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1.
Sci Rep ; 11(1): 17801, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34493749

ABSTRACT

Urinary tract infections (UTI) are the most common infectious diseases in the world. It is becoming increasingly tough to treat because of emergence of antibiotic resistance. So, there is an exigency to develop novel anti-virulence therapeutics to combat multi-drug resistance pathogenic strains. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) discovery has revolutionized the gene editing technology for targeted approach. The greatest obstacle for CRISPR/Cas9 is cargo delivery systems and both viral and plasmid methods have disadvantages. Here, we report a highly efficient novel CRISPR based gene editing strategy, CRISPR-dots for targeting virulence factor Fimbrial Adhesion (papG gene), the bacterial adhesion molecule. Carbon quantum dots (CQD) were used as a delivery vehicle for Cas9 and gRNA into CFT073, a UPEC strain. CQDs were covalently conjugated to cas9 and papG-targeted guide RNA (gRNA) forming a nanocomplex CRISPR-dots (Cri-dots) as confirmed by DLS and transmission electron microscopy. Cri-dots-papG significantly targeted papG as demonstrated by decrease in the expression of papG.Further papG deficient UPEC had significantly reduced adherence ability and biofilm forming ability as demonstrated by fluorescence microscopy and scanning electron microscopy. Also, papG deficient UPEC had reduced virulence as shown by significantly increased survival of Caenorhabditis elegans (C. elegans) worms compared to UPEC. Our findings suggest that targeting of papG gene using Cri-dots nanocomplexes significantly reduced the pathogenicity of UPEC. Thus, Cri-dots nanocomplex offer a novel anti-bacterial strategy against multi-drug resistant UPEC.


Subject(s)
Adhesins, Escherichia coli/genetics , CRISPR-Cas Systems , Escherichia coli Infections/microbiology , Fimbriae Proteins/genetics , Gene Editing/methods , Quantum Dots/administration & dosage , Urinary Tract Infections/microbiology , Uropathogenic Escherichia coli/genetics , Animals , Bacterial Adhesion/drug effects , Biofilms/drug effects , CRISPR-Associated Protein 9/administration & dosage , CRISPR-Associated Protein 9/genetics , Caenorhabditis elegans/microbiology , Carbon , Drug Delivery Systems , Escherichia coli K12/drug effects , Escherichia coli K12/genetics , HeLa Cells , Hemagglutination/drug effects , Humans , Mannose/pharmacology , Pharmaceutical Vehicles , Quantum Dots/toxicity , RNA, Guide, Kinetoplastida/administration & dosage , RNA, Guide, Kinetoplastida/genetics , THP-1 Cells , Uropathogenic Escherichia coli/drug effects , Uropathogenic Escherichia coli/isolation & purification , Uropathogenic Escherichia coli/pathogenicity , Virulence/genetics
2.
J Pharm Pharmacol ; 73(12): 1599-1608, 2021 Dec 07.
Article in English | MEDLINE | ID: mdl-34524456

ABSTRACT

OBJECTIVES: To investigate the pharmacokinetics, biodistribution and peritoneal retention of Ag2S quantum dots (Qds) after intraperitoneal (IP) injection into mice and to compare the results with those reported for the intravenous (IV) injection of these particles. METHODS: Ag2S Qds was prepared by a simple one-step co-precipitation method and was injected intraperitoneally into mice. Six animals were sacrificed at predetermined time points, and blood, peritoneal content and tissue samples were collected. Ag concentration that represents the concentration of Qds was analysed by atomic absorption spectrophotometry. KEY FINDINGS: Detectability of Qds in the peritoneal sample up to 2 h indicated that, compared with small drug molecules, the absorption of Ag2S Qds from the peritoneal cavity occurred at a slower rate. The AUC tissue/AUC blood ratio in the liver and intestine after IP injection (0.55 and 0.98, respectively) was considerably lower than those for the bolus injection (217 and 94, respectively), while this ratio in the spleen and lungs was markedly higher than the IV route. CONCLUSIONS: Overall, the obtained results suggest that IP injection of Ag2S Qds could be more effective for drug delivery to/imaging of the spleen and lungs, whereas the IV injection for the drug delivery to/imaging of the liver and intestine.


