This study focuses on the role of chlorophyll, the Folium Apocyni herbal medicine, and Rhizoma polygonati sugar carbon dots in developing carbon dioxide biosensors. The experimental approach focuses on evaluating fluorescence intensity, phosphatase activity, and surface effects as potential detection mechanisms. The observed changes highlight their potential applicability in creating effective and reliable biosensors.

Poly(ADP-ribose) polymerase-1 (PARP) inhibitors have been applied in BRCA-mutated cancers including ovarian, breast and prostate cancers. However, drug resistance may develop by multiple mechanisms. Nanotechnology has advanced drug delivery and reduced drug resistance, but some nano carriers have toxicity, such as carbon dots. Here we report a light controllable drug delivery to cancer cells by chlorophyll forming a selfembedded complex of carbon nanoparticles including PARP inhibitor olaparib, and deer antler extract (4mix). The light and dark pretreatment were performed with regular light for 6 h and wrapping by foil as dark control respectively. We found light disrupted the compact assembly structure and enhanced the phosphatase nanozyme activity of 4-mix. For cell studies, normal lung cell MRC-5 as control, lung cancer cell A549 was used for comparative analysis. Consistent with the changes in structure, though 6 h regular light treatment reduced the cytotoxicity in lung cancer A549 cells, overall dark enhanced the efficiency of 4-mix compared with olaparib alone by more than three-fold (20% cell viability vs 65% viability). The above effect is counteracting in the normal lung cell line of MRC-5 suggesting the cancer associated controllable cytotoxicity effect. Thus, light controlled drug delivery may reduce side effects of cytotoxicity of carbon dots materials. Most importantly, we provided insights of light controlled drug response for reducing side effects of nano carriers for potent tumor spatial delivery by green sustainable materials from natural products to target PARP, an important drug target in cancer therapy.

Excessive carbon emissions, especially CO2 release, have been a global concern. Few studies applied nanotechnology to relieve the ecotoxicity of CO2. Here, we applied carbon dots (CDs) to neutralize the CO2. We found CO2 induced the aggregation of CDs, which is of significance for CDs in enhanced fluorescence intensity but decreased CDs function in nanozyme activity, and reduced CDs toxicity to bacteria and cancer cells. Our data suggest the concern of CO2 release in global health in CDs mediated anticancer drug delivery and antibiotics resistance. However, enhanced fluorescence in cells which can be applied for bioimaging or CO2 sensing as simulated investigation by static charged attraction of positively charged CDs with negatively charged soluble HCO3-. Thus, CO2 abrogates the nanomedicine efficacy in cancer cells and antibacterial and may induce drug resistance for patients undergoing chemotherapy or antibiotics therapy. To overcome the resistance, we may apply the CDs for a neutralization of CO2 for impact on anticancer nanomedicine and antibiotics and reducing the ecotoxicity in biological systems.

Baked cysteine is mainly composed of cystine, a dimer with a SS bond. It acts as a nanozyme with phosphatase activity and an allosteric mechanism, repairs damage caused by ash to plant roots and germination and synergically combines with chlorophyll.

Deer antler extract contains chemical compounds and peptides which have been shown to exert many pharmacological functions. However, the extract may also exhibits potential particle characteristics at nanoscale thereby acting as intrinsic nanozyme upon processing. We aim to test the nanoscale effect on cancer cells. We found that the water extract contains nanoscale particles characterized by SEM, TEM, AFM, zeta potential, and exhibits nanozyme or co-nanozyme activities of phosphatase, catalase which has crosstalk associated with anti-prostate cancer cells viability, especially with combined inhibitor of MET kinase by co-targeting phosphorylation. Network pharmacology analysis also showed immune mechanisms. Docking analysis shows the potent antler extract compound mediated inhibition of MET kinase. Nanoscale particles and compounds from antler extract at least in part, contribute to anticancer mechanisms which would be a promising combination agent in anti-cancer via nanotechnology.

Background: Phosphatase has been well studied in anti-cancer research. The dietary amino acid cysteine plays essential roles in protein structure by disulfide bonds, metal ion binding, detoxification, and many metabolic functions. Cysteine has been shown in inducing human bladder cancer cells apoptosis. However, the cysteine mediated nanoparticles enzyme (nanozyme) activity and their function, signaling pathways are yet unknown. We aim to test whether the cysteine mediated nanoparticles nanozyme activity of phosphatase could enhance targeting of kinases. Methods: Fresh L-cysteine were applied for synthesis of less than 200 nm sized nanozyme. The phosphatase enzyme activity was measured using NBT/BCIP substrate. Scanning electron microscopy, transmission electron microscopy were used for nanoparticle analysis. Cell viability was measured by crystal violet staining of cells. Results: L-cysteine at 0.1mg/mL combined with MET inhibitor (1µm or 5µm) showed the better effect of enhanced efficacy and decreased the viability of prostate cancer cells compared to inhibitor alone or cysteine. Combination did not affect the phosphatase activity of cysteine nanozyme. Conclusion: L-cysteine may be applied to be combined with kinase inhibitors in drug delivery for increased efficacy. Citation Format: Arailym Myrzagaliyeva, Guldan Nazarbek, Sandugash Myrzagali, Amr Amin, Yingqiu Xie. Phosphatase nanozyme combination with kinase inhibitor for decreasing prostate cancer cell viability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2556.

Honghua (Carthami flos) and Xihonghua (Croci stigma) have been used in anti-COVID-19 as Traditional Chinese Medicine, but the mechanism is unclear. In this study, we applied network pharmacology by analysis of active compounds and compound-targets networks, enzyme kinetics assay, signaling pathway analysis and investigated the potential mechanisms of anti-COVID-19. We found that both herbs act on signaling including kinases, response to inflammation and virus. Moreover, crocin likely has an antiviral effect due to its high affinity towards the human ACE2 receptor by simulation. The extract of Honghua and Xihonghua exhibited nanozyme/herbzyme activity of alkaline phosphatase, with distinct fluorescence. Thus, our data suggest the great potential of Honghua in the development of anti-COVID-19 agents.

Nanozymes and natural product-derived herbzymes have been identified in different types of enzymes simulating the natural protein-based enzyme function. How to explore and predict enzyme types of novel nanozymes when synthesized remains elusive. An informed analysis might be useful for the prediction. Here, we applied a protein-evolution analysis method to predict novel types of enzymes with experimental validation. First, reported nanozymes were analyzed by chemical classification and nano-evolution. We found that nanozymes are predominantly classified as protein-based EC1 oxidoreductase. In comparison, we analyzed the evolution of protein-based natural enzymes by a phylogenetic tree and the most conserved enzymes were found to be peroxidase and lyase. Therefore, the natural products of Rhizoma polygonati and Goji herbs were analyzed to explore and test the potent new types of natural nanozymes/herbzymes using the simplicity simulation of natural protein enzyme evolution as they contain these conserved enzyme types. The experimental validation showed that the natural products from the total extract of nanoscale traditional Chinese medicine Huangjing (RP, Rhizoma polygonati) from Mount-Tai (Taishan) exhibit fructose-bisphosphate aldolase of lyase while nanoscale Goji (Lycium chinense) extract exhibits peroxidase activities. Thus, the bioinformatics analysis would provide an additional tool for the virtual discovery of natural product nanozymes.

Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.