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Screening of two-photon activated photodynamic therapy sensitizers using a 3D osteosarcoma model
摘要： Photodynamic therapy (PDT) involves a photosensitizing agent activated with light to induce cell death. Two-photon excited PDT (TPE-PDT) offers numerous benefits compared to traditional one-photon induced PDT, including an increased penetration depth and precision. However, the in vitro profiling and comparison of two-photon photosensitizers (PS) are still troublesome. Herein, we report the development of an in vitro screening platform of TPE-PS using a 3D osteosarcoma cell culture. The platform was tested using three different two-photon (2P) active compounds – a 2P sensitizer P2CK, a fluorescent dye Eosin Y, and a porphyrin derivative (TPP). Their 2P absorption cross-sections (σ2PA) were characterised using a fully automated z-scan setup. TPP exhibited a remarkably high σ2PA at 720 nm (8865 GM) and P2CK presented a high absorption at 850 nm (405 GM), while Eosin Y had the lowest 2P absorption at the studied wavelengths (<100 GM). The cellular uptake of PS visualized using confocal laser scanning microscopy showed that both TPP and P2CK were internalized by the cells, while Eosin Y stayed mainly in the surrounding media. The efficiency of the former two TPE-PS was quantified using the PrestoBlue metabolic assay, showing a significant reduction in cell viability after two-photon irradiation. The possibility of damage localization was demonstrated using a co-culture of adipose derived stem cells together with osteosarcoma spheroids showing no signs of damage to the surrounding healthy cells after TPE-PDT.
关键词： two-photon excited photodynamic therapy,PrestoBlue assay,photosensitizers,cellular uptake,localized damage,z-scan,3D osteosarcoma model
更新于2025-11-21 11:08:12
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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
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Photothermal Ablation of Cancer Cells by Albumin-Modified Gold Nanorods and Activation of Dendritic Cells
摘要： Nanoparticle-mediated photothermal therapy has been widely studied for cancer treatment. It is important to disclose how photothermally ablated tumor cells trigger immune responses. In this study, bovine serum albumin (BSA)-coated gold nanorods (BSA-coated AuNRs) were prepared and used for photothermal ablation of breast tumor cells. The BSA-coated AuNRs showed high photothermal conversion efficiency and good photothermal ablation effect towards tumor cells. The ablated tumor cells were co-cultured with immature dendritic cells (DCs) through a direct cell contacting model and diffusion model to confirm the stimulatory effects of cell–cell interaction and soluble factors released from ablated tumor cells. The results indicated that photothermally ablated tumor cells induced immune-stimulatory responses of DCs through both cell–cell interaction and soluble factors. The results should be useful for synergistic photothermal-immunotherapy of primary and metastatic cancer.
关键词： gold nanorods,cellular uptake,photothermal ablation,cancer therapy,photothermal therapy,immune responses
更新于2025-09-23 15:22:29
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Luminescent silica mesoparticles for protein transduction
摘要： Unlike silica nanoparticles, the potential of silica mesoparticles (SMPs) (i.e. particles of submicron size) for biological applications in particular the in vitro (let alone in vivo) cellular delivery of biological cargo has so far not been sufficiently studied. Here we examine the potential of luminescent (namely, octahedral molybdenum cluster doped) SMPs synthesised by a simple one-pot reaction for the labelling of cells and for protein transduction into larynx carcinoma (Hep-2) cells using GFP as a model protein. Our data demonstrates that the SMPs internalise into the cells within half an hour. This results in cells that detectably luminesce via conventional methods. In addition, the particles are non-toxic both in darkness and upon photo-irradiation. The SMPs were modified to allow their functionalisation by a protein, which then delivered the protein (GFP) efficiently into the cells. Thus, the luminescent SMPs offer a cheap and trackable alternative to existing materials for cellular internalisation of proteins, such as the HIV TAT protein and commercial protein delivery agents (e.g. Pierce?).
