Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin
Ontology highlight
ABSTRACT:
SUBMITTER: Li Z
PROVIDER: S-EPMC10962080 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.
| S-EPMC10199622 | biostudies-literature
Project description:Atherosclerosis (AS), an inflammatory disease characterized by lipid accumulation, has a high global incidence and mortality rate. Recently, nanotherapeutic approaches that target pathological sites and improve drug bioavailability and biocompatibility hold great promise for AS treatment. In this study, a biomimetic ROS-responsive hyaluronic acid-based nanomaterial was prepared for targeted anti-AS. Specifically, a safe ROS-responsive carrier based on hyaluronic acid (HSP) was prepared to load methotrexate (MTX), a drug known for its ability to enhance lipid excretion, resulting in the formation of MTX-loaded nanoparticles (MTXNPs). Furthermore, the macrophage membrane was coated on the surface of MTXNPs to obtain MM/MTXNPs. Both MTXNPs and MM/MTXNPs exhibited ROS responsiveness and demonstrated excellent biocompatibility. In vitro experiments revealed that MM/MTXNPs could evade macrophage phagocytosis and exhibited high uptake rates by inflamed endothelial cells. MM/MTXNPs also reduced lipid accumulation in foam cells. In vivo experiments showed that MM/MTXNPs exhibited superior accumulation at AS plaque sites, facilitated by the surface membrane layer containing integrin α4β1 and CD47, resulting in an enhanced therapeutic effect in inhibiting plaque development compared to free MTX and MTXNPs. Therefore, HSP represents a promising nanocarrier to load hydrophobic MTX, enabling effective and biocompatible enhancement of AS treatment.
| S-EPMC11474234 | biostudies-literature
Project description:The role of liposomes as drug carriers has been investigated. Ultrasound-based drug release methods have been developed for on-demand drug delivery. However, the acoustic responses of current liposome carriers result in low drug release efficiency. In this study, CO2-loaded liposomes were synthesized under high pressure from supercritical CO2 and irradiated with ultrasound at 237 kHz to demonstrate their superior acoustic responsiveness. When liposomes containing fluorescent drug models were irradiated with ultrasound under acoustic pressure conditions that are safe for the human body, CO2-loaded liposomes synthesized using supercritical CO2 had 17.1 times higher release efficiency than liposomes synthesized using the conventional Bangham method. In particular, the release efficiency of CO2-loaded liposomes synthesized using supercritical CO2 and monoethanolamine was 19.8 times higher than liposomes synthesized using the conventional Bangham method. These findings on the release efficiency of acoustic-responsive liposomes suggest an alternative liposome synthesis strategy for on-demand release of drugs by ultrasound irradiation in future therapies.
| S-EPMC9958408 | biostudies-literature
Project description:High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.
| S-EPMC10026753 | biostudies-literature
Project description:Immune checkpoint blockade (ICB) therapies that target programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway are currently used for the treatment of various cancer types. However, low response rates of ICB remain the major issue and limit their applications in clinic. Here, we developed a ROS-responsive synergistic delivery system (pep-PAPM@PTX) by integrating physically-encapsulated paclitaxel (PTX) and surface-modified anti-PD-L1 peptide (pep) for combined chemotherapy and ICB therapy. Pep-PAPM@PTX could bind the cell surface PD-L1 and drive its recycling to lysosomal degradation, thus reverting PTX-induced PD-L1 upregulation and downregulating PD-L1 expression. As a result, pep-PAPM@PTX significantly promoted T cell infiltration and increased tumor immunoactivating factors, synergizing PTX chemotherapy to achieve enhanced anticancer potency in a triple-negative breast cancer (TNBC) model.
| S-EPMC9130108 | biostudies-literature
Project description:The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.
| S-EPMC8286794 | biostudies-literature
Project description:We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood-brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes.
| S-EPMC6844026 | biostudies-literature
Project description:Immunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-D, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.
| S-EPMC10018933 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) is the most lethal subtypes of breast cancer. Although chemotherapy is considered the most effective strategy for TNBC, most chemotherapeutics in current use are cytotoxic, meaning they target antiproliferative activity but do not inhibit tumor cell metastasis. Here, a TNBC-specific targeted liposomal formulation of epalrestat (EPS) and doxorubicin (DOX) with synergistic effects on both tumor cell proliferation and metastasis is described. These liposomes are biocompatible and effectively target tumor cells owing to hyaluronic acid (HA) modification on their surface. This active targeting, mediated by CD44-HA interaction, allows DOX and EPS to be delivered simultaneously to tumor cells in vivo, where they suppress not only TNBC tumor growth and the epithelial-mesenchymal transition, but also cancer stem cells, which collectively suppress tumor growth and metastasis of TNBC and may also act to prevent relapse of TNBC.
| S-EPMC11878215 | biostudies-literature
Project description:BackgroundReactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.MethodsIndocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.ResultsCompared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.ConclusionsLipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.
| S-EPMC8111982 | biostudies-literature