Fabrication Of Gold Nanorod@porphyrin MOF Composite For Synergistic Chemodynamic And Photothermal Therapy

Cancer is a kind of disease that seriously endangers human health and life.The development of cancer treatment methods has always been the focus of scientific and clinical research.In view of the high cost and obvious toxic and side effects of traditional chemotherapy,surgery,radiation therapy and other treatment methods,it is very important to develop new high-efficiency,low-toxicity and precise tumor treatment strategies to improve the cure rate of cancer and reduce the burden on patients and the medical system.For specific tumor microenvironments,including low p H,excess H₂O₂,and hypoxia,chemodynamic therapy（CDT）using endogenous H₂O₂ for nanocatalytic reactions to generate reactive oxygen species has great potential treatment method.Among them,the typical one is to use the Fenton reaction to catalyze the overexpressed H₂O₂ in the tumor microenvironment to generate highly toxic hydroxyl radicals（·OH）,thereby efficiently killing tumor cells.This method has the advantages of endogenous activation,high selectivity,and clear logic.However,the low catalytic efficiency in the tumor region and the poor efficacy of CDT hinders its further application in tumor therapy.Recently,the strategies of photothermal enhancement and self-contained H₂O₂ can effectively enhance the performance of CDT.Photothermal Therapy（PTT）is a treatment method that uses the photothermal effect of materials to generate high temperature at the tumor site to kill tumor cells.Gold nanorods（GNR）are classic high-efficiency photothermal materials with high photothermal conversion efficiency,good biocompatibility,and their absorption peaks are located in the near-infrared region,which is conducive to penetrating deep subcutaneous tissues.Therefore,the composite preparation of iron-based CDT materials and GNR into nanomaterials with suitable size is expected to realize the synergistic treatment of photothermal enhanced CDT and obtain efficient tumor treatment effect.Based on the above assumptions,our work is as follows:1.Starting from the interfacial compatibility between porphyrin MOF and inorganic GNR,the surface ligands of GNRs were replaced with small molecule 11-mercaptoundecanoic acid（MUA）to obtain gold nanorods（MUA-GNR）with carboxyl groups on the surface.Then,the porphyrin MOFs were assembled on the surface of gold nanorods in an orderly manner by the"seed replacement method",and the reaction temperature,concentration of gold nanorods,reaction time and other conditions were adjusted to obtain two gold nanorod@porphyrin MOFs with different morphologies（GNR@TCPP-MOF）core-shell nanomaterials.The GNR@TCPP-MOF was systematically analyzed by SEM,TEM,Mapping,XRD,UV-vis absorption and other characterization methods.The results show that the introduction of gold nanorods has a great influence on the morphology and size of the composite material,and the composite material has both the excellent properties of porphyrin and gold nanorods.Different metalloporphyrins were prepared from tetracarboxyphenylporphyrin by metallization,and then different metalloporphyrins were compounded with GNRs to obtain a series of gold nanorods@metalloporphyrin MOF composite materials.Through literature research and experimental screening,it is found that the synthesized flower-like gold nanorod@iron porphyrin MOF（GNR@Fe TCPP-MOF）composite has good chemical kinetics and photothermal properties,and the size is about 190 nm,which is suitable for biological system.GNR@Co TCPP-MOF and GNR@Zn TCPP-MOF have strong fluorescence properties,and GNR@Fe TCPP-MOF has good MRI imaging function.Both imaging modes can be used for real-time monitoring and treatment of subsequent tumor-bearing mouse experiments.The photothermal properties,chemical kinetic properties and photothermal enhanced chemical kinetic properties of GNR@Fe TCPP-MOF composites were tested.It shows that the GNR@Fe TCPP-MOF composite has better photothermally enhanced chemical kinetic properties.2.In order to increase the phagocytosis of nanomaterials by cells,GNR@Fe TCPP-MOF nanomaterials were targetedly modified with cell-penetrating peptides（TAT）,and GNR@Fe TCPP-MOF materials were used in in vivo and in vitro antitumor experiments.First,the test of reactive oxygen species at the cellular level also showed that iron porphyrin reacts with overexpressed hydrogen peroxide in the tumor microenvironment to generate more hydroxyl radicals,which has a good chemokinetic therapeutic effect;secondly,GNR@Fe TCPP-MOF After the nanomaterials were irradiated with 808 nm laser,the killing power to tumor cells was greater,and the apoptosis rate reached 79.41%within 9 minutes of illumination,reflecting the effect of photothermal synergistic enhancement of chemokinetic therapy.Then,GNR@Fe TCPP-MOF nanomaterials were applied to tumor mice.After 5 minutes of 808 nm laser irradiation at 1 W/cm²,the tumor site of the mice turned black,and scabs began to appear the next day.The volume of murine tumors approached zero,and no tumor recurrence was observed during the 14 days treatment period.It is indicated that the GNR@Fe TCPP-MOF nanomaterial has a good photothermally enhanced chemokinetic treatment effect.