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PloS One 2019Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and...
Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox·HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox·Lipo), two common drugs for anti-cancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Feasibility Studies; Female; Humans; Injections, Intralesional; Mice; Neoplasms; Photoacoustic Techniques; Pilot Projects; Polyethylene Glycols; Theranostic Nanomedicine; Tomography
PubMed: 31150471
DOI: 10.1371/journal.pone.0217576 -
Advanced Healthcare Materials Jul 2020Cancer is the second leading cause of mortality globally. Various nanoparticles have been developed to improve the efficacy and safety of chemotherapy, photothermal...
Cancer is the second leading cause of mortality globally. Various nanoparticles have been developed to improve the efficacy and safety of chemotherapy, photothermal therapy, and their combination for treating cancer. However, most of the existing nanoparticles are low in both subcellular precision and drug loading content (<≈5%), and the effect of targeted heating of subcellular organelles on the enhancement of chemotherapy has not been well explored. Here, a hybrid Py@Si-TH nanoparticle is reported to first target cancer cells overexpressed with the variant CD44 via its natural ligand HA on the outermost surface of the nanoparticle before cellular uptake, and then target mitochondria after they are taken up inside cells. In addition, the nanoparticle is ultraefficient for encapsulating doxorubicin hydrochloride (DOX) to form Py@Si-TH-DOX nanoparticle. The encapsulation efficiency is ≈100% at the commonly used low feeding ratio of 1:20 (DOX:empty nanoparticle), and >80% at an ultrahigh feeding ratio of 1:1. In combination with near infrared (NIR, 808 nm) laser irradiation, the tumor weight in the Py@Si-TH-DOX treatment group is 8.5 times less than that in the Py@Si-H-DOX (i.e., DOX-laden nanoparticles without mitochondrial targeting) group, suggesting targeted heating of mitochondria is a valuable strategy for enhancing chemotherapy to combat cancer.
Topics: Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Heating; Mitochondria; Nanoparticles; Neoplasms
PubMed: 32548935
DOI: 10.1002/adhm.202000181 -
International Journal of Molecular... Nov 2021The article discusses the release process of doxorubicin hydrochloride (DOX) from multi-wall carbon nanotubes (MWCNTs). The studies described a probable mechanism of...
The article discusses the release process of doxorubicin hydrochloride (DOX) from multi-wall carbon nanotubes (MWCNTs). The studies described a probable mechanism of release and actions between the surface of functionalized MWCNTs and anticancer drugs. The surface of carbon nanotubes (CNTs) has been modified via treatment in nitric acid to optimize the adsorption and release process. The modification efficiency and physicochemical properties of the MWCNTs+DOX system were analyzed by using SEM, TEM, EDS, FTIR, Raman Spectroscopy and UV-Vis methods. Based on computer simulations at pH 7.4 and the experiment at pH 5.4, the kinetics and the mechanism of DOX release from MWNT were discussed. It has been experimentally observed that the acidic pH (5.4) is appropriate for the efficient release of the drug from CNTs. It was noted that under acidic pH conditions, which is typical for the tumour microenvironment almost 90% of the drug was released in a relatively short time. The kinetics models based on different mathematical functions were used to describe the release mechanism of drugs from MWCNTs. Our studies indicated that the best fit of experimental kinetic curves of release has been observed for the Power-law model and the fitted parameters suggest that the drug release mechanism of DOX from MWCNTs is controlled by Fickian diffusion. Molecular dynamics simulations, on the other hand, have shown that in a neutral pH solution, which is close to the blood pH, the release process does not occur keeping the aggregation level constant. The presented studies have shown that MWCNTs are promising carriers of anticancer drugs that, depending on the surface modification, can exhibit different adsorption mechanisms and release.
Topics: Antineoplastic Agents; Doxorubicin; Drug Delivery Systems; Drug Liberation; Hydrogen-Ion Concentration; Kinetics; Molecular Dynamics Simulation; Nanotubes, Carbon; Spectrum Analysis, Raman
PubMed: 34769431
DOI: 10.3390/ijms222112003 -
Molecules (Basel, Switzerland) Sep 2022The use of smart nanocarriers that can modulate therapeutic release aided by biological cues can prevent undesirable cytotoxicity caused by the premature release of...
