Photoresponse Performance And Anti-tumor Study Of Platinum/Gold Nano Drug Delivery System

In recent years,the incidence and mortality of cancer are growing rapidly.The complex variability of tumors makes the cure rate of tumors unsatisfactory.Delightedly,the emergence of near-infrared?NIR?light-responsive nanocarriers provides new hope for tumor therapy.Under the irradiation of NIR light,nanocarriers can realize the responsive release of drugs on demand.Recently,noble metal nano drug delivery systems have become a hotspot in the field of cancer therapy due to their unique optical,catalytic and anti-tumor properties through sophisticated synthesis.In this study,gold and platinum nanomaterials were used to construct four different light-responsive nanodrug delivery systems by combining with drug carriers such as liposome and polydopamine.Further analyze the anti-tumor mechanism of noble metal nanomaterials the light-responsive performance of the nanocarriers.The specific research contents are as follows:?1?Triptolide-coated liposomes coated with gold nanospheresTriptolide?TP?was selected as an antitumor drug,which was loaded into liposomes by ethanol injection.Subsequently,a layer of chitosan was modified on the surface of liposome,then gold nanospheres coated TP liposomes?AuNS-CS-TP-Lips?were synthesized by seed growth method.Due to the unique optical properties and the surface plasmon resonance effect of the gold nanoshells,AuNS-CS-TP-Lips could absorb NIR light and convert it into heat energy.On the one hand,the heat produced directly ablated the tumor cells;on the other hand,it could cause a phase change of the liposome membrane and promote the light-responsive release of TP.At the same time,in the tumor acidic environment of pH 5.5,the amino group of chitosan was protonated,which weakened the interaction between the drug and nanocarriers,and achieved a rapid release of pH responsiveness of TP.Cell experiments and animal experiments demonstrated that AuNS-CS-TP-Lips achieved a synergistic effect of photothermal therapy?PTT?and chemotherapy after NIR light irradiation.?2?Platinum/gold bimetallic nanoshells coated triptolide liposomeBimetallic colloids are more functional nanomaterials than single metal nanoparticles.In this study,based on the gold nanoflower-coated TP liposome?AuNF-TP-Lips?,a layer of platinum nanoparticles was bonded to the outer layer of the nanoflower by electrostatic deposition to obtain Pt/Au bimetallic nanoshells coated triptolide liposome?Pt@Au-TP-Lips?.Due to the resonance coupling between the Pt/Au bimetallic core-shell and the high absorption/scattering ratio of platinum nanoparticles,the photothermal conversion performance of Pt@Au-TP-Lips was significantly improved.Under NIR light irradiation,Pt@Au-TP-Lips achieved light-responsive release of the drug.Cellular uptake experiments have shown that hyperthermia could promote the cellular internalization of nanoparticles.Additionally,in the tumor microenvironment?acidic,oxidative and so on?,Pt can be converted to Pt²⁺,causing DNA double-strand structure destruction.Cell experiments and animal experiments show that Pt@Au-TP-Lips achieves the synergistic effect of PTT and double-drug(TP,Pt²⁺)chemotherapy by NIR light irradiation,and achieved good anti-tumor effect.?3?Platinum/gold bimetallic nanoshells coated chlorin e6/resveratrol liposomeOn the basis of Pt@Au-TP-Lips,the photosensitizer chlorin e6?Ce6?and the chemotherapeutic drug resveratrol?Res?were simultaneously loaded into the liposome.A Pt enhanced phototherapy/chemotherapy drug-loaded liposome?Pt@Au-Ce6/Res-Lips?was synthesized.Pt possessed excellent catalase-like activity and could catalyze the decomposition of endogenous H₂O₂ in the tumor site to produce O₂,which relieved the limitation of hypoxia on PDT and enhanced the PDT effect.Further combined with the photothermal effect of gold,the Ce6 and Res achieved responsive release.Cell experiments and animal experiments showed that Pt@Au-Ce6/Res-Lips achieved the combined action of chemotherapy,PTT and PDT under the sequential irradiation of NIR light at 808 nm and 660 nm.Additionally,Pt enhanced the PDT performance in hypoxic environment and achieved excellent tumor suppression.?4?Biomimetic polydopamine/glucose oxidase/doxorubicin coated platinum nanospheresBased on Pt catalase-like performance enhanced PDT effects,we synthesized a self-enhanced starvation therapy/chemotherapy/PTT/oxidative stress therapy nanocarrier.Firstly,the platinum nanospheres?PtNS?were prepared by template method,and then the PDA was adhered uniformly to the surface of PtNS.Furthermore,glucose oxidase?GOx?and anticancer drug doxorubicin?DOX?were loaded in polydopamine?PDA?with?-?interaction and covalent bonds to obtain Pt@PDA/GOx/DOX nanoparticles.After that,homologous tumor cell membrane was modified on to finally obtain the biomimetic Pt@PDA/GOx/DOX@C.The experimental results showed that Pt@PDA/GOx/DOX@C could achieve PTT and responsive release of drugs under the irradiation of NIR light due to the photothermal performance of PDA.Then the released GOx could catalyze the decomposition of glucose in the tumor microenvironment to produce H₂O₂ and gluconic acid and achieve the purpose of starvation.Furthermore,H₂O₂ activated the catalase-like activity of Pt to generate a large amount of O₂,which enhanced the effect of starvation treatment.Meanwhile,gluconic acid caused pH decrease to activate the oxidase-like activity of Pt,and produced much ROS,which on one hand induced apoptosis of tumor cells,on the other hand oxidized PtNPs into Pt²⁺to achieve the effect of combined chemotherapy with DOX.Cell uptake experiments demonstrated that homologous cell membranes could enhance the internalization of nanoparticles,and cell experiments and animal experiments have demonstrated that nanocarriers with self-enhanced starvation/chemotherapy/PTT achieve superior antitumor effects.In summary,this study constructed four NIR light-responsive drug delivery systems.By combining platinum and gold nanomaterials with drug nanocarriers,the light-responsiveness mechanism of nanocarriers and the anti-tumor mechanism of gold and platinum nanomaterials were deeply explored.This work will lay the foundation for future cancer treatment.