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1.
J Phys Chem B ; 125(42): 11650-11659, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34657432

RESUMO

Nanoparticles have become popular photosensitizers for photothermal therapy (PTT), as they can be targeted to specific cancer tissues and deliver a chemotherapeutic drug, providing a multimodal therapeutic approach. Photothermal conversion efficiency of nanoparticles is critical in the assessment of their therapeutic use in PTT. We describe an accurate calorimetric method for the determination of the photothermal conversion efficiency of nanoparticles in solution. A tightly focused laser beam was used to irradiate a cuvette containing a solution of silver sulfide-glutathione quantum dots (Ag2S-GSH QDs), and the maximum steady-state temperature rise was measured with an infrared camera. The data were analyzed using two different photothermal conversion efficiencies, the intrinsic and external conversion efficiencies, to relate the induced heating power of the nanoparticles to the absorbed and incident optical powers, respectively. Measurements with a tunable Ti3+:sapphire laser showed that the intrinsic photothermal conversion efficiency of Ag2S-GSH QDs exceeded 91% over the 720-810 nm wavelength range. The method was also used to analyze poly(acrylic acid)-coated superparamagnetic iron oxide nanoparticles (PAA/SPIONs), and the intrinsic photothermal conversion efficiency was determined to be 83.4% at 810 nm. This approach is useful for the evaluation of various potential nanoparticles for photothermal therapy applications.


Assuntos
Nanopartículas , Pontos Quânticos , Glutationa , Fármacos Fotossensibilizantes , Fototerapia , Terapia Fototérmica
2.
Nanoscale ; 13(35): 14879-14899, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533177

RESUMO

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.


Assuntos
Neoplasias Colorretais , Fotoquimioterapia , Pontos Quânticos , Ácido Aminolevulínico/farmacologia , Linhagem Celular Tumoral , Cetuximab/farmacologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Humanos , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas
3.
J Photochem Photobiol B ; 213: 112082, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33221627

RESUMO

Multifunctional quantum dots (QDs) with photothermal therapy (PTT) potential loaded with an anticancer drug and labelled with a targeting agent can be highly effective nano-agents for tumour specific, image-guided PTT/chemo combination therapy of cancer. Ag-chalcogenides are promising QDs with good biocompatibility. Ag2S QDs are popular theranostic agents for imaging in near-infrared with PTT potential. However, theranostic applications of AgInS2 QDs emitting in the visible region and its PTT potential need to be explored. Here, we first present a simple synthesis of small, glutathione (GSH) coated AgInS2 QDs with peak emission at 634 nm, 21% quantum yield, and excellent long-term stability without an inorganic shell. Ag2S-GSH QDs emitting in the near-infrared region (peak emission = 822 nm) were also produced. Both QDs were tagged with folic acid (FA) and conjugated with methotrexate (MTX). About 3-fold higher internalization of FA-tagged QDs by folate-receptor (FR) overexpressing HeLa cells than HT29 and A549 cells was observed. Delivery of MTX by QD-FA-MTX reduced the IC50 of the drug from 10 µg/mL to 2.5-5 µg/mL. MTX release was triggered at acidic pH, which was further enhanced with local temperature increase created by laser irradiation. Irradiation of AgInS2-GSH QDs at 640 nm (300 mW) for 10 min, caused about 10 °C temperature increase but did not cause any thermal ablation of cells. On the other hand, Ag2S-GSH-FA based PTT effectively and selectively killed HeLa cells with 10 min 808 nm laser irradiation via mostly necrosis with an IC50 of 5 µg Ag/mL. Under the same conditions, IC50 of MTX was reduced to 0.21 µg/mL if Ag2S-GSH-FA.


Assuntos
Antineoplásicos/química , Receptor 1 de Folato/metabolismo , Ácido Fólico/metabolismo , Metotrexato/química , Pontos Quânticos/química , Prata/química , Células A549 , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Terapia Combinada , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Receptor 1 de Folato/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Células HT29 , Células HeLa , Humanos , Hipertermia Induzida , Metotrexato/farmacologia , Terapia Fototérmica , Exposição à Radiação , Nanomedicina Teranóstica
4.
Mol Biol Rep ; 47(6): 4117-4129, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32436042

RESUMO

Near-infrared quantum dots (NIR QDs) are promising candidate for the fluorescent probes due to their better penetration depth, long-lived luminescence with size-tunable photoluminescence wavelengths. Glutathione-coated silver sulfide quantum dots (GSH-Ag2S QDs) were synthesized using AgNO3 and Na2S in the aqueous media and they can give reaction with glutathione reductase (GR) and glutathione-s transferase (GST) enzymes as acting substrate analogue in vitro. Investigation of the toxicity of the nanomaterials are necessary to use them in the medical field and biomedical applications. Thus, in this study we investigated biocompatibility of the GSH-Ag2S QDs in vitro using 293 T and CFPAC-1 cell lines. Cell viability by MTT assay, light microscopy, fluorescence microscopy, oxidative stress enzyme activities and ICP-MS analysis were performed to evaluate the cytotoxicity and internalization of the GSH-Ag2S QDs. GSH-Ag2S QDs showed great biocompatibility with both cell lines and did not cause imbalance in the oxidative stress metabolism. The ultralow solubility product constant of Ag2S QDs (Ksp = 6.3 × 10-50) prevents release of Ag ions into the biological systems that is in agreement with data obtained by ICP-MS. In conclusion, this data prove potential of GSH-Ag2S QDs as a biocompatible optical probe to be used for the detection and/or targeting of GSH impaired diseases including cancer.


Assuntos
Glutationa/metabolismo , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/análise , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Glutationa Redutase/metabolismo , Células HEK293/efeitos dos fármacos , Humanos , Teste de Materiais/métodos , Estresse Oxidativo , Pontos Quânticos/análise , Prata/química , Prata/metabolismo , Compostos de Prata/química
5.
Chem Biol Drug Des ; 94(6): 2094-2102, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31452310

RESUMO

Quantum dots (QD) are being evaluated as inorganic nanoparticles for both in vitro and in vivo optical imaging. They are also used as sensors or vehicles for targeted drug delivery combined with optical imaging. In this study, we demonstrated that glutathione-coated Ag2 S QDs (GSH-Ag2 S QDs) act as a substrate analogue of glutathione S-transferase (GST) enzymes for the first time in the literature. The GSTs belong to a major group of detoxification enzymes involved in the detoxification metabolism responsible for the protection of cells against reactive oxygen species (ROS) or electrophiles. GST isozymes are impaired in the various diseases such as neurological diseases and cancer. We evaluated the interaction of GST-pi enzyme with GSH-Ag2 S QDs, which have never been studied in the literature before, using both fluorometric and spectrophotometric methods. Our data showed that GSH-Ag2 S QDs gave reaction with GST enzyme as a substrate analogue. In conclusion, our data may help to guide researchers for further development of sensing systems for GST activity which is impaired in various diseases including cancer.


Assuntos
Glutationa S-Transferase pi/metabolismo , Glutationa/química , Pontos Quânticos/química , Compostos de Prata/química , Animais , Linhagem Celular Tumoral , Glutationa S-Transferase pi/química , Humanos , Isoenzimas/química , Isoenzimas/metabolismo , Cinética , Fígado/enzimologia , Fígado/metabolismo , Pontos Quânticos/metabolismo , Ratos , Ratos Wistar , Especificidade por Substrato
6.
Talanta ; 194: 501-506, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609564

RESUMO

Glutathione (GSH), a key player in various cellular processes including detoxification, anti-oxidant defense system and cell proliferation is also a potentially good coating material for luminescent quantum dots. GSH is oxidized to oxidized glutathione (GSSG) under oxidative stress and then reduced back by glutathione reductase (GR) enzyme to maintain the balance of GSH/GSSG ratio. In this frame, GSH stabilized quantum dots (QDs) have never been evaluated as GR substrate. Here, GSH coated Ag2S QDs, luminescent in the medical window, were prepared and their GR activity were tested. We have shown by spectrophotometric methods that GSH-Ag2S acted as a substrate-analog for GR enzyme that had lower activity compared to the original substrate GSSG. These results provide a new perspective in the evaluation of QDs in medical applications, enzyme activity or level detection as well as possible means to study enzymes.


Assuntos
Glutationa Redutase/metabolismo , Glutationa/química , Glutationa/metabolismo , Pontos Quânticos/química , Compostos de Prata/química , Cinética
7.
Expert Opin Drug Deliv ; 12(7): 1071-87, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25601356

RESUMO

INTRODUCTION: It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as "rolled graphite sheets inserted into each other". Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. AREAS COVERED: This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. EXPERT OPINION: In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts.


Assuntos
Sistemas de Liberação de Medicamentos , Nanotubos de Carbono , Preparações Farmacêuticas/administração & dosagem , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas
8.
Expert Opin Drug Deliv ; 12(7): 1089-105, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25613837

RESUMO

INTRODUCTION: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. AREAS COVERED: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. EXPERT OPINION: CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects.


Assuntos
Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanotubos de Carbono , Animais , Antineoplásicos/administração & dosagem , Terapia Genética/métodos , Vetores Genéticos , Humanos , Plasmídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem
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