Construction And Application In Tumor Photodynamic Therapy Of Cascade-Reactive Porphyrin MOFs

Cancer has been one of the major diseases that threaten human health and is a major public health problem worldwide.For example,in China,cancer is one of the main causes of clinical death.At present,the treatment of cancer mainly includes surgical treatment,radiotherapy and chemotherapy.However,these methods often fail to meet the clinical needs for cancer treatment due to poor treatment effect,high risk of recurrence,and large side effects.In recent years,the application of photodynamic therapy(PDT)in the treatment of solid tumors has attracted extensive attention.It is an emerging cancer treatment method that mainly relies on non-toxic photosensitizers to stimulate oxygen into reactive oxygen species that can kill tumor cells,thereby achieving anti-tumor effects.Due to the hypoxic nature of the tumor microenvironment,the source of oxygen has been the main reason for affecting the therapeutic effect of PDT.In this paper,we design and synthesize a cascade-reactive multi-functional nano-platform,which can promote the generation of oxygen through the cascade reaction and further enhance the PDT effect.In this system,porphyrin MOFs(TCPP-UiO-66-NH2,TU)containing photosensitizer(TCPP)were first prepared.TU is a spherical nanoparticle with a uniform shape and a diameter(?35 nm);then using TU as the core,a one-pot method was used to modify polydopamine(PDA)and Ca O2 NPs on its surface to obtain TUPC NPs;finally,by Na BH4 reduction method loads Pt NPs on the surface of TUPC NPs to obtain the final nanoplatform TUPCP NPs.After injecting tail vein into the constructed mouse colon cancer subcutaneous transplantation tumor model,the nanoplatform can be effectively enriched into tumor tissue through high permeability and retention(EPR)effects.The Ca O2 NPs in the nanoplatform can then react with the water in the tumor microenvironment to generate Ca(OH)2 and H2O2;the generated H2O2 can gradually decompose under the action of Pt NPs to generate oxygen,thereby improving tumor hypoxia environment;under the irradiation of laser,TCPP in the framework of MOFs can effectively activate the surrounding oxygen molecules to generate highly toxic reactive oxygen species,thereby killing tumor cells and inhibiting tumor growth.In this paper,the nanoparticles were characterized in terms of composition,morphology,particle size,etc.,and their oxygen and reactive oxygen generation capabilities were measured.The results show that the nanoparticles can effectively promote the generation of oxygen and active oxygen through the cascade-reaction.In addition,we selected mouse colon cancer cells(CT26)for bioactivity evaluation.Cell uptake experiments show that TUPCP NPs mainly enter cells by endocytosis and have good cell uptake capacity(TUPCP NPs uptake is 5 times that of TUP NPs),which is a prerequisite for PDT;The experimental results of intracellular reactive oxygen species generation also indicate that TUPCP NPs can effectively promote the generation of reactive oxygen species in tumor cells;The results of cell proliferation inhibition experiments show that the cascade reaction of Ca O2 NPs and Pt NPs in the nanoplatform promotes the generation of oxygen,which makes TUPCP NPs produce more active oxygen under 650 nm laser irradiation The cytotoxicity of tumor cells(the cell suppression rate is up to 70%)further proves that TUPCP NPs can enter the cells and improve tumor treatment effect by alleviating tumor cell hypoxia and promoting the production of reactive oxygen species;The results of in vivo anti-tumor experiments showed that TUPCP NPs showed better anti-tumor activity(tumor inhibition rate of 70%)and biological safety compared with TUP NPs that were not modified by Ca O2 NPs and Pt NPs.All in all,the multi-functional nano-platforms of cascade-reactive porphyrin MOFs that we designed have good application potential in alleviating tumor hypoxia and improving tumor photodynamic therapy effect.