The use of smart nanocarriers that can modulate therapeutic release aided by biological cues can prevent undesirable cytotoxicity caused by the premature release of cytotoxic drugs during nanocarrier circulation. In this report, degradable nanocarriers based on pH/reduction dual-responsive nanogels were synthesized to encapsulate doxorubicin hydrochloride (DOX) and specifically boost the release of DOX in conditions characteristic of the cancer microenvironment. Nanogels containing anionic monomer 2-carboxyethyl acrylate (CEA) and '-bis(acryloyl)cystamine (CBA) as a degradable crosslinker have been successfully synthesized via photoinitiated free radical polymerization. The loading process was conducted after polymerization by taking advantage of the electrostatic interaction between the negatively charged nanogels and the positively charged DOX. In this case, a high drug loading capacity (DLC) of up to 27.89% was achieved. The entrapment of DOX into a nanogel network could prevent DOX from aggregating in biological media at DOX concentrations up to ~160 µg/mL. Anionic nanogels had an average hydrodynamic diameter (d) of around 90 nm with a negative zeta (ζ) potential of around -25 mV, making them suitable for targeting cancer tissue via the enhanced permeation effect. DOX-loaded nanogels formed a stable dispersion in different biological media, including serum-enriched cell media. In the presence of glutathione (GSH) and reduced pH, drug release was enhanced, which proves dual responsivity. An in vitro study using the HCT 116 colon cancer cell line demonstrated the enhanced cytotoxic effect of the NG-CBA/DOX-1 nanogel compared to free DOX. Taken together, pH/reduction dual-responsive nanogels show promise as drug delivery systems for anticancer therapy.
Topics: Antineoplastic Agents; Carcinoembryonic Antigen; Cystamine; Doxorubicin; Drug Carriers; Drug Liberation; Glutathione; Hydrogen-Ion Concentration; Nanogels; Polyethylene Glycols; Polyethyleneimine
PubMed: 36144713
DOI: 10.3390/molecules27185983 -
Journal of Pharmaceutical and... Jan 2021In the present work, an innovative electrochemical sensor was fabricated based on poly toluidine blue modified glassy carbon electrode (PTB-GCE). So, PTB-GCE was used...
In the present work, an innovative electrochemical sensor was fabricated based on poly toluidine blue modified glassy carbon electrode (PTB-GCE). So, PTB-GCE was used for the detection and determination of doxorubicin hydrochloride (DOX) in cell lysate, and whole human plasma samples. PTB could enhance the rate of electrochemical reaction for the electro oxidation and detection of DOX in real samples. Cyclic voltammetry (CV) technique was used for the electro polymerization of toluidine blue on the surface of GCE with the applied potential ranging from -0.6 to 0.2 V. The sensor construction steps were approved by field emission scanning electron microscopy (FE-SEM), Energy dispersive X-ray spectroscopy (EDX) and electrochemical methods. Also, CV results indicated that the DOX is oxidized via two electrons and two protons process at the optimum pH of 6.5 using PTB modified GCE. Under optimized conditions, differential pulse voltammetry (DPV) technique response exhibited linear relationship between the oxidative peak current and concentration of DOX in the range of 17 nM - 8.6 μM with low limit of quantification (LLOQ) of 17 nM for untreated and treated human plasma samples. Also, determination of DOX in MDA-MB-231 and 4T1cell lysates were performed based on its direct electrochemical oxidation on PTB-GCE. Finally, analytical validation of DOX in human bio-fluids using FDA guideline were done successfully. Results suggested that the proposed electrochemical sensor can be used to the sensitive and selective determination of DOX in biological samples. The interaction results of DOX with cancer cells indicate the developed probe can easily detect candidate drug in cancer cells with high accuracy. To the best of our knowledge this is the first report of the determination of DOX based on the direct electrochemical oxidation on PTB-GCE and determination in MDA-MB-231 and 4T1 cell lysates. It is anticipated that this research open new horizons on the design of new class of electrochemical sensors for determination drugs, and therapeutic drug monitoring (TDM) in human bio-fluids.
