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Colloids and Surfaces. B, Biointerfaces Oