PEG-modified carbon-based nanoparticles as tumor-targeted drug delivery system reducing doxorubicin-induced cardiotoxicity.

Herein, a doxorubicin-loaded carbon-based drug delivery system, denoted as PC-DOX, composed of pH-responsive imine bond was developed for the tumor-targeted treatment. PC-DOX with a uniform particle size around 180 nm was synthesized by coating of as-synthesized hollow carbon-based nanoparticles (NPs) with dialdehyde PEG, which was used as carrier to attach DOX covalently through dynamic covalent bond. The unique structure endowed the advantages of specific tumor targeting and tumor microenvironment (TME) specific drug delivery capacity with PC-DOX. For the one hand, the tumor targeting caused by the enhanced permeability and retention (EPR) effect could significantly improve the tumor cellular uptake. For the other hand, the pH-responsiveness could realize the effective DOX accumulation in tumor tissues, avoiding the unwanted side effect to the normal tissues. As a result, PC-DOX with high DOX loading capacity (70.12%) and excellent biocompatibility, concurrently, presented a significant anti-tumor effect at a low mass concentration (DOX equivalent dose: 20 µg/mL). Another attractive characteristic of PC-DOX was the remarkable protective effect towards DOX-induced cardiotoxicity, which could be clearly observed from in vitro cellular, and animal assays. Compared with free DOX, the cardiomyocyte viability increased by average 30.58%, and the heart function was also significantly improved. This novel drug delivery nanoplatform provides a new method for the future clinical application of DOX in the cancer's therapeutics.

Biodegradable porous polymeric drug as a drug delivery system: alleviation of doxorubicin-induced cardiotoxicity via passive targeted release.

Doxorubicin (DOX) is an effective chemotherapeutic drug developed against a broad range of cancers, and its clinical applications are greatly restricted by the side effects of severe cardiotoxicity during tumour treatment. Herein, the DOX-loaded biodegradable porous polymeric drug, namely, Fc-Ma-DOX, which was stable in the circulation, but easy to compose in the acidic medium, was used as the drug delivery system avoiding the indiscriminate release of DOX. Fc-Ma was constructed via the copolymerization of 1,1'-ferrocenecarbaldehyde with d-mannitol (Ma) through the pH-sensitive acetal bonds. Echocardiography, biochemical parameters, pathological examination, and western blot results showed that DOX treatment caused increased myocardial injury and oxidative stress damage. In contrast, treatment with Fc-Ma-DOX significantly reduced myocardial injury and oxidative stress by DOX treatment. Notably, in the Fc-Ma-DOX treatment group, we observed a significant decrease in the uptake of DOX by H9C2 cells and a significant decrease in reactive oxygen species (ROS) production.

Utilizing Network Pharmacology and Molecular Docking Integrated Surface Plasmon Resonance Technology to Investigate the Potential Targets and Mechanisms of Tripterygium wilfordii against Pulmonary Artery Hypertension.

Background: Pulmonary artery hypertension (PAH) is a rare, life-limiting cardiopulmonary disorder characterized by the progressive and remodeling of pulmonary vasculature. Although the development of the technology brings us many approaches for the treatment of PAH, the effect of treatment is unsatisfactory. Tripterygium wilfordii (TW), as a traditional Chinese medicine (TCM), has been widely used in anti-inflammation, anticancer, and other fields. However, the potential of TW in treating PAH is currently unclear. Methods: Active ingredients and their corresponding genes were harvested from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), CTD, and STITCH. Meanwhile, genes associated with PAH were adopted from OMIM and GeneCards databases. Through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses, potential targeting KEGG pathways and functions were further collected. Then, STRING was used to generate the protein-protein interaction (PPI) network. The "ingredients-targets-pathway" network was built by Cystoscope. Finally, the binding between active ingredients of TW and corresponding targets of PAH was identified via molecular docking technology and surface plasmon resonance (SPR) experiments. Results: The network pharmacology analysis revealed 36 active ingredients in TW and 150 potential targets related to the treatment of PAH with TW. Moreover, GO enrichment analysis showed that the key function in molecular function (MF) was related to enzyme binding, the key function in biological process (BP) was related to cellular response to organic substance, and the key function in cellular component (CC) was related to KEGG enrichment analysis and found that it was closely related to the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and apoptosis. At last, molecular docking results revealed that the main active ingredients of TW had a strong binding ability with the PAH target protein. In addition, the SPR experiment revealed that kaempferol was combined with the CASP3 protein rather than PARP1, while triptolide was combined with PARP1 rather than the CASP3 protein. Conclusion: TW may have therapeutic effects on PAH through multitargets and multimethods, which provide a scientific basis for further elaborating the mechanism of Tripterygium wilfordii in the treatment of PAH.