Anti-solid Tumor Effects Of Nanodiamonds And Responsive Nano Materials

Tumors can be classified into solid tumors and non-solid tumors.Solid tumors can be detected as visible masses.Non-solid tumors are mainly hematopoietic tumors,accounting for only 10% of all tumors,and cannot be detected by imaging examination.At present,the studies of nanomaterials mainly focus on the diagnosis and treatment of tumors solid tumors and have made great progress in this area.In our earlier study,we found that nano-diamond(NDs)combined with arsenic trioxide(ATO)significantly improved the treatment efficiency of ATO in solid tumors in the treatment of liver cancer,and NDs significantly blocked autophagy.Based on this phenomenon,this paper analyzes the mechanism that leads to the result.The responsive NIR-II nanoprobe has the advantages of tumor specificity and NIR-II fluorescence and has great potential for clinical application in tumor imaging and treatment.The feasibility and safety of the new probes at the cellular and animal levels are the focus of probe development.Therefore,this paper studied the mechanism of NDs blocking autophagy and the application of the newly developed responsive nano fluorescent probe NIR-II@Si(Second near-infrared window core-shell silica nanocomposites)and responsive nano photothermal probe Nano-PT(Nanostructured photothermal agent)in tumor imaging and photothermal therapy.The main research results are summarized as follows:(1)The detection of Western Blot(WB)showed that NDs could cause the aggregation of LC3 and P62 in cells,indicating that NDs had a regulatory effect on autophagy flow and the detection of tandem reporter gene mCherry-GFP-LC3 that distinguished the processing dysfunction of autolytic lysosome showed that NDs,as an autophagy inhibitor,mainly acts by regulating autophagy flow and autophagy content flow.The detection of the target sites of NDs in cells revealed that the expression of Nuclear protein-1(NUPR1)in cells was negatively correlated with the incubation time of NDs.After incubation with NDs,Synaptosome-associated protein 25(SNAP-25),and Vesicle-associated membrane protein 8(VAMP8),the downstream genes of NUPR1,decrease expression correspondingly.SNAP25 and VAMP8 involved in the autolysosomal efflux in cells.Then,the expression of autophagy-related proteins 5(ATG5)and autophagy-related proteins 7(ATG7)were successfully knocked out by interfering RNA,which inhibited the occurrence of autophagy in the upstream.We found that the regulation effect of NDs on NUPR1 expression disappeared after ATG5 and ATG7 were knocked out,and the tumor inhibition effect of NDs/ATO co-treatment was significantly reduced.The results indicated that NDs blocked autophagy by controlling the expression of NUPR1 in cells during the treatment,which improved the therapeutic effect of ATO for solid tumors.(2)We evaluated the distribution,metabolism,and biocompatibility of NDs and NDs/ATO co-treatment.Firstly,in the process of NDs/ATO co-treatment,NDs and ATO are distributed in the whole body,but the drugs are more concentrated in the tumor,and the NDs and ATO will be expelled from the body rapidly after the administration cycle.Secondly,we found that NDs had no significant side effects on hematological blood biochemical indexes during drug administration.Thirdly,the liver tissue was not damaged during administration,but the lesions caused by the tumor had a certain recovery.Finally,the NDs/ATO co-treatment did not significantly affect body weight.Therefore,NDs/ATO co-treatment is a safe method and has the potential for clinical application.(3)NIR@Si was used to detect the imaging effect in vitro and in vivo respectively,and compared with the imaging effect in NIR-I.The results showed that NIR@Si had high cancer specificity,high imaging resolution,and high penetration depth of tissue.At the individual level,the imaging effect can be artificially controlled by controlling the contents of corresponding substrates.The biocompatibility of NIR@Si was tested,and the results showed that this probe could be quickly distributed to the main organs and quickly discharged from the body,and had no significant side effect on hematological,biochemistry indexes.Therefore,NIR@Si has a high imaging resolution,excellent biocompatibility,and clinical application potential.(4)The photothermal therapeutic effect of Nano-PT was detected in vitro and in vivo.The results showed that Nano-PT had high cancer specificity,high photothermal conversion efficiency and improvement of therapeutic efficacy.The biocompatibility of Nano-PT was tested,and the results showed that the probe had no significant effect on major organs and adjacent tissues of the tumor,and had no significant side effect on blood biochemistry.Therefore,Nano-PT has a high photothermal conversion efficiency,excellent biocompatibility,and great clinical application potential in the treatment of colon cancer.In conclusion,we studied the phenomenon of NDs/ATO co-treatment of solid tumor,explained the reason that NDs improves ATO treatment of solid tumors by blocking autophagy,found the target of NDs blocking autophagy,discussed the safety of NDs/ATO co-treatment of solid tumor,provided theoretical support for the feasibility of NDs/ATO co-treatment of solid tumor.Then,the tumor imaging effect of the newly developed tumor responsive nano fluorescent probe NIR@Si and the photothermal treatment effect of nano photothermal Nano-PT were detected.The experimental results showed that the two kinds of probes were high cancer specificity,and the tumor imaging and treatment were achieved respectively.The two new probes have excellent biocompatibility and clinical application potential.