关键词： protein transduction,cytotoxicity,silica,Octahedral molybdenum cluster,cellular uptake
更新于2025-09-23 15:21:21
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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
摘要： The use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that a unique combination of nanocrystals core components (Ag-In-Zn-S) would eliminate the toxicity problem and increase their biomedical applications. The alloyed quaternary nanocrystals Ag-In-Zn-S (QDgreen, Ag1.0In1.2Zn5.6S9.4; QDred, Ag1.0In1.0Zn1.0S3.5) were used to transport new unsymmetrical bisacridine derivatives (UAs, C-2028 and C-2045) into lung H460 and colon HCT116 cancer cells for improving the cytotoxic and antitumor action of these compounds. UAs were coupled with QD through physical adsorption. The obtained results clearly indicate that the synthesized nanoconjugates exhibited higher cytotoxic activity than unbound compounds, especially toward lung H460 cancer cells. Importantly, unsymmetrical bisacridines noncovalently attached to QD strongly protect normal cells from the drug action. It is worth pointing out that QDgreen or QDred without UAs did not influence the growth of cancer and normal cells, which is consistent with in vivo results. In noncellular systems, at pH 5.5 and 4.0, which relates to the conditions of endosomes and lysosomes, the UAs were released from QD-UAs nanoconjugates. An increase of total lysosomes content was observed in H460 cells treated with QDs-UAs which can affect the release of the UAs from the conjugates. Moreover, confocal laser scanning microscopy analyses revealed that QD-UAs nanoconjugates enter H460 cells more efficiently than to HCT116 and normal cells, which may be the reason for their higher cytotoxicity against lung cancer. Summarizing, the noncovalent attachment of UAs to QDs increases the therapeutic efficiency of UAs by improving cytotoxicity toward lung H460 cancer cells and having protecting effects on normal cells.
关键词： lung and colon cancer cells,unsymmetrical bisacridine derivatives,drug-carrier degradation pathway,pH-dependent release,cellular uptake,in vivo antitumor efficacy,Ag-In-Zn-S nanocrystals,cytotoxic activity
更新于2025-09-23 15:21:01
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Further Development of Near-Infrared Mediated Quantum Dots and Paclitaxel Co-loaded Nanostructured Lipid Carrier System for Cancer Theragnostic
摘要： Of colloidal systems, ceteris paribus, nanostructured lipid carriers are second to none in offering a single-unit platform for multifunctional benefits. Quantum dots are known to possess unique properties that make them ideal for imaging purpose and that they may be used for cancer detection. For several decades, paclitaxel has been the most effective drug against a wide range of solid tumours. Theragnostic nanomedicine provides a platform to monitor, evaluate, and individualize treatment in real time. Evaluation of cancer treatment outcome at an early stage therapy is key to increase survival prospects of a patient. Previously, a novel co-loaded nanostructured lipid carriers’ theragnostic system for parenteral administration was developed. The aim of this study was to further investigate the co-loaded nanostructured lipid carriers in order to provide interpretation necessary for preclinical elucidation of the formulation, in part. The co-loaded nanostructured lipid carriers were prepared by oil/water emulsification-solvent evaporation technique. In this study, stability and co-loaded nanostructured lipid carriers’ internalization by MCF 7 and HepG2 cells were investigated. The co-loaded nanostructured lipid carriers was stable at 4(cid:2)C for 1 month. The formulation was successfully internalized by MCF-7 and HepG2 cells. Nevertheless, the co-loaded nanostructured lipid carrier was more apt for MCF-7 cells. This finding affirms the formulation to be the most appropriate for breast cancer treatment. In addition, if taken correctly by a patient for a month, the formulation would give true reflection of the contents’ amounts, the factor paramount to appropriate changes in treatment protocol. It can therefore safely be concluded that the co-loaded nanostructured lipid carrier formulation may be potentially an effective theragnostic translational system.
关键词： translational system,cellular uptake,theragnostic,stability study,co-loaded nanostructured lipid carrier
更新于2025-09-23 15:21:01
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A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity
摘要： Despite the progress in nanotechnology for biomedical applications, great efforts are still being employed in optimizing nanoparticle (NP) design parameters to improve functionality and minimize bionanotoxicity. In this study, we developed CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) that are compact ligand-coated and surface-functionalized with an HIV-1-derived TAT cell-penetrating peptide (CPP) analog to improve both biocompatibility and cellular uptake. Multiparametric studies were performed in different mammalian and murine cell lines to compare the effects of varying QD size and number of surface CPPs on cellular uptake, viability, generation of reactive oxygen species, mitochondrial health, cell area, and autophagy. Our results showed that the number of cell-associated NPs and their respective toxicity are higher for the larger QDs. Meanwhile, increasing the number of surface CPPs also enhanced cellular uptake and induced cytotoxicity through the generation of mitoROS and autophagy. Thus, here we report the optimal size and surface CPP combinations for improved QD cellular uptake.
