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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
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Photoactivatable Prodrug-Backboned Polymeric Nanoparticles for Efficient Light-Controlled Gene Delivery and Synergistic Treatment of Platinum-Resistant Ovarian Cancer
摘要： Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, lacking of suitable co-delivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. Herein, we developed a photoactivatable Pt(IV) prodrug-backboned polymeric nanoparticles system (CNPPtCP/si(c-fos)) for light-controlled si(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNAi on platinum-resistant ovarian cancer (PROC). Upon blue light irradiation (430 nm), CNPPtCP/si(c-fos) could generate oxygen-independent N3? with mild oxidation energy for efficient endo/lysosomal escape through N3?-assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt(IV) prodrug activation, CNPPtCP/si(c-fos) would be disassociated to release active Pt(II) and unpack si(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNPPtCP/si(c-fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug co-delivery tactics for treatment of various hard-to-tackle cancers.
关键词： N3?-assisted photochemical internalization,photoactivatable polymeric nanoparticles,gene delivery,platinum-resistant ovarian cancer,photoactivated chemotherapy
更新于2025-09-19 17:13:59
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The luminescent HiBiT peptide enables selective quantitation of G proteina??coupled receptor ligand engagement and internalization in living cells
摘要： G protein– coupled receptors (GPCRs) are prominent targets to new therapeutics for a range of diseases. Comprehensive assessments of their cellular interactions with bioactive compounds, particularly in a kinetic format, are imperative to the development of drugs with improved efficacy. Hence, we developed complementary cellular assays that enable equilibrium and real-time analyses of GPCR ligand engagement and consequent activation, measured as receptor internalization. These assays utilize GPCRs genetically fused to an N-terminal HiBiT peptide (1.3 kDa), which produces bright luminescence upon high-affinity complementation with LgBiT, an 18-kDa subunit derived from NanoLuc. The cell impermeability of LgBiT limits signal detection to the cell surface and enables measurements of ligand-induced internalization through changes in cell-surface receptor density. In addition, bioluminescent resonance energy transfer is used to quantify dynamic interactions between ligands and their cognate HiBiT-tagged GPCRs through competitive binding with fluorescent tracers. The sensitivity and dynamic range of these assays benefit from the specificity of bioluminescent resonance energy transfer and the high signal intensity of HiBiT/LgBiT without background luminescence from receptors present in intracellular compartments. These features allow analyses of challenging interactions having low selectivity or affinity and enable studies using endogenously tagged receptors. Using the (cid:2)-adrenergic receptor family as a model, we demonstrate the versatility of these assays by utilizing the same HiBiT construct in analyses of multiple aspects of GPCR pharmacology. We anticipate that this combination of target engagement and proximal functional readout will prove useful to the study of other GPCR families and the development of new therapeutics.
关键词： LgBiT,receptor internalization,BRET,ligand engagement,NanoLuc,HiBiT,GPCR,bioluminescent resonance energy transfer
更新于2025-09-19 17:13:59
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Wrinkled metal based quantum sensor for In vitro cancer diagnosis
摘要： This article presents a unique 3D biocompatible Aluminum-based quantum structure (QS) for in vitro cancer detection using Surface Enhanced Raman Scattering (SERS). The Al-based QSs fabricated using ultrashort pulsed laser are of two distinct surface characters, wrinkled and smooth spherical. The limit of detection for chemical sensing of Crystal Violet and Rhodamine 6G by the Al-QS was driven up to single molecule sensing (femtomolar concentration). Biological sensing of cysteine, a disease biomarker and carcinoembryonic antigen (CEA), a cancer biomarker was also tested by the Al-QS. The ability of in vitro cell detection using Al-QS was analyzed with three cell lines, mammalian fibroblast and pancreatic and lung cancer cells. The Al-QS were up taken by the cells through label-free self-internalization and were sensed by SERS. Further assay was performed to differentiate cancerous and non-cancerous cells by measuring lipid and protein peak intensity within the cells. The result of this research indicated that SERS based Al-QS could be a suitable candidate for the early diagnosis of cancer.
关键词： SERS,self-internalization,invitro cancer diagnosis,single molecule sensing,metallic quantum probe
更新于2025-09-12 10:27:22
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Differences between Neutrophilic Granulocytes and Lymphocytes in Fixation of Quantum Dots of Different Composition
摘要： Studies by flow cytometry, scanning electron microscopy, and X-ray microanalysis have shown that fixation/internalization of quantum dots differ in lymphocytes and neutrophilic granulocytes. Punctate fixation of quantum dots to cell surface is characteristic of lymphocytes, while phagocytosis with perinuclear location of quantum dot aggregations is characteristic of neutrophils. The presence of complex functional groups on the surface of quantum dots can inhibit significantly the fixation/internalization of quantum dots by blood cells.
关键词： lymphocytes,neutrophilic granulocytes,internalization,quantum dots,phagocytosis
更新于2025-09-11 14:15:04
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Interfacial uploading of luminescent hexamolybdenum cluster units onto amino-decorated silica nanoparticles as new design of nanomaterial for cellular imaging and photodynamic therapy
摘要： The present work introduces a facile synthetic route to embed phosphorescent K2[{Mo6I8}I6] and (nBu4N)2[{Mo6I8}(CH3COO)6] clusters (C) onto silica-water interface of amino-decorated silica nanoparticles (SNs, 60±6 nm). The assembled C-SNs gain in the luminescence intensity, which remains stable within three months after their assembly. High uptake capacity of the clusters (8700 of K2[{Mo6I8}I6] and 6500 of (nBu4N)2[{Mo6I8}(CH3COO)6] per the each nanoparticle) derives from ionic self-assembly and coordination bonds between the cluster complexes and ionic (amino- and siloxy-) groups at the silica surface. The coordination via amino- or siloxy-groups restricts aquation and hydrolysis of the embedded clusters, in comparison with the parent K2[{Mo6I8}I6] and (nBu4N)2[{Mo6I8}(CH3COO)6. High potential of the assembled nanoparticles in the ROS generation was revealed by EPR measurements facilitated by spin trapping. The high positive charge and convenient colloid stability of the assembled C-SNs hybrids are the prerequisite for their efficient cellular uptake, which is exemplified in the work by MCF-7 cell line. The measured dark and photoinduced cytotoxicity of the C-SNs hybrids reveals significant photodynamic therapy effect on the MCF-7 cancer cell line versus the normal cells. This effect is entirely due to the embedded clusters and is dependent on the chemical composition of the cluster.
关键词： hexamolybdenum cluster,adsorption,silica nanoparticles,cell internalization,photodynamic therapy,luminescence
更新于2025-09-10 09:29:36