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1.
Nanoscale ; 15(42): 17085-17096, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37847496

ABSTRACT

Biomedical photothermal therapy with optical nanoparticles is based on the conversion of optical energy into heat through three steps: optical absorption, thermal conversion of the absorbed energy and heat transfer to the surrounding medium. The light-to-heat conversion efficiency (LHCE) has become one of the main metrics to quantitatively characterize the last two steps and evaluate the merit of nanoparticules for photothermal therapy. The estimation of the LHCE is mostly performed by monitoring the temperature evolution of a solution under laser irradiation. However, this estimation strongly depends on the experimental set-up and the heat balance model used. We demonstrate here, theoretically and experimentally, that the LHCE at multiple wavelengths can be efficiently and directly determined, without the use of models, by calibrated photoacoustic spectroscopy. The method was validated using already characterized colloidal suspensions of silver sulfide nanoparticles and maghemite nanoflowers and an uncertainty of 3 to 7% was estimated for the LHCE determination. Photoacoustic spectroscopy provides a new, precise and robust method of analysis of the photothermal capabilities of aqueous solutions of nanoagents.

2.
ACS Biomater Sci Eng ; 9(7): 4126-4137, 2023 07 10.
Article in English | MEDLINE | ID: mdl-37294926

ABSTRACT

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 µg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.


Subject(s)
Breast Neoplasms , Nanoparticles , Photochemotherapy , Humans , Female , Aminolevulinic Acid , Breast Neoplasms/drug therapy , Reactive Oxygen Species , Manganese Compounds/pharmacology , Hydrogen Peroxide , Oxides/pharmacology , Phototherapy , Nanoparticles/therapeutic use
3.
Inorg Chem ; 61(6): 2846-2863, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35104130

ABSTRACT

Silver-indium-sulfide quantum dots (AIS QDs) have potential applications in many areas, including biomedicine. Their lack of regulated heavy metals, unlike many commercialized QDs, stands out as an advantage, but the necessity for alloyed or core-shell structures and related costly and sophisticated processes for the production of stable and high quantum yield aqueous AIS QDs are the current challenges. The present study demonstrates the one-step aqueous synthesis of simple AgInS2 QD compositions utilizing for the first time either a polyethyleneimine/2-mercaptopropionic acid (AIS-PEI/2MPA) mixture or only 2-mercaptopropionic acid (AIS-2MPA) as the stabilizing molecules, providing a AgInS2 portfolio consisting of cationic and anionic AIS QDs, respectively, and tuneable emission. Small AIS QDs with long-term stability and high quantum yields (19-23%) were achieved at a molar ratio of Ag/In/S 1/10/10 in water without any dopant or a semiconductor shell. The theranostic potential of these cationic and anionic AIS QDs was also evaluated in vitro. Non-toxic doses were determined, and fluorescence imaging potential was demonstrated. More importantly, these QDs were electrostatically loaded with zwitterionic 5-aminolevulinic acid (ALA) as a prodrug to enhance the tumor availability of ALA and to improve ALA-induced porphyrin photodynamic therapy (PDT). This is the first study investigating the influence of nanoparticle charge on ALA binding, release, and therapeutic efficacy. Surface charge was found to be more critical in cellular internalization and dark toxicity rather than drug loading and release. Both QDs provided enhanced ALA release at acidic pH but protected the prodrug at physiological pH, which is critical for tumor delivery of ALA, which suffers from low bioavailability. The PDT efficacy of the ALA-loaded AIS QDs was tested in 2D monolayers and 3D constructs of HT29 and SW480 human colon adenocarcinoma cancer cell lines. The incorporation of ALA delivery by the AIS QDs, which on their own do not cause phototoxicity, elicited significant cell death due to enhanced light-induced ROS generation and apoptotic/necrotic cell death, reducing the IC50 for ALA dramatically to about 0.1 and 0.01 mM in anionic and cationic AIS QDs, respectively. Combined with simple synthetic methods, the strong intracellular photoluminescence of AIS QDs, good biocompatibility of especially the anionic AIS QDs, and the ability to act as drug carriers for effective PDT signify that the AIS QDs, in particular AIS-2MPA, are highly promising theranostic QDs.