关键词： cellular uptake,mitochondrial health,cytotoxicity,biomedical applications,reactive oxygen species,nanotechnology,autophagy,quantum dots
更新于2025-09-19 17:13:59
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Aggregate Formation of BODIPY-Tethered Oligonucleotides That Led to Efficient Intracellular Penetration and Gene Regulation
摘要： Exogenous nucleic acids showed low e?ciency regarding cellular uptake and low stability in biological conditions; therefore, a number of techniques have been developed to improve their basic properties. One of the best solutions is the application of nanosized particles consisting of oligonucleotides that penetrate the cell membrane without any additives and exhibit high stability in cells. In this report, we employed a simple approach to address the basic properties of nanoparticles of oligonucleotides in biological systems. We prepared BODIPY-labeled oligonucleotides that carried an exclusive modi?cation at the strand end. BODIPY shows high hydrophobicity and ?uorescent emission; therefore, the oligonucleotides formed nanosized aggregates in aqueous solution and their behaviors in cells or tissues were easily revealed that aggregate formation was tracked. Detailed experiments indispensable for the oligonucleotides via scavenger-receptor-mediated endocytosis. In addition, the aggregates provided an e?cient gene regulation in living cells and tumor tissues transplanted into mice.
关键词： gene regulation,aggregate formation,BODIPY,cellular uptake,amphiphilic oligonucleotides
更新于2025-09-16 10:30:52
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Quantum dot cellular uptake and toxicity in the developing brain: implications for use as imaging probes
摘要： Nanometer-sized luminescent semiconductor quantum dots (QDs) have been utilized as imaging and therapeutic agents in a variety of disease settings, including diseases of the central nervous system. QDs have several advantages over traditional fluorescent probes including their small size (5–10 nm), tunable excitation and emission spectra, tailorable surface functionality, efficient photoluminescence, and robust photostability, which are ideal characteristics for in vivo imaging. Although QDs are promising imaging agents in brain-related applications, no systematic evaluation of QD behavior in brain-relevant conditions has yet been done. Therefore, we sought to investigate QD colloidal stability, cellular uptake, and toxicity in vitro, ex vivo, and in vivo in the brain environment. We found that QD behavior is highly dependent on surface functionality and that treatment of cultured organotypic whole hemisphere (OWH) slices with QDs results in dose-dependent toxicity and metallothionein increase, but no subsequent mRNA expression level changes in inflammatory cytokines or other oxidative stress. QDs coated with poly(ethylene glycol) (PEG) were protected from aggregation in neurophysiologically relevant fluids and allowed for greater penetration in tissue. Importantly, QD behavior differed in cultured slices as compared to monolayer cell cultures, and behavior in cultured slices aligned more closely with that seen in vivo. Irrespective of surface chemistry and brain-relevant platform, non-aggregated QDs were primarily internalized by microglia in a region-dependent manner both in slices and in vivo upon systemic administration. This knowledge will help guide further engineering of candidate QD-based imaging probes for neurological application.
关键词： brain,imaging probes,quantum dots,colloidal stability,cellular uptake,toxicity
更新于2025-09-11 14:15:04
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Investigation of photo-induced electron transfer between amino-functionalized graphene quantum dots and selenium nanoparticle and it's application for sensitive fluorescent detection of copper ions
摘要： Copper ions play an essential role in some biological processes. Currently, there is a need for the development of convenient and reliable analytical methods for the Cu2+ measurement. In the present work, a sensitive fluorescence method was developed for the determination of copper ions. Amino-functionalized graphene quantum dots (af-GQDs) and selenium nanoparticles (Se NPs) were synthetized, respectively, and they were characterized via transmission electron microscope, infrared spectrum analysis and X-ray photoelectron spectrum measurement. Photo-induced electron transfer (PET) between the prepared two nanomaterials could effectively quench the fluorescence of af-GQDs. Cu(II) was reduced to Cu(I) in the presence ascorbic acid and Cu2Se was finally generated on Se NPs surface, which led to the declined PET efficiency and inhibited the fluorescence quenching of af-GQDs. The change in fluorescence intensity was linearly correlated to the logarithm of the Cu2+ concentration from 1 nM to 10 μM, with a detection limit of 0.4 nM under the optimal conditions. The detections of copper ions in water samples were realized via standard addition method and the recovery values varied from 98.7% to 103%. The proposed fluorescence method was also employed to analyze the uptake of Cu2+ into human cervical carcinoma HeLa cells and cisplatin-resistant HeLa cells (HeLa/DDP cells). The experimental results indicate that the decreased hCTR1 expression level in HeLa/DDP cells weakened the uptake of copper ions into these drug-resistant tumor cells.
关键词： photo-induced electron transfer,selenium nanoparticles,cellular uptake,copper ions,fluorescence quenching,amino-functionalized graphene quantum dots
更新于2025-09-11 14:15:04