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Perfluorocarbon-Loaded and Redox-Activatable Photosensitizing Agent with Oxygen Supply for Enhancement of Fluorescence/Photoacoustic Imaging Guided Tumor Photodynamic Therapy
摘要： The wide clinical application of photodynamic therapy (PDT) is hampered by poor water solubility, low tumor selectivity, and nonspecific activation of photosensitizers, as well as tumor hypoxia which is common for most solid tumors. To overcome these limitations, tumor-targeting, redox-activatable, and oxygen self-enriched theranostic nanoparticles are developed by synthesizing chlorin e6 (Ce6) conjugated hyaluronic acid (HA) with reducible disulfide bonds (HSC) and encapsulating perfluorohexane (PFH) within the nanoparticles (PFH@HSC). The fluorescence and phototoxicity of PFH@HSC nanoparticles are greatly inhibited by a self-quenching effect in an aqueous environment. However, after accumulating in tumors through passive and active tumor-targeting, PFH@HSC appear to be activated from “OFF” to “ON” in photoactivity by the redox-responsive destruction of the vehicle’s structure. In addition, PFH@HSC can load oxygen within lungs during blood circulation, and the oxygen dissolved in PFH is slowly released and diffuses over the entire tumor, finally resulting in remarkable tumor hypoxia relief and enhancement of PDT efficacy by generating more singlet oxygen. Taking advantage of the excellent imaging performance of Ce6, the tumor accumulation of PFH@HSC can be monitored by fluorescent and photoacoustic imaging after intravenous administration into tumor-bearing mice. This PFH@HSC nanoparticle might have good potential for dual imaging-guided PDT in hypoxic solid tumor treatment.
关键词： tumor hypoxia,hyaluronic acid nanoparticles,perfluorocarbon,redox-responsive,photodynamic therapy
更新于2025-11-19 16:46:39
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Photosensitizer–conjugated Cu-In-S heterostructured nanorods for cancer targeted photothermal/photodynamic synergistic therapy
摘要： Photo-activated therapy is a non-invasive and promising medical technology for the treatment of cancers. Herein, we present Ce6-HA-CIS phototherapeutic nanohybrids composed of Cu-In-S (CIS) heterostructured nanorod (HS-rod), chlorin e6 (Ce6), and hyaluronic acid (HA) for the use in targeted photodynamic/photothermal therapy (PDT/PTT). In the Ce6-HA-CIS nanohybrids, the CIS HS-rod was investigated as a PTT agent to convert light into thermal energy, with Ce6 acting as a PDT agent to generate singlet oxygen (1O2). HA encapsulated the surface of the CIS HS-rod and aided the hydrophobic CIS HS-rod in achieving aqueous solubility. HA also acts as a tumor-specific targeting vector of cancer cells bearing the cluster determinant 44 receptor. Under light irradiation, the fabricated Ce6-HA-CIS nanohybrids exhibited high photothermal conversion efficiency, good photo-stability, and satisfactory photodynamic activity. In vitro and in vivo experiments demonstrated that Ce6-HA-CIS showed low cytotoxicity and synergistic photodynamic and photothermal cancer cell killing effects as compared to PTT or PDT agents alone. Therefore, these phototherapeutic nanohybrids may enhance cancer therapy in future clinical applications.
关键词： Cu-In-S,Nanohybrids,Hyaluronic acid,Photodynamic therapy,Photothermal therapy
更新于2025-11-14 17:04:02
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Cancer Selective Turn-on Fluorescence Imaging Using a Biopolymeric Nanocarrier
摘要： Most nanoparticle-based bioresearch for clinical applications is unable to overcome the clinical barriers of efficacy (e.g., sensitivity and selectivity), safety for human use, and mass-production processes. Here, we proposed a promising concept of using a biocompatible nanocarrier that delivers natural fluorescent precursors into cancerous cells. The nanocarrier is a biopolymeric nanoparticle that can be easily loaded with fluorescent precursors to form a fluorescent moiety via a biosynthesis pathway. Once delivered into cancerous cells, the nanocarriers are selectively turned on and distinctively fluoresce upon excitation. We, therefore, demonstrated the efficacy of the selective turn-on fluorescence of the nanocarriers in in vitro co-culture models and in vivo tumor-bearing models.