Topics: Carbon; Doxorubicin; Electrochemical Techniques; Electrodes; Humans; Limit of Detection; Pharmaceutical Preparations
PubMed: 33120307
DOI: 10.1016/j.jpba.2020.113701 -
Drug Delivery Dec 2021Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While...
Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content of intracellular targets and boost the antitumor effect of DOX, a novel biotinylated hyaluronic acid-guided dual-functionalized CaCO-based drug delivery system (DOX@BHNP) with target specificity and acid-triggered drug-releasing capability was synthesized. The ability of the drug delivery system on enriching DOX in mitochondria and nucleus, which further cause significant tumor inhibition, were investigated to provide a more comprehensive understanding of this CaCO-based drug delivery system. After targeted endocytosis by tumor cells, DOX could release faster in the weakly acidic lysosome, and further enrich in mitochondria and nucleus, which cause mitochondrial destruction and nuclear DNA leakage, and result in cell cycle arrest and cell apoptosis. Virtually, an effective tumor inhibition was observed and . More importantly, the batch-to-batch variation of DOX loading level in the DOX@BHNP system is negligible, and no obvious histological changes in the main organs were observed, indicating the promising application of this functionalized drug delivery system in cancer treatment.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Doxorubicin; Drug Carriers; Drug Liberation; Hyaluronic Acid; Hydrogen-Ion Concentration; Membrane Potential, Mitochondrial; Mice; Nanoparticles; Xenograft Model Antitumor Assays
PubMed: 34668829
DOI: 10.1080/10717544.2021.1986602 -
Nanomedicine (London, England) Feb 2023Folate-targeted Pluronic™ F-127/poly(lactic acid) (FA-F127-PLA) polymersomes were used as codelivery carriers of doxorubicin hydrochloride (DOX) and paclitaxel (PTX)...
Folate-targeted Pluronic™ F-127/poly(lactic acid) (FA-F127-PLA) polymersomes were used as codelivery carriers of doxorubicin hydrochloride (DOX) and paclitaxel (PTX) to achieve a targeted synergistic antitumor effect. The cytotoxicity of PTX/DOX polymersomes against OVCAR-3 cells was determined by methyl thiazolyl tetrazolium assay. The cellular uptake of PTX/DOX polymersomes was examined by HPLC and micro-bicinchoninic acid techniques. The polymersomes showed a bilayer core-shell structure with negative charge and good dispersion. PTX/DOX polymersomes with a mass ratio of PTX to DOX of 1:5 showed the best synergistic effect and the highest cellular uptake. FA-F127-PLA polymersomes have the great promise for codelivery of multiple chemotherapeutics to achieve a targeted antitumor synergistic effect.
Topics: Humans; Female; Paclitaxel; Folic Acid; Apoptosis; Cell Line, Tumor; Ovarian Neoplasms; Doxorubicin; Polyesters; Drug Carriers; Drug Delivery Systems
PubMed: 37166001
DOI: 10.2217/nnm-2022-0212 -
Scientific Reports Aug 2023A new series of 7-substituted coumarin scaffolds containing a methyl ester moiety at the C-position were synthesized and tested for their in vitro anti-proliferative...
A new series of 7-substituted coumarin scaffolds containing a methyl ester moiety at the C-position were synthesized and tested for their in vitro anti-proliferative activity against MCF-7 and MDA-MB-231 breast cancer cell lines using Doxorubicin (DOX) as reference. Compounds 2 and 8 showed noticeable selectivity against MCF-7 with IC = 6.0 and 5.8 µM, respectively compared to DOX with IC = 5.6 µM. Compounds 10, 12, and 14 exhibited considerable selectivity against Estrogen Negative cells with IC = 2.3, 3.5, and 1.9 µM, respectively) compared to DOX with (IC = 7.3 µM). The most promising compounds were tested as epidermal growth factor receptor and aromatase (ARO) enzymes inhibitors using erlotinib and exemestane (EXM) as standards, respectively. Results proved that compound 8 elicited the highest inhibitory activity (94.73% of the potency of EXM), while compounds 10 and 12 displayed 97.67% and 81.92% of the potency of Erlotinib, respectively. Further investigation showed that the promising candidates 8, 10, and 12 caused cell cycle arrest at G0-G1 and S phases and induced apoptosis. The mechanistic pathway was confirmed by elevating caspases-9 and Bax/Bcl-2 ratio. A set of in silico methods was also performed including docking, bioavailability ADMET screening and QSAR study.
