Chlorine6

Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT.[Pubmed:37161611]

Biomater Res. 2023 May 9;27(1):43.

BACKGROUND: Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu(2+) that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. METHODS: A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu(2 +) into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. RESULTS: It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu(2 +) is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H(2)O overexpressed at the tumor site. CONCLUSIONS: By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.

DNAzyme-Assisted Nano-Herb Delivery System for Multiple Tumor Immune Activation.[Pubmed:36156383]

Small. 2022 Nov;18(45):e2203942.

As a promising therapeutic strategy against cancer, immunotherapy faces critical challenges, especially in solid tumors. Immune checkpoint blockade therapy, particularly blocking the interaction of the programmed cell death 1 (PD1)-PD1 ligand 1 (PD-L1) axis, can reverse the suppression of T cells so as to destroy tumor cells and exert antitumor effects. Here, a strategy of multiple activation of immune pathways is developed, to provide supporting evidence for potential antitumor therapies. Briefly, a pH/glutathione responsive drug-loading hollow-manganese dioxide (H-MnO(2) )-based Chlorine6 (Ce6)-modified DNAzyme therapeutic nanosystem for the combination of gene therapy and immunotherapy is established. The H-MnO(2) nanoparticles could efficiently deliver the DNAzyme and glycyrrhizic acid (GA) to enhance the tumor target effects. In the tumor microenvironments, the biodegradation of H-MnO(2) via pH-induced hydrolyzation allows the release of guest DNAzyme payloads and host Mn(2+) ions, which serve as PD-L1 mRNA-targeting reagent and require DNAzyme cofactors for activating gene therapy. In addition, Mn(2+) is also associated with the immune activation of thcGAS-STING pathway. Auxiliary photosensitizers Ce6 and GA could produce reactive oxygen species, resulting in immunogenic cell death. Overall, this study provides a general strategy for targeted gene inhibition and GA release, which is valuable for the development of potential tumor immunotherapies.

NIR-Triggered and ROS-Boosted Nanoplatform for Enhanced Chemo/PDT/PTT Synergistic Therapy of Sorafenib in Hepatocellular Carcinoma.[Pubmed:36125619]

Nanoscale Res Lett. 2022 Sep 20;17(1):92.

Although being the first-line treatment of advanced hepatocellular carcinoma (HCC), sorafenib (SOR) outcome is limited due to drug resistance and low tumor accumulation. Herein, with MnO(2) as photothermal agent and Chlorine6 (Ce6) as photosensitizer, a tumor-targeting and NIR-triggered multifunctional nanoplatform loading sorafenib (MnO(2)-SOR-Ce6@PDA-PEG-FA, MSCPF) was constructed. Owing to oxygen generator MnO(2), MSCPF could generate excessive ROS, thus can alleviate tumor hypoxia and improve sorafenib accumulation in cancer cells. Besides, ROS production further strengthens Ce6-mediated PDT and PDA-mediated PTT. By exploiting these features, MSCPF exhibited excellent antitumor effects on HCC in the in vitro and in vivo studies, compared to solo sorafenib or PDT/PTT treatment. Further mechanism experiments suggested that MSCPF could inhibit P-gp expression and induce ferroptosis via deactivation of GPX4 and SLC7A11, which ultimately enhanced the antitumor efficacy of SOR. In summary, our work highlights a promising NIR-triggered and ROS-boosted nanoplatform for enhanced chemo/PDT/PTT synergistic therapy of SOR in HCC treatment.