Construction Of Precise Controlled Release Carrier Based On Prussian Blue/10-hydroxycamptothecin And Study Of Its Anti-tumor Effec

With the development of science and technology,the treatment strategies of cancer have gradually become diversified,and various nanomaterials with unique physical and chemical properties have emerged rapidly in the biomedical field,which has avoided the disadvantages of traditional cancer treatment methods to a certain extent.A series of stimulus-responsive drug carriers(p H response,redox response,photoresponse,enzyme response)have been developed successively.Under the stimulation of the external environment,the drug can achieve accurate release and accurate treatment at the tumor site,greatly reducing the toxic side effects on normal tissues.In this paper,according to the tumor microenvironment(TME),we designed the drug carriers with near-infrared light response and reactive oxygen species(ROS)response,which can realize multiple therapy.(1)Tumor cells rely on nutrients transported by nearby blood vessels to survive,so when the blood vessels are embolized,the tumor cells will starve to death.This "starvation therapy" is a very reliable treatment with low risk coefficient and good treatment effect.Prussian blue(PB)is a kind of nanometer material with low toxicity,easy synthesis and good photothermal effect.In this paper,the Prussian blue nano-cage(PB Cage)obtained after etching of PB was used as the carrier of Thr,and the Thr was encapsulated in PB Cage with phase change material(PCM)lauric acid to obtain(Thr/PCM)@PB Cage with a diameter of about 160 nm.The drug delivery system effectively avoids the pre-leakage of Thr and can accumulate at the tumor site.Under the irradiation of near infrared light,PB Cage with photothermal effect can rapidly heat up(above 45 ℃),providing a heat source for photothermal treatment and PCM melting,so that Thr can be accurately released at the tumor site,and thus realize the synergistic treatment of photothermal therapy and starvation therapy.It can be seen from biological experiments that(Thr/PCM)@PB Cage has better controllability and therapeutic effectiveness than single therapy.Photothermal therapy combined with starvation therapy is a relatively novel tumor treatment scheme.(2)The presence of abnormal metabolic conditions makes tumor cells have a high content of ROS,which can also be used to construct ROS responsive drug carriers.After the reaction of 10-hydroxycamptothecin(HCPT)with a ROS responsive thioketol linker,a polymeric prodrug(keto-)p HCPT was formed,and then a hydrophilic polymer(keto-)p HCPT-PEI was synthesized by connecting polyvinylimine(PEI)at both ends.This polymer can self-assemble into a 110 nm particle size micelle in water,and the positively charged PEI can be complex with the negatively charged p DNA,which allows the drug carrier to deliver the HCPT at the same time as the p DNA.The drug carriers can be rapidly ruptured in oxidizing/reducing environments,resulting in the release of HCPT and p DNA,thus enabling the combination of chemotherapy and gene therapy.In vitro experiments also showed that the drug delivery system had better efficacy than a single drug,which laid the foundation and paved the way for subsequent in vivo experiments.The system is expected to achieve good results in vivo efficacy verification.Finally,the drug delivery system based on PB/HCPT constructed in this paper can achieve efficient accumulation and precise release of drugs at the tumor site,and realize the combined action of multiple treatment modalities,greatly improving the efficiency of tumor treatment.