Subject(s)
Peritoneal Absorption , Peritoneum/metabolism , Pharmacokinetics , Quantum Dots/metabolism , Silver , Tissue Distribution , Animals , Diagnostic Imaging , Drug Carriers , Injections, Intraperitoneal , Male , Mice, Inbred Strains , Quantum Dots/administration & dosage , Silver/administration & dosage
3.
Top Curr Chem (Cham) ; 379(1): 1, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33398442

ABSTRACT

Quantum dots (QDs) have attracted considerable attention as fluorescent probes for life sciences. The advantages of using QDs in fluorescence-based studies include high brilliance, a narrow emission band allowing multicolor labeling, a chemically active surface for conjugation, and especially, high photostability. Despite these advantageous features, the size of the QDs prevents their free transport across the plasma membrane, limiting their use for specific labeling of intracellular structures. Over the years, various methods have been evaluated to overcome this issue to explore the full potential of the QDs. Thus, in this review, we focused our attention on physical and biochemical QD delivery methods-electroporation, microinjection, cell-penetrating peptides, molecular coatings, and liposomes-discussing the benefits and drawbacks of each strategy, as well as presenting recent studies in the field. We hope that this review can be a useful reference source for researches that already work or intend to work in this area. Strategies for the intracellular delivery of quantum dots discussed in this review (electroporation, microinjection, cell-penetrating peptides, molecular coatings, and liposomes).


Subject(s)
Fluorescent Dyes/administration & dosage , Quantum Dots/administration & dosage , Animals , Cell-Penetrating Peptides/chemistry , Drug Carriers/chemistry , Drug Delivery Systems/methods , Electroporation/methods , Fluorescent Dyes/analysis , Humans , Liposomes/chemistry , Microinjections/methods , Quantum Dots/analysis
4.
J Biomed Mater Res A ; 109(5): 637-648, 2021 05.
Article in English | MEDLINE | ID: mdl-32615012

ABSTRACT

A prosthetic scaffold development using fluorescent nanofiber is reported for an enhanced reepithelialization in wistar albino rats. In this study, a novel approach was followed to construct the biocompatible fluorescent nanofiber that will be helpful to monitor the tissue regeneration process. Here, a multifunctional carbon quantum dots (CQDs)-embedded electrospun polyacrylonitrile (PAN) nanofiber was fabricated and characterized using standard laboratory techniques. The biodegradation ability was assessed by simulated body fluid thereby analyzing porosity and water absorption capacity of the material. The fluorescent scaffold was tested for cytotoxicity and antimicrobial activity using bacterial and fibroblast cells and fluorescent stability was analyzed by bioimaging of animal and bacterial cells. Tissue regeneration capability of the developed scaffold was evaluated using wistar albino rats. Unlike biomicking scaffolds, the CQDs-embedded PAN-based substrate has given dual support by enhancing reepithelialization without growth factors and acted as an antimicrobial agent to provide contamination free tissue regeneration. Scaffolds were examined by using histostaining techniques and scanning electron microscopy to observe the reepithelialization in the regenerated tissues. The novel approach for developing infection free soft tissue regeneration was found to be phenomenal in scaffold development.


Subject(s)
Biocompatible Materials , Carbon , Guided Tissue Regeneration , Quantum Dots/therapeutic use , Re-Epithelialization/drug effects , Tissue Scaffolds , Acrylic Resins , Animals , Biocompatible Materials/adverse effects , Cell Adhesion , Cell Line , Epithelial Cells/cytology , Epithelial Cells/drug effects , Escherichia coli/drug effects , Escherichia coli/growth & development , Fibroblasts/drug effects , Implants, Experimental/adverse effects , Implants, Experimental/microbiology , Materials Testing , Mice , Microscopy, Electron, Scanning , Nanofibers , Quantum Dots/administration & dosage , Rats , Rats, Wistar , Skin/injuries , Surface Properties , Tissue Scaffolds/adverse effects , Wettability
5.
J Drug Target ; 29(5): 541-550, 2021 06.
Article in English | MEDLINE | ID: mdl-33307859

ABSTRACT

Quantum clusters with target specificity are suitable for tissue-specific imaging. In the present work, amorphous zinc insulin quantum clusters (IZnQCs) had been synthesised to promote and monitor wound recovery. Easy synthesis, biocompatibility, stability, enhanced quantum yield, and solubility made the cluster suitable for preclinical/clinical exploration. Zn2+ is known for its binding to insulin hexamer. Here we report the reformation of the structure in a quantum cluster form in the presence of Zn2+. The formation of IZnQCs was confirmed by the change in zeta potential from -25.6 mV to -17.9 mV and also the formation of protein metal interaction was confirmed in FTIR bands at 450, 480, and 613 cm-1 for Zn-O, Zn-N, and Zn-S, respectively. HRTEM-EDS and SAED data analysis showed an amorphous nature of the cluster. The binding of IZnQCs to the cells has been confirmed using confocal microscopy. IZnQCs showed a synergistic effect in wound recovery than insulin or Zn2+ alone. Further due to high fluorescence this recovery process can be monitored under an appropriate setup. Wound healing promotional activity, target specificity, and fluorescence properties make the IZnQCs ideal to use for bioimaging along with promoting and monitoring of wound recovery agent.