Topics: Erlotinib Hydrochloride; Antineoplastic Agents; Doxorubicin; Aromatase Inhibitors; Coumarins; Neoplasms
PubMed: 37591917
DOI: 10.1038/s41598-023-40232-3 -
International Journal of Molecular... Sep 2022Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a...
Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that enables near infrared photothermal heating, and doxorubicin hydrochloride (DOX) as a chemotherapeutic drug. We hypothesize that milliseconds pulsed laser irradiation results in rapid heating and photo-triggered release of DOX, providing a dual photo-chemo therapeutic mechanism for tumor destruction. Additionally, the surface of the nanoparticles is functionalized with folate to target the folate receptor-α on tumor cells to further enhance the therapeutic efficacy. Using non-contract infrared radiometry and absorption spectroscopy, we have characterized the photothermal response and photostability of the nanoparticles to pulsed laser irradiation. Our in vitro studies show that these nanoparticles can mediate photo-chemo killing of SKOV3 ovarian cancer cells when activated by pulsed laser irradiation. We further demonstrate that this dual photo-chemo therapeutic approach is effective in reducing the volume of tumor implants in mice and elicits an apoptotic response. This treatment modality presents a promising approach in destruction of small tumor nodules.
Topics: Animals; Cell Line, Tumor; Doxorubicin; Erythrocytes; Folic Acid; Hyperthermia, Induced; Indocyanine Green; Lasers; Mice; Nanoparticles; Neoplasms; Phototherapy
PubMed: 36142205
DOI: 10.3390/ijms231810295 -
Dalton Transactions (Cambridge, England... Feb 2018A facile methodology is presented to construct a multifunctional nanocomposite that integrates photothermal therapy and specific drug release into a single...
A facile methodology is presented to construct a multifunctional nanocomposite that integrates photothermal therapy and specific drug release into a single nanostructure. Firstly, magnetic FeO@polydopamine core-shell nanoparticles (FeO@PDA) were synthesized via a reversed-phase microemulsion approach. By varying the amount of DA, FeO@PDA with a particle size of 28-38 nm can be obtained. To further ensure the monodispersity, biocompatibility and specific uptake, PEG and lactobionic acid (LA) were grafted onto FeO@PDA (LA-FeO@PDA-PEG), whose fast photothermal conversion is derived by the combination of FeO and PDA with high near infrared (NIR) absorption. Then, doxorubicin hydrochloride (DOX) was adopted as the typical anticancer drug, which was loaded onto LA-FeO@PDA-PEG via electrostatic and π-π stacking interaction. The release kinetics investigation further demonstrated the acid/heat-triggered DOX release. HepG2 cells (hepatocellular cell line) were used as the target cancer cells, and the fast uptake was due to the nanoparticle size and abundant asialoglycoprotein receptors on HepG2 cells. Besides, an external magnetic field also can improve the uptake, especially when the magnet is placed at the bottom of the cell disk. The enhanced specific cytotoxicity toward HepG2 cells was also ascribed to the synergistic effect of chemo- and photothermal therapy. Based on the novel properties, the LA-FeO@PDA-PEG-DOX nanocomposite showed its potential application in hepatocyte therapy.
Topics: Biological Transport; Chemistry Techniques, Synthetic; Disaccharides; Doxorubicin; Drug Carriers; Drug Liberation; Hep G2 Cells; Humans; Indoles; Magnetite Nanoparticles; Particle Size; Phototherapy; Polyethylene Glycols; Polymers
PubMed: 29379913
DOI: 10.1039/c7dt04080f