关键词： Hyaluronic Acid,Cancer Diagnosis,Biocompatible Nanocarrier,Turn-on Fluorescence,5-Aminolevulinic Acid
更新于2025-09-23 15:22:29
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Hyaluronic Acid-zinc Protoporphyrin Conjugates for Photodynamic Antitumor Therapy
摘要： Zinc (II) protoporphyrin IX (ZnPP) strongly inhibits antioxidative enzyme heme oxygenase-1 (HO-1), and ZnPP generates reactive oxygen species (ROS) upon light irradiation. ZnPP can induce lethal oxidative stress in the tumor, when ZnPP is selectively delivered to the tumor followed by light irradiation. In this study, ZnPP was conjugated to hyaluronic acid (HA-ZnPP) for improving its solubility in aqueous media and tumor selective delivery of ZnPP by the enhanced permeability and retention (EPR) effect. Though photosensitizing activity of the HA-ZnPP was quenched in phosphate buffered saline, it was partially recovered by addition of lecithin. Similar to other polymer-conjugated ZnPP, cellular uptake of the HA-ZnPP was lower than that of the free ZnPP in HeLa cells. In tumor-bearing mice, plasma half-life of HA-ZnPP became longer than that of free ZnPP, and thus selective accumulation of the HA-ZnPP in the tumor by the EPR effect was observed. Combination of the HA-ZnPP and light irradiation potentially suppressed the tumor growth, approximately 60% tumor volume reduction was observed without apparent adverse effects at day 31 after the drug treatment. These data demonstrate that HA is a preferable carrier for ZnPP, and the HA-conjugated ZnPP is a promising antitumor agent for photodynamic therapy.
关键词： Nanomedicine,EPR,Zinc protoporphyrin,Photodynamic therapy,Hyaluronic acid
更新于2025-09-23 15:22:29
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Interactive tissue reactions of 1064a??nm focused picoseconda??domain laser and dermal cohesive polydensified matrix hyaluronic acid treatment in in vivo rat skin
摘要： Background: Picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element (DOE) generates micro-injury zones in the epidermis and upper dermis. Objective: To investigate interactive tissue reactions between MLA-type picosecond laser pulses and cohesive polydensified matrix hyaluronic acid (CPMHA) filler in the dermis. Methods: In vivo rats with or without CPMHA pretreatment were treated with a 1064-nm picosecond-domain neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using an MLA or DOE. Skin samples were obtained at post-treatment days 1, 10, and 21 and histologically and immunohistochemically analyzed. Results: Picosecond-domain Nd:YAG laser treatment with an MLA-type or a DOE-type handpiece generated fractionated zones of pseudo-cystic cavitation along the lower epidermis and/or upper papillary dermis at Day 1. At Day 21, epidermal thickness, dermal fibroblasts, and collagen fibers had increased. Compared to CPMHA-untreated rats, rats pretreated with CPMHA showed marked increases in fibroblasts and collagen fibers in the papillary dermis. Immunohistochemical staining for the hyaluronic acid receptor CD44 revealed that MLA-type picosecond laser treatment upregulated CD44 expression in the basilar epidermis and dermal fibroblasts. Conclusions: We suggest that the hyaluronic acid-rich environment associated with CPMHA treatment may enhance MLA-type picosecond-domain laser-induced tissue reactions in the epidermis and upper dermis.
关键词： laser,neodymium-doped yttrium aluminum garnet,cohesive polydensified matrix hyaluronic acid,laser-induced tissue breakdown,CD44,picosecond
更新于2025-09-23 15:19:57
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Impact of refractive index increment on the determination of molecular weight of hyaluronic acid by muti-angle laser light-scattering technique
摘要： Hyaluronic acid (HA) is applied in a number of medical applications and HA of different molecular weight (Mw) are used in different pharmaceutical preparations. In determination of Mw by muti-angle laser light-scattering (MALS), refractive index increment (dn/dc) is an important parameter for accuracy. Herein, the influence of dn/dc on the Mw of HA in stroke-physiological saline solution is investigated by MALS in this work. Additionally, the Mw variation of HA in the manufacturing process of preparations is measured. It is shown that each HA sample corresponds to a specific value of dn/dc, which is varied from 1.38 to 1.74 L/g with the Mw increasing from 13.5 to 2840 kDa in solution. It is indicated by the results from both MALS approach and viscometry that appropriate dn/dc should be selected for Mw determination. In steam sterilization process of preparations at 121 °C, the Mw and conformation of HA can be accurately and rapidly determined by MALS. This work provides a precise method to determine the Mw of HA in the medical applications and preparation industries.
关键词： Molecular weight,Viscometry,Muti-angle laser light-scattering,Steam sterilization,Hyaluronic acid,Refractive index increment
更新于2025-09-23 15:19:57
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β-Cyclodextrin–Hyaluronic Acid Polymer Functionalized Magnetic Graphene Oxide Nanocomposites for Targeted Photo-Chemotherapy of Tumor Cells
摘要： A multifunctional targeted drug delivery platform (CDHA–MGO) has been successfully constructed by grafting β-cyclodextrin–hyaluronic acid polymers (CDHA) to Fe3O4–graphene oxide (MGO). The obtained CDHA–MGO nanocomposite has good water-dispersibility, easy magnetic separation, high near-infrared (NIR) photothermal heating, and excellent biocompatibility. The β-cyclodextrin-hyaluronic acid polymers ef?caciously enhance the doxorubicin (DOX) loading amount up to 485.43 mg·g?1. Meanwhile, the Fe3O4–graphene oxide provides a facile photothermal response mechanism to handle the NIR-triggered release of DOX in weak acidic solvent environments. Signi?cantly, the DOX-loaded nanocomposite (DOX@CDHA–MGO) has displayed CD44 receptor-mediated active targeting recognition and chemo-photothermal synergistic therapy of hepatoma cells. These ?ndings suggest that the as-prepared drug delivery platform would be of valuable potential for cancer-targeted photo-chemotherapy.