Subject(s)
Insulin/administration & dosage , Keratinocytes/drug effects , Optical Imaging/methods , Quantum Dots/administration & dosage , Skin/drug effects , Zinc/administration & dosage , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Humans , Insulin/chemical synthesis , Keratinocytes/metabolism , Quantum Dots/chemistry , Skin/cytology , Skin/metabolism , Zinc/chemistry
6.
J Mater Chem B ; 9(1): 125-130, 2021 01 07.
Article in English | MEDLINE | ID: mdl-33225328

ABSTRACT

Gram-positive bacteria are one of the most common pathogens causing severe and acute infection, and hospital infection caused by Gram-positive bacteria have increased significantly. Also, as antibiotics have been widely used, abusing of antibiotics is becoming an increasingly serious problem which is followed by dangerous drug resistance. Here, we developed a series of cationic carbon dots (CDs) with high-performance as antibacterial agents by using tartaric acid and m-aminophenol as precursors. The surface charge of these CDs can be regulated from +4.5 ± 0.42 mV to +33.2 ± 0.99 mV by increasing the contents of pyridine N and pyrrolic N in CDs. Further antibacterial experiments show that 250 µg mL-1 of CDs with +33.2 ± 0.99 mV can selectively kill Gram-positive bacteria and the antibacterial efficiency can reach approximately >99%. These CDs with positive surface charge can be selectively absorbed on the cell walls of Staphylococcus aureus (S. aureus) via electrostatic interaction and then disturb their physiological metabolism, eventually leading to bacterial death. The present work provides a novel method to adjust the surface charge of CDs and apply these CDs as alternative antibacterial agents.


Subject(s)
Aminophenols/administration & dosage , Anti-Bacterial Agents/administration & dosage , Carbon/administration & dosage , Gram-Positive Bacteria/drug effects , Quantum Dots/administration & dosage , Tartrates/administration & dosage , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Gram-Positive Bacteria/physiology , HeLa Cells , Humans , Surface Properties
7.
J Mater Chem B ; 8(46): 10650-10661, 2020 12 14.
Article in English | MEDLINE | ID: mdl-33150923

ABSTRACT

Black phosphorus quantum dots (BPQDs) with excellent biocompatibility, outstanding photothermal and photodynamic efficacies have attracted significant attention in cancer therapy. However, the low environmental stability and poor dispersity of BPQDs limit their practical applications. In the present work, biocompatible anionic waterborne polyurethane (WPU) nanoparticles were synthesized from castor oil to encapsulate the BPQDs. The WPU-BPQDs with a BPQDs loading capacity of about 13.8% (w/w) exhibited significantly improved dispersion and environmental stability without affecting the photothermal efficiency of BPQDs. Intriguingly, it was found that WPU encapsulation led to significant enhancement in the reactive oxygen species (ROS) generation of BPQDs, which indicated the enhanced photodynamic efficacy of the encapsulated BPQDs as compared to the bare BPQDs. The effect of solution pH on the ROS generation efficiency of BPQDs and the pH variation caused by BPQDs degradation was then investigated to explore the possible mechanism. In acidic solution, ROS generation was suppressed, while BPQDs degradation led to the acidification of the solution. Fortunately, after being encapsulated inside the WPU nanoparticles, the degradation rate of BPQDs became slower, while the acidic environment around BPQDs was favorably regulated by WPU nanoparticles having a special electrochemical double layer consisting of interior COO- and exterior NH(Et3)+, thus endowing the WPU-BPQDs-boosted production of ROS as compared to the bare BPQDs. Considering the undesired acidic tumor environment, this unique pH regulation effect of WPU-BPQDs would be beneficial for in vivo photodynamic efficacy. Both in vitro and in vivo experiments showed that WPU-BPQDs could effectively improve photodynamic therapy (PDT) and maintain outstanding photothermal therapy (PTT) effects. Together with the excellent dispersity, biocompatibility, and easy biodegradability, WPU-BPQDs can be a promising agent for PDT/PTT cancer treatments.