Subject(s)
Aminolevulinic Acid/pharmacology , Antineoplastic Agents/pharmacology , Photochemotherapy , Photosensitizing Agents/pharmacology , Quantum Dots/chemistry , Aminolevulinic Acid/chemical synthesis , Aminolevulinic Acid/chemistry , Anions/chemical synthesis , Anions/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cations/chemical synthesis , Cations/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Indium/chemistry , Optical Imaging , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Silver/chemistry , Sulfides/chemistry , Tumor Cells, Cultured , Water/chemistry
4.
J Phys Chem B ; 125(42): 11650-11659, 2021 10 28.
Article in English | MEDLINE | ID: mdl-34657432

ABSTRACT

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.


Subject(s)
Nanoparticles , Quantum Dots , Glutathione , Photosensitizing Agents , Phototherapy , Photothermal Therapy
5.
Nanoscale ; 13(35): 14879-14899, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34533177

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms , Photochemotherapy , Quantum Dots , Aminolevulinic Acid/pharmacology , Cell Line, Tumor , Cetuximab/pharmacology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/drug therapy , Humans , Optical Imaging , Photosensitizing Agents/pharmacology , Protoporphyrins
6.
J Photochem Photobiol B ; 213: 112082, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33221627

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/chemistry , Folate Receptor 1/metabolism , Folic Acid/metabolism , Methotrexate/chemistry , Quantum Dots/chemistry , Silver/chemistry , A549 Cells , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Combined Modality Therapy , Dose-Response Relationship, Drug , Drug Liberation , Folate Receptor 1/genetics , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , HT29 Cells , HeLa Cells , Humans , Hyperthermia, Induced , Methotrexate/pharmacology , Photothermal Therapy , Radiation Exposure , Theranostic Nanomedicine
7.
Mol Biol Rep ; 47(6): 4117-4129, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32436042

ABSTRACT

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.


Subject(s)
Glutathione/metabolism , Quantum Dots/chemistry , Quantum Dots/metabolism , Cell Survival , Coated Materials, Biocompatible/analysis , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Glutathione Reductase/metabolism , HEK293 Cells/drug effects , Humans , Materials Testing/methods , Oxidative Stress , Quantum Dots/analysis , Silver/chemistry , Silver/metabolism , Silver Compounds/chemistry
8.
Chem Biol Drug Des ; 94(6): 2094-2102, 2019 12.
Article in English | MEDLINE | ID: mdl-31452310

ABSTRACT

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.


Subject(s)
Glutathione S-Transferase pi/metabolism , Glutathione/chemistry , Quantum Dots/chemistry , Silver Compounds/chemistry , Animals , Cell Line, Tumor , Glutathione S-Transferase pi/chemistry , Humans , Isoenzymes/chemistry , Isoenzymes/metabolism , Kinetics , Liver/enzymology , Liver/metabolism , Quantum Dots/metabolism , Rats , Rats, Wistar , Substrate Specificity
9.
Talanta ; 194: 501-506, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30609564

ABSTRACT

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.


Subject(s)
Glutathione Reductase/metabolism , Glutathione/chemistry , Glutathione/metabolism , Quantum Dots/chemistry , Silver Compounds/chemistry , Kinetics
10.
Expert Opin Drug Deliv ; 12(7): 1071-87, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25601356

ABSTRACT

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.


Subject(s)
Drug Delivery Systems , Nanotubes, Carbon , Pharmaceutical Preparations/administration & dosage , Gene Transfer Techniques , Genetic Therapy/methods , Humans , Hydrophobic and Hydrophilic Interactions
11.
Expert Opin Drug Deliv ; 12(7): 1089-105, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25613837

ABSTRACT

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.


Subject(s)
Drug Delivery Systems , Gene Transfer Techniques , Nanotubes, Carbon , Animals , Antineoplastic Agents/administration & dosage , Genetic Therapy/methods , Genetic Vectors , Humans , Plasmids/administration & dosage , RNA, Small Interfering/administration & dosage
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