关键词： β-cyclodextrin,magnetic graphene oxide,photo-chemotherapy,near-infrared,hyaluronic acid
更新于2025-09-19 17:15:36
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Evaluation of the Bactericidal Activity of a Hyaluronic Acid-Vehicled Clarithromycin Antibiotic Mixture by Confocal Laser Scanning Microscopy
摘要： Confocal laser scanning microscopy (CLSM) was used to evaluate the antibacterial effect and depth of action of a novel clarithromycin-containing triple antibiotic mixture, which was proposed for root canal disinfection in dental pulp regeneration. A previous study reported that this mixture had no tooth discoloration effects in vitro. After infection with Enterococcus faecalis for 3 weeks, the dentinal tubules in the cylindrical root specimens were exposed to different antibiotic mixtures: ciprofloxacin, metronidazole and minocycline (3-MIX); ciprofloxacin, metronidazole and clarithromycin (3-MIXC) and ciprofloxacin and metronidazole (2-MIX). Each antibiotic formulation was mixed with macrogol (MG) or hyaluronic acid (HA) vehicles. CLSM and viability staining were used to quantitatively analyze the mean depth of the antibacterial effect and the proportions of dead and live bacteria inside the dentinal tubules. The 3-MIX and 3-MIXC demonstrated a similar depth of action. The mean proportion of dead bacteria was similar in the 3-MIX and 3-MIXC groups, and both were statistically higher than that of 2-MIX (p = 0.014). Each antibiotic mixture showed a higher bactericidal efficacy if conveyed with HA, compared to MG (3-MIX, p = 0.019; 3-MIXC, p = 0.013 and 2-MIX, p = 0.0125). The depth of action and the antibacterial efficacy of 3-MIXC seemed comparable with 3-MIX.
关键词： triple antibiotic paste,confocal laser scanning microscopy,double antibiotic paste,regenerative endodontic procedures,hyaluronic acid
更新于2025-09-19 17:13:59
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Synthesis and Characterization of Photoresponsive Macromolecule for Biomedical Application
摘要： Azobenzene, a photo switcher, has attracted increasing interest due to its structural response to photo stimulus in the field of information science and chemical sensing in the recent decades. However, limited water solubility and cytotoxicity restrained their applications in the biomedical field. In research, HA-AZO has been designed as a water soluble photo switcher in biomedical application. Synthesized HA-AZO had good water-solubility and a stable π-π? transition absorbance peak trans-isomer. With exposure to UV, transformation from trans-isomer to cis-isomer of HA-AZO could be realized according to UV spectra. Reversely, trans-isomer could be gradually recovered from cis-isomer in the dark. Simultaneously, quick response and slow recovery could be detected in the process of structural change. Moreover, repeated illumination was further used to detect the antifatigue property of HA-AZO, which showed no sign of fatigue during 20 circles. The influence of pH value on UV spectrum for HA-AZO was investigated in the work. Importantly, in acid solution, HA-AZO no longer showed any photoresponsive property. Additionally, the status of HA-AZO under the effect of UV light was investigated by DLS results and TEM image. Finally, in vitro cytotoxicity evaluations were performed to show the effects of photoresponsive macromolecule on cells.
关键词： photoresponsive macromolecule,photo switcher,biomedical application,hyaluronic acid,azobenzene
更新于2025-09-10 09:29:36
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[IEEE 2018 EMF-Med 1st World Conference on Biomedical Applications of Electromagnetic Fields (EMF-Med) - Split, Croatia (2018.9.10-2018.9.13)] 2018 EMF-Med 1st World Conference on Biomedical Applications of Electromagnetic Fields (EMF-Med) - Electrical stimulation increases schwann cells proliferation inside hyaluronic acid conduits
摘要： After nerve injury in the peripheral nervous system (PNS), application of an appropriate electrical stimulation (ES) may increase the rate and success of nerve repair. Tubular structures to mimic nervous tracts have been conducted with promising results. Schwann cells (SCs) are the main supportive cells of neurons in the PNS. In this work, we used hyaluronic acid (HA) tubular scaffolds with SCs and applied two different current intensities (450 μA and 900 μA) in order to study their effects on cells behaviour. Our data showed a beneficial effect of ES on cell number when applying a current of 450 μA. The application of tissue engineering and ES may accelerate and increase functional recovery in the PNS.
关键词： hyaluronic acid,poly-lactic fibers,electrical stimulation,nerve guidance conduit,neural differentiation
更新于2025-09-10 09:29:36