Subject(s)
Nanoparticles/chemistry , Phosphorus/chemistry , Photochemotherapy/methods , Photothermal Therapy/methods , Quantum Dots/chemistry , Reactive Oxygen Species/metabolism , Animals , Anions , Dose-Response Relationship, Drug , Female , HeLa Cells , Hep G2 Cells , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/administration & dosage , Neoplasms/drug therapy , Neoplasms/metabolism , Phosphorus/administration & dosage , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemical synthesis , Polyurethanes/administration & dosage , Polyurethanes/chemical synthesis , Quantum Dots/administration & dosage , Random Allocation , Water
8.
Theranostics ; 10(26): 12241-12262, 2020.
Article in English | MEDLINE | ID: mdl-33204340

ABSTRACT

The development of nanomedicine is expected to provide an innovative direction for addressing challenges associated with multidrug-resistant (MDR) bacteria. In the past decades, although nanotechnology-based phototherapy has been developed for antimicrobial treatment since it rarely causes bacterial resistance, the clinical application of single-mode phototherapy has been limited due to poor tissue penetration of light sources. Therefore, combinatorial strategies are being developed. In this review, we first summarized the current phototherapy agents, which were classified into two functional categories: organic phototherapy agents (e.g., small molecule photosensitizers, small molecule photosensitizer-loaded nanoparticles and polymer-based photosensitizers) and inorganic phototherapy agents (e.g., carbo-based nanomaterials, metal-based nanomaterials, composite nanomaterials and quantum dots). Then the development of emerging phototherapy-based combinatorial strategies, including combination with chemotherapy, combination with chemodynamic therapy, combination with gas therapy, and multiple combination therapy, are presented and future directions are further discussed. The purpose of this review is to highlight the potential of phototherapy to deal with bacterial infections and to propose that the combination therapy strategy is an effective way to solve the challenges of single-mode phototherapy.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/drug therapy , Photosensitizing Agents/administration & dosage , Phototherapy/methods , Theranostic Nanomedicine/methods , Animals , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Combined Modality Therapy/methods , Disease Models, Animal , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/radiation effects , Humans , Light , Nanoparticles/administration & dosage , Quantum Dots/administration & dosage
9.
Int J Nanomedicine ; 15: 8537-8552, 2020.
Article in English | MEDLINE | ID: mdl-33173291

ABSTRACT

PURPOSE: Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci. MATERIALS AND METHODS: We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots (P@QD-MdC NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model. RESULTS: Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, P@QD-MdC NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to P@QD-MdC NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice. CONCLUSION: P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.


Subject(s)
Cell Adhesion Molecules/immunology , Immunoconjugates/administration & dosage , Inflammatory Bowel Diseases/diagnostic imaging , Mucoproteins/immunology , Quantum Dots/administration & dosage , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Colitis/chemically induced , Colitis/diagnostic imaging , Crohn Disease/diagnostic imaging , Disease Models, Animal , Female , Humans , Immunoconjugates/pharmacokinetics , Injections, Intravenous , Intestinal Mucosa/diagnostic imaging , Intestines/diagnostic imaging , Magnetic Resonance Imaging/methods , Mice, Inbred C57BL , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Polyesters/chemistry , Polyethylene Glycols/chemistry , Tissue Distribution
10.
Int J Mol Sci ; 21(21)2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33137996

ABSTRACT

Waste biomass such as lignin constitutes a great raw material for eco-friendly carbon quantum dots (CQDs) synthesis, which find numerous applications in various fields of industry and medicine. Carbon nanodots, due to their unique luminescent properties as well as water-solubility and biocompatibility, are superior to traditional organic dyes. Thus, obtainment of CQDs with advanced properties can contribute to modern diagnosis and cell visualization method development. In this article, a new type of coumarin-modified CQD was obtained via a hybrid, two-step pathway consisting of hydrothermal carbonization and microwave-assisted surface modification with coumarin-3-carboxylic acid and 7-(Diethylamino) coumarin-3-carboxylate. The ready products were characterized over their chemical structure and morphology. The nanomaterials were confirmed to have superior fluorescence characteristics and quantum yield up to 18.40%. They also possessed the ability of biomolecules and ion detection due to the fluorescence quenching phenomena. Their lack of cytotoxicity to L929 mouse fibroblasts was confirmed by XTT assay. Moreover, the CQDs were proven over their applicability in real-time bioimaging. Obtained results clearly demonstrated that proposed surface-modified carbon quantum dots may become a powerful tool applicable in nanomedicine and pharmacy.


Subject(s)
Carbon/chemistry , Coumarins/chemistry , Fibroblasts/cytology , Quantum Dots/administration & dosage , Animals , Cell Proliferation , Cells, Cultured , Fibroblasts/drug effects , Fluorescent Dyes , Luminescence , Mice , Quantum Dots/chemistry
11.
Int J Mol Sci ; 21(19)2020 Sep 27.
Article in English | MEDLINE | ID: mdl-32992627

ABSTRACT

InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.


Subject(s)
Indium/chemistry , Indium/toxicity , Kidney/drug effects , Phosphines/chemistry , Phosphines/toxicity , Quantum Dots/chemistry , Quantum Dots/toxicity , Animals , Apoptosis/drug effects , Apoptosis/genetics , Carbon Dioxide/chemistry , Female , Gene Expression Regulation/drug effects , Hydroxyl Radical/chemistry , Indium/administration & dosage , Indium/pharmacokinetics , Inflammation/chemically induced , Injections, Intravenous , Kidney/metabolism , Mice , Mice, Inbred BALB C , Oxidative Stress/drug effects , Phosphines/administration & dosage , Phosphines/pharmacokinetics , Quantum Dots/administration & dosage , Sulfides/administration & dosage , Sulfides/chemistry , Sulfides/pharmacokinetics , Sulfides/toxicity , Surface Properties , Tissue Distribution , Zinc Compounds/administration & dosage , Zinc Compounds/chemistry , Zinc Compounds/pharmacokinetics , Zinc Compounds/toxicity
12.
J Mater Chem B ; 8(37): 8623-8633, 2020 09 30.
Article in English | MEDLINE | ID: mdl-32821893

ABSTRACT

The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially where less tumor-associated antigens are released from tumor sites. Herein, a Ag2S QD/DOX/Bestatin@PC10ARGD genetically engineered polypeptide hydrogel PC10ARGD as a sustained-release material was developed for mammary carcinoma treatment. A near-infrared silver sulfide (Ag2S) QD as a photosensitizer was encapsulated into the hydrophobic cavity formed by the self-assembly of the polypeptide nanogel (PC10ARGD) for photothermal therapy. The water-soluble drug DOX and Bestatin were integrated into the PC10ARGD hydrogel. The photothermal effect could trigger the sustained release of the DOX, which could be applied to initiate in situ vaccination. Bestatin as an immune-adjuvant drug could amplify the body's immune function. The results of in vivo therapy tests exhibited that the Ag2S QD/DOX/Bestatin@PC10ARGD hydrogel with laser irradiation could activate anti-tumor immune effects that inhibit the growth of primary tumors and distal lung metastatic nodules. Meanwhile, a safer lower-temperature with multiple laser irradiation treatment strategy exhibited more effective tumor-killing performance (84.4% tumor inhibition rate) and promoted the penetration of immune cells into the tumor tissue. The CD8+ and CD4+ cytotoxic T cells ratio was increased by 5.3 and 10 times, respectively, thus exhibiting a good prognostic signal. The multifunctional polypeptide hydrogel as a green manufacturing and engineering material is promising to serve as a cancer vaccine for anticancer applications.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Drug Carriers/chemistry , Hydrogels/chemistry , Peptides/chemistry , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Doxorubicin/therapeutic use , Drug Carriers/administration & dosage , Drug Carriers/toxicity , Drug Liberation , Drug Therapy , Female , Hydrogels/administration & dosage , Hydrogels/toxicity , Infrared Rays , Injections, Subcutaneous , Leucine/administration & dosage , Leucine/analogs & derivatives , Leucine/chemistry , Leucine/therapeutic use , Mice, Inbred BALB C , Peptides/administration & dosage , Peptides/toxicity , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/radiation effects , Photosensitizing Agents/therapeutic use , Photothermal Therapy , Quantum Dots/administration & dosage , Quantum Dots/radiation effects , Quantum Dots/therapeutic use , Silver Compounds/administration & dosage , Silver Compounds/radiation effects , Silver Compounds/therapeutic use
13.
Biochem Biophys Res Commun ; 529(4): 930-935, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32819601

ABSTRACT

With significantly decreased light scattering and tissue autofluorescence, fluorescence imaging in the second near infrared (NIR-II, 1000-1700 nm) region has been heavily explored in biomedical field recently. Silver sulfide quantum dots (Ag2S QDs) with unique optical properties were one of the most classic NIR-II imaging probes. However, the Ag2S QDs for in vivo purpose were mainly obtain by oil phase-based high-temperature route at present. Here, we proposed a mild aqueous route to prepare NIR-II emissive Ag2S QDs for in vivo tumor imaging. Original Ag2S QDs was obtained by mixing sodium sulfide and silver nitrate in a thiol-terminated polyethylene glycol (mPEG-SH) solution. Treating the original Ag2S QDs with extra mPEG-SH ligands produced highly PEGyalted Ag2S QDs. These re-PEGylated Ag2S QDs exhibited much better blood circulation and tumor accumulation in vivo comparing with the original ones, which can serve as excellent tumor imaging probes. The whole-body blood vessel imaging of living mice was achieved with high resolution, the bio-distribution of these QDs were studied by NIR-II imaging as well. This work also highlighted the importance of ligand density for tumor targeting.


Subject(s)
Drug Delivery Systems/methods , Hepatoblastoma/diagnostic imaging , Optical Imaging/methods , Polyethylene Glycols/chemistry , Quantum Dots/chemistry , Animals , Female , Hep G2 Cells , Heterografts , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Quantum Dots/administration & dosage , Silver Nitrate/chemistry , Sulfides/chemistry
14.
Theranostics ; 10(17): 7841-7856, 2020.
Article in English | MEDLINE | ID: mdl-32685024

ABSTRACT

Rationale: The present study reports the multifunctional anticancer activity against B16F10 melanoma cancer cells and the bioimaging ability of fluorescent nitrogen-phosphorous-doped carbon dots (NPCDs). Methods: The NPCDs were synthesized using a single-step, thermal treatment and were characterized by TEM, XPS, fluorescence and UV-Vis spectroscopy, and FTIR analysis. The anticancer efficacy of NPCDs was confirmed by using cell viability assay, morphological evaluation, fluorescent live-dead cell assay, mitochondrial potential assay, ROS production, RT-PCR, western-blot analysis, siRNA transfection, and cellular bioimaging ability. Results: The NPCDs inhibited the proliferation of B16F10 melanoma cancer cells after 24 h of treatment and induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated levels of reactive oxygen species. The NPCDs treatment further elevated the levels of pro-apoptotic factors and down-regulated the level of Bcl2 (B-cell lymphoma 2) that weakened the mitochondrial membrane, and activated proteases such as caspases. Treatment with NPCDs also resulted in dose-dependent cell cycle arrest, as indicated by reduced cyclin-dependent kinase (CDK)-2, -4, and -6 protein levels and an enhanced level of p21. More importantly, the NPCDs induced the activation of autophagy by upregulating the protein expression levels of LC3-II and ATG-5 (autophagy-related-5) and by downregulating p62 level, validated by knockdown of ATG-5. Additionally, owing to their excellent luminescence property, these NPCDs were also applicable in cellular bioimaging, as evidenced by the microscopic fluorescence imaging of B16F10 melanoma cells. Conclusion: Based on these findings, we conclude that our newly synthesized NPCDs induced cell cycle arrest, autophagy, and apoptosis in B16F10 melanoma cells and presented good cellular bioimaging capability.


Subject(s)
Antineoplastic Agents/administration & dosage , Fluorescent Dyes/chemistry , Melanoma, Experimental/drug therapy , Quantum Dots/administration & dosage , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Autophagy/drug effects , Carbon/chemistry , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Humans , Intravital Microscopy/methods , Melanoma, Experimental/pathology , Mice , Microscopy, Fluorescence/methods , Nitrogen/chemistry , Phosphorus/chemistry , Quantum Dots/chemistry , Skin Neoplasms/pathology
15.
Nat Nanotechnol ; 15(8): 698-708, 2020 08.
Article in English | MEDLINE | ID: mdl-32601447

ABSTRACT

Inherited retinal dystrophies and late-stage age-related macular degeneration, for which treatments remain limited, are among the most prevalent causes of legal blindness. Retinal prostheses have been developed to stimulate the inner retinal network; however, lack of sensitivity and resolution, and the need for wiring or external cameras, have limited their application. Here we show that conjugated polymer nanoparticles (P3HT NPs) mediate light-evoked stimulation of retinal neurons and persistently rescue visual functions when subretinally injected in a rat model of retinitis pigmentosa. P3HT NPs spread out over the entire subretinal space and promote light-dependent activation of spared inner retinal neurons, recovering subcortical, cortical and behavioural visual responses in the absence of trophic effects or retinal inflammation. By conferring sustained light sensitivity to degenerate retinas after a single injection, and with the potential for high spatial resolution, P3HT NPs provide a new avenue in retinal prosthetics with potential applications not only in retinitis pigmentosa, but also in age-related macular degeneration.


Subject(s)
Quantum Dots , Retina/drug effects , Retinitis Pigmentosa/metabolism , Animals , Disease Models, Animal , Female , Injections, Intraocular , Male , Photic Stimulation , Polymers/administration & dosage , Polymers/pharmacology , Quantum Dots/administration & dosage , Quantum Dots/therapeutic use , Rats , Rats, Sprague-Dawley , Visual Cortex/drug effects , Visual Cortex/metabolism , Visual Prosthesis
16.
Commun Biol ; 3(1): 284, 2020 06 05.
Article in English | MEDLINE | ID: mdl-32504032

ABSTRACT

Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and emissive graphene quantum dots (GQDs) were engineered named as NFGL. Further, doxorubicin hydrochloride was encapsulated in NFGL to exhibit phototriggered chemotherapy and functionalized with folic acid targeting ligands. Encapsulated agents showed imaging bimodality for in vivo tumor diagnosis due to their high contrast and emissive nature. Targeted NFGL nanohybrids demonstrated near infrared light (NIR, 750 nm) mediated tumor reduction because of generated heat and Reactive Oxygen Species (ROS). Moreover, NFGL nanohybrids exhibited remarkable ROS scavenging ability as compared to GQDs loaded liposomes validated by antitumor study. Hence, this approach and engineered system could open new direction for targeted imaging and cancer therapy.


Subject(s)
Doxorubicin/administration & dosage , Gold/administration & dosage , Graphite/administration & dosage , Liposomes/administration & dosage , Phototherapy/methods , Theranostic Nanomedicine/methods , 3T3 Cells , Animals , Antibiotics, Antineoplastic/administration & dosage , Breast Neoplasms , Cell Line, Tumor , Humans , Infrared Rays , Metal Nanoparticles/administration & dosage , Mice , Quantum Dots/administration & dosage
17.
J Ocul Pharmacol Ther ; 36(6): 467-483, 2020.
Article in English | MEDLINE | ID: mdl-32522096

ABSTRACT

Purpose: Disturbances that affect the inside of the eyeball tend to be highly harmful since they compromise the homeostasis of this organ. Alongside this, the eyeball has several anatomical barriers that prevent the entry of substances. This way, diseases that affect the retina are among those that present greater difficulty in the treatment. In many cases, abnormal proliferation of blood vessels (neovascularization) occurs from the lower layers of the retina. This process damages its structure physiologically and anatomically, causing the rapid and irreversible loss of visual capacity. This work aims to develop nanosuspensions of quantum dots (QDs) conjugated to bevacizumab. Methods: Two types of QDs were produced by aqueous route, stabilized with chitosan conjugated to bevacizumab. The antiangiogenic activity was evaluated in the chorioallantoic membrane model, in which results indicated discrete activity at the doses tested. Samples were assessed for their biosafety in animals, after intravitreal administration, by means of electroretinography (ERG), intraocular pressure (IOP) measurement, histological, morphometric, and immunohistochemical evaluation. Results: No significant alterations were detected in ERG that suggests damage to retinal function by the samples. No significant changes in IOP were also detected. The histological sections did not show signs of acute inflammation, although there was evidence of late retinal damage. The immunohistochemical analysis did not detect any apoptotic bodies. Conclusion: Preliminary results suggest that QDs present potential applicability in ocular therapy, and it is necessary to better characterize their in vivo behavior and to optimize their dosage.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Bevacizumab/pharmacology , Quantum Dots/therapeutic use , Retina/pathology , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Animals , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Chorioallantoic Membrane/drug effects , Containment of Biohazards/standards , Electroretinography/methods , Immunohistochemistry/methods , Intraocular Pressure/drug effects , Intravitreal Injections , Male , Models, Animal , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neovascularization, Pathologic/diagnosis , Neovascularization, Pathologic/drug therapy , Quantum Dots/administration & dosage , Quantum Dots/chemistry , Rats , Retinal Degeneration/diagnosis , Retinal Degeneration/metabolism , Suspensions/administration & dosage , Suspensions/chemistry , Suspensions/pharmacokinetics , Tumor Necrosis Factor Ligand Superfamily Member 15/pharmacology , Vascular Endothelial Growth Factor A/immunology
18.
Nanotheranostics ; 4(3): 173-183, 2020.
Article in English | MEDLINE | ID: mdl-32483522

ABSTRACT

Indium phosphide/zinc sulfate (InP/ZnS) quantum dots (QDs) are presumed to be less hazardous than those that contain cadmium. However, the toxicological profile has not been established. The present study investigated the acute toxicity of InP/ZnS QDs with different surface modifications (COOH, NH2, and OH) in mice after pulmonary aerosol inhalation. InP/ZnS QDs were able to pass through the blood-gas barrier and enter the circulation, and subsequently accumulated in major organs. No obvious changes were observed in the body weight or major organ coefficients. Red blood cell counts and platelet-related indicators were in the normal range, but the proportion of white blood cells was altered. The InP/ZnS QDs caused varying degrees of changes in some serum markers, but no histopathological abnormalities related to InP/ZnS QDs treatment was observed in major organs except that hyperemia in alveolar septa was found in lung sections. These results suggested that the effects of respiratory exposure to InP/ZnS QDs on the lungs need to be fully considered in future biomedical application although the overall toxicity of quantum dots is relatively low.


Subject(s)
Lung , Quantum Dots , Administration, Inhalation , Animals , Body Weight/drug effects , Female , Indium/administration & dosage , Indium/pharmacokinetics , Indium/toxicity , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Liver/drug effects , Liver/metabolism , Liver/pathology , Lung/drug effects , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Microscopy, Fluorescence , Phosphines/administration & dosage , Phosphines/pharmacokinetics , Phosphines/toxicity , Quantum Dots/administration & dosage , Quantum Dots/analysis , Quantum Dots/metabolism , Quantum Dots/toxicity , Surface Properties , Tissue Distribution , Zinc Sulfate/administration & dosage , Zinc Sulfate/pharmacokinetics , Zinc Sulfate/toxicity
20.
Biomater Sci ; 8(12): 3392-3403, 2020 Jun 21.
Article in English | MEDLINE | ID: mdl-32377654

ABSTRACT

The use of nanoscale materials (NMs) could cause problems such as cytotoxicity, genomic aberration, and effects on human health, but the impacts of NM exposure during pregnancy remain uncharacterized in the context of clinical applications. It was sought to determine whether nanomaterials pass through the maternal-fetal junction at any stage of pregnancy. Quantum dots (QDs) coated with heparinized Pluronic 127 nanogels and polyethyleneimine (PEI) were administered to pregnant mice. The biodistribution of QDs, as well as their biological impacts on maternal and fetal health, was evaluated. Encapsulation of QDs with a nanogel coating produces a petal-like nanotracer (PNt), which could serve as a nano-carrier of genes or drugs. PNts were injected through the tail vein and accumulated in the liver, kidneys, and lungs. QD accumulation in reproductive organs (uterus, placenta, and fetus) differed among phases of pregnancy. In phase I (7 days of pregnancy), the QDs did not accumulate in the placenta or fetus, but by phase III (19 days) they had accumulated at high levels in both tissues. Karyotype analysis revealed that the PNt-treated pups did not have genetic abnormalities when dams were treated at any phase of pregnancy. PNts have the potential to serve as carriers of therapeutic agents for the treatment of the mother or fetus and these results have a significant impact on the development and application of QD-based NPs in pregnancy.


Subject(s)
Drug Carriers/administration & dosage , Heparin/administration & dosage , Poloxamer/administration & dosage , Polyethyleneimine/administration & dosage , Quantum Dots/administration & dosage , Animals , Drug Carriers/pharmacokinetics , Female , Heparin/pharmacokinetics , Humans , Karyotype , Maternal-Fetal Exchange , Mesenchymal Stem Cells , Mice, Inbred ICR , Poloxamer/pharmacokinetics , Polyethyleneimine/pharmacokinetics , Pregnancy , Tissue Distribution
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