efficiency,and stimuli-responsiveness.The new generation host of pillar arene,with unique structure,excellent properties,and rich stimuli responsiveness,has been widely used in the field of drug transportation.In order to further improve the effect of cancer treatment and reduce the toxic and side effects,the development of supramolecular vesicles for the combined treatment of tumors based on columnar aromatics has become one of the research hotspots.Photothermal therapy and photodynamic therapy are the new technologies for cancer treatment,which is the first choice with synergistic therapy.Photothermal Therapy generally uses materials with near-infrared absorption,which has a high light-to-heat conversion efficiency,and it's also accumulates materials in the tumor tissue through targeted recognition or drug transport.Under the irradiation of near-infrared lasers,it can convert light energy into heat energy for tumor treatment.Photodynamic Therapy is a non-invasive method of cancer therapy.Including photosensitizer,light and tissue oxygen,they can generate reactive oxygen species?ROS?,and use active oxygen to kill cancer cells to cure cancer.Photodynamic therapy has become a common treatment for cancer therapy because of its advantages of minimal surgical trauma,low toxicity,good selectivity,and good applicability.Based on the water-soluble pillar[5]arene,this paper designs and synthesizes the guest with different properties,constructs amphiphilic supramolecular vesicles with high drug loading and stimuli-responsiveness.And some basic in vitro biological properties have been studied.?1?First,the water-soluble main pillar[5]arene was designed and synthesized,and then a PDI-based guest G1 was synthesized.The study of host-guest interaction showed that the optimal molar ratio of the supramolecular vesicles was[WP5]/[G1]=1:5,?-potential=-30.7 mV.Then,the anticancer drug doxorubicin?DOX?was loaded into the WP5?G1 vesicles,and the DOX loading rate was 27.2%.This drug delivery system showed pH stimuli responsiveness.The vesicle disassembled and DOX released in weak acid environment.The release rate of DOX,pH 6.2,and pH 4.4 were 62.4%and 80%,respectively.Secondly,G1 is a photosensitizer for photothermotherapy.The maximum temperatures could reach at 68.2°C and 62.4°C at a wavelength of 730 nm laser for 10 min at 0.2 mM G1 and WP5?G1 respectively,and the photothermal conversion efficiency was up to 50.9%and 44.5%,respectively.At the same time,in vitro toxicity studies have shown that supramolecular drug-loaded vesicles not only have the anticancer activity of DOX,but also exhibit strong photothermal therapeutic properties.?2?A guest G2 which based on pyrrolopyrrolidone was designed and synthesized.The study of host-guest interaction showed that the optimal molar ratio for constructing supramolecular vesicle was[WP5]/[G2]=1:5,?-potential=-30.47 mV.Then,the anticancer drug MTZ could be loaded into WP5?G2 vesicles,and the MTZ loading rate was up to 45.8%.This drug delivery system showed pH stimuli responsiveness.The vesicle ruptured and MTZ released in weak acid environment.The release rates of pH 6.8,pH 5.5,and pH 4.0 were 34.5%,68.8%,and 96.9%,respectively.Secondly,as a photosensitizer for photodynamic therapy,G2 can generate singlet oxygen?¹O₂?at a wavelength of 532 nm laser.At the same time,MTZ can effectively absorb the fluorescence of G2,and the fluorescence signal of the drug-loaded vesicles can be used as a fluorescent probe.The vitro toxicity studies have shown that the supramolecular drug-loaded vesicles not only have the anti-cancer activity of MTZ,but also have a certain photodynamic anti-cancer activity.From this,it can be seen that the novel drug delivery system of pH-stimulation-responsive co-treatment constructed in this study has potential application value.