Study On Adsorption And Release Of Antineoplastic Drugs By Carbon-based Metal Nanocomposites

As a traditional treatment,chemotherapy is still one of the necessary ways to treat cancer,but most antineoplastic drugs have many shortcomings,so the construction of appropriate drug carriers has become the focus of research to alleviate or overcome their adverse reactions.Carbon-based metal nanocomposites can be combined with the properties of drugs to design the structure,composition and even additional functions of materials.For example,for insoluble drugs,drug dissolution can be increased by reducing drug crystallinity.In this study,ZIF/AG-CAs magnetic drug carriers were prepared,and its rich pore structure can increase the drug release rate.For drugs with a short half-life,drug release can be sustained through pore encapsulation and enhanced adsorption.In this study,Au@Pt_1.5Co_0.08/CNT drug carrier was designed,whose strong metal-molecular bond can greatly promote drug adsorption and drug release.For drugs with low cell selectivity and many adverse reactions,magnetic targeting and/or light-controlled release strategies can be used to make up for the shortcomings.Therefore,based on local surface plasmon resonance excitation（LSPR）,a photoresponsive Cu Pt Ni_0.23/CNT drug carrier was designed.It was found that light could significantly promote drug release in vitro,and further explored the effect of photoexcited hot electrons on photocontrolled drug release.In addition,the field of nano-catalysis medicine combines the two disciplines of nano-catalysis and nano-medicine,which can trigger specific catalytic reactions in the body to achieve the purpose of treating diseases.Through the reasonable design of the catalyst,the change of microenvironment in the organism can be controlled by catalytic reaction,so as to improve or enhance the therapeutic effect.Therefore,the study of the catalytic performance of carbon-based metal nanocomposites is of great value in the field of nano-catalytic medicine.The main research contents are as follows:1.With the combination of biomass agarose gel（AG）and metal-organic skeleton（MOF）,three-dimensional layered porous carbon aerogel ZIF/AG-CAs was prepared by freeze-drying and high-temperature carbonization.Compared with ZIF-NC,carbon aerogel has rich pore structures such as micropore and mesopore.Co NPs in ZIF/AG-CAs can also provide excellent magnetic properties for targeted drug delivery and clinical diagnosis.Dacarbazine（DTIC）was used as a model drug,and the drug carrier complex was detected by XRD,FT-IR,and TG to determine whether the drug was loaded successfully.The loading,in vitro dissolution and p H response of DTIC-ZIF/AG-CAs to DTIC were studied,and the stability and cytotoxicity of drug carrier complexes were also tested.The results show that the drug loading of DTIC-ZIF/AG-CAs is as high as 47.63%,and the composite has good magnetism,stability and low cytotoxicity,and the suitable dosage of the preparation is 0-100μg/m L.2.Carbon-based metal nanocomposites such as Au@Pt_1.5Co_0.08/CNT,Au@Pt_1.5/CNT and Pt_1.5Co_0.08/CNT were prepared by chemical reduction method.5-fluorouracil（5-FU）was used as a model drug,Au@Pt_1.5Co_0.08/CNT with the highest drug loading was selected（51.32%）.The successful loading of the drug was proved by XRD,FT-IR,and TG.The in vitro dissolution and stability of drug carrier complex 5-FU-Au@Pt_1.5Co_0.08/CNT were tested in different dissolution media,and its cytotoxicity was further investigated.The results showed that the release of5-FU from 5-FU-Au@Pt_1.5Co_0.08/CNT slowed down obviously.Combined with XPS and synchrotron radiation analysis,it was found that the high drug loading and slow drug release were due to the unique electronic structure of metal NPs,which improved the adsorption intensity of drug molecules.5-FU-Au@Pt_1.5Co_0.08/CNT also has good stability and low cytotoxicity,and its dosage is suitable in the range of 0-100μg/m L.3.In this study,Cu Pt/CNT and Cu Pt Ni_0.23/CNT photoresponsive composites were prepared by using cheaper Cu as plasma metal.Cyclophosphamide（CTX）was used as a model drug,and the carrier material Cu Pt Ni_0.23/CNT with the highest load was selected（43.58%）.It was proved that CTX was successfully loaded on Cu Pt Ni_0.23/CNT by XRD,FT-IR,and TG characterization.The dissolution experiment of CTX-Cu Pt Ni_0.23/CNT in vitro and the effect of light on the dissolution of CTX were studied,and its stability and cytotoxicity were tested.The results showed that Cu Pt Ni_0.23/CNT could significantly slow down the release of CTX drugs,and light could significantly promote the dissolution of CTX drugs,and the rate of drug release from CTX-Cu Pt Ni_0.23/CNT was faster than that of CTX-Cu Pt/CNT.Through the study of transient absorption spectra,it is found that the photoexcited electrons of Cu Pt Ni_0.23 have a longer lifetime and higher energy than those of Cu Pt.CTX-Cu Pt Ni_0.23/CNT also has good stability and low cytotoxicity,and its dosage is suitable in the range of 0-1000μg/m L.4.Carbon-based metal nanocomposites also play an important role in the field of catalysis,and their unique electronic structure is conducive to the adsorption and desorption of intermediates in the catalytic reaction.As an“inert gas”in the body,hydrogen can selectively react with toxic free radicals such as hydroxyl radicals and nitrite anions in tumor cells,so as to destroy the microenvironment of tumor cells.Therefore,based on the intrinsic activity of Pt on electrocatalytic hydrogen evolution reaction（HER）,this study also explored the application of Au@Pt_1.5Co_0.08/CNT and Cu Pt Ni_0.23/CNT nanocomposites in HER,they all showed good HER performance,and Cu Pt Ni_0.23/CNT significantly improved the performance of HER under light-assisted electrocatalysis.Through further modification and design,these excellent HER catalysts are expected to catalyze the decomposition of H₂O to H₂ in vivo,and then H₂ and loaded chemotherapeutic drugs can kill tumor cells in coordination.