- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Codelivery of a cytotoxin and photosensitiser <i>via</i> a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release
摘要： Endosomal entrapment is a key issue for the intracellular delivery of many nano-sized biotherapeutics to their cytosolic or nuclear targets. Photochemical internalisation (PCI) is a novel light-based solution that can be used to trigger the endosomal escape of a range of bioactive agents into the cytosol leading to improved efficacy in pre-clinical and clinical studies. PCI typically depends upon the endolysosomal colocalisation of the bioactive agent with a suitable photosensitiser that is administered separately. In this study we demonstrate that both these components may be combined for codelivery via a novel multifunctional liposomal nanocarrier, with a corresponding increase in the biological efficacy of the encapsulated agent. As proof of concept, we show here that the cytotoxicity of the 30 kDa protein toxin, saporin, in MC28 fibrosarcoma cells is significantly enhanced when delivered via a cell penetrating peptide (CPP)-modified liposome, with the CPP additionally functionalised with a photosensitiser that is targeted to endolysosomal membranes. This innovation opens the way for the efficient delivery of a range of biotherapeutics by the PCI approach, incorporating a clinically proven liposome delivery platform and using bioorthogonal ligation chemistries to append photosensitisers and peptides of choice.
关键词： photosensitiser,codelivery,cell penetrating peptide,photochemical internalisation,saporin,liposomal nanocarrier,endosomal escape
更新于2025-11-14 15:32:45
-
Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy
摘要： Background: The existing chemo/radiotherapy fail to eliminate cancer cells due to the restriction of either drug resistance or radio tolerance. The predicament urges researchers to continuously explore alternative strategy for achieving a potent curative effect. Methods: Functional chlorin gold nanorods (Ce6-AuNR@SiO2-d-CPP) were fabricated aiming at treating breast cancer by photothermal/photodynamic therapy (PTT/PDT). The nanostructure was developed by synthesizing Au nanorods as the photothermal conversion material, and by coating the pegylated mesoporous SiO2 as the shell for entrapping photosensitizer Ce6 and for linking the D-type cell penetrating peptide (d-CPP). The function of Ce6-AuNR@SiO2-d-CPP was verified on human breast cancer MCF-7 cells and MCF-7 cells xenografts in nude mice. Results: Under combinational treatment of PTT and PDT, Ce6-AuNR@SiO2-d-CPP demonstrated a strong cytotoxicity and apoptosis inducing effects in breast cancer cells in vitro, and a robust treatment efficacy in breast cancer-bearing nude mice. The uptake mechanism involved the energy-consuming caveolin-mediated endocytosis, and Ce6-AuNR@SiO2-d-CPP in PTT/PDT mode could induce apoptosis by multiple pathways in breast cancer cells. Conclusion: Ce6-AuNR@SiO2-d-CPP demonstrated a robust efficacy in the treatment of breast cancer by photothermal/photodynamic therapy. Therefore, the present study could offer a new promising strategy to treat the refractory breast cancer.
关键词： PTT/PDT,apoptosis,cellular uptake,functional chlorin gold nanorods,cell penetrating peptide,cytotoxicity
更新于2025-09-23 15:23:52
-
Peptide and drug functionalized fluorescent quantum dots for enhanced cell internalization and bacterial debilitation
摘要： This report illustrates a strategy for designing a nanoconjugate derived vector which efficiently delivers antimicrobial drug directly into bacterial cells. The nanoconjugate comprises of negatively charged CDTe@CdS quantum dot (QD) with its surface functionalized using cationic BP-100 (KKLFKKILKYL-amide); a known cell penetrating peptide (CPP), via electrostatic approach. The interactions between QD and CPP in QDs functionalized CPPs (QD-CPP) have been well analysed using fluorescence spectroscopy, gel electrophoresis and zeta potential analysis. The QD-CPP conjugate was internalized into Gram-negative (E. coli) as well as Gram positive (S. aureus) bacterial strains with confocal studies exhibiting a strong signal in tested microorganisms. Further, to check the applicability of QD-CPP conjugate, as a delivery vector for generating an effective therapeutics, ampicillin molecules were conjugated on QD-CPP surface to generate QD-CPP-Amp conjugate. The CPP and drug molecules on the surface of QDs were well quantified using HPLC data. It was observed that the internalization and bacterial debilitation of QD-CPP-Amp conjugate is two to four fold effective as compared to bare ampicillin. The morphological changes to the bacterial cells upon the treatment with QD-CPP-Amp conjugates, were noted with no cytotoxic effect on tested mammalian cell lines. The results inferred that the proposed QD-CPP vector provides a targeted and proficient approach for cellular internalization of cargo (drug) in bacterial cells with effective tracking through florescent QDs.
关键词： antibacterial,QD-CPP conjugate,bacterial internalization,quantum dots,cell penetrating peptide
更新于2025-09-23 15:19:57
-
ZnO nanoparticles modified with an amphipathic peptide show improved photoprotection in skin
摘要： ZnO nanoparticles of different sizes were functionalized with an amphipathic peptide and its effect on nanoparticle stabilization and UV photoprotective activity was studied in this article. The peptide modified nanoparticles exhibited lower aggregation, significant reduction in Zn2+ leaching in-vitro and even inside the cells for smaller particle sizes, reduced photocatalytic activity and reduced cellular toxicity under UV-B treated conditions. In addition, the peptide modified 60 nm sized ZnO nanoparticles showed lower genotoxicity, lower oxidative stress induction levels, less DNA damage responses and less immunogenic potential than the bare counterparts in presence of UV-B rays. They localized more in the stratum corneum and epidermis ex-vivo indicating better retention in epidermis and demonstrated improved UV-B protection and/or skin integrity in SKH-1 mice in-vivo as compared to unmodified nanoparticles and commercial UV protective agents tested. To our knowledge, this is the first report on application of peptide modified ZnO nanoparticles for improved photoprotection.
关键词： UV-B rays,ZnO nanoparticles,cytotoxicity,cell penetrating peptide,photoprotection
更新于2025-09-09 09:28:46
-
Cell-Penetrating Peptides Transport Noncovalently Linked Thermally Activated Delayed Fluorescence Nanoparticles for Time-Resolved Luminescence Imaging
摘要： Luminescent probes and nanoparticles (NPs) with long excited state lifetimes are essential for time-resolved biological imaging. Generally, cell membranes are physiological barriers that could prevent the uptake of many unnatural compounds. It is still a big challenge to prepare biocompatible imaging agents with high cytomembrane permeability, especially for nonmetallic NPs with long-lived luminescence. Herein, an amphiphilic cell-penetrating peptide, F6G6(rR)3R2, was designed to transport hydrophobic fluorophores across cellular barriers. Three classical thermally activated delayed fluorescence (TADF) molecules, 4CzIPN, NAI-DPAC, and BTZ-DMAC, could self-assemble into well-dispersed NPs with F6G6(rR)3R2 in aqueous solution. These NPs showed low cytotoxicity and could penetrate membranes easily. Moreover, long-lived TADF enabled them to be used in time-resolved luminescence imaging in oxygenic environments. These findings greatly expanded the applications of cell-penetrating peptides for delivery of molecules and NPs by only noncovalent interactions, which were more flexible and easier than covalent modifications.
关键词： cell-penetrating peptide,Luminescent probes,time-resolved biological imaging,nanoparticles,noncovalent interactions,thermally activated delayed fluorescence
更新于2025-09-04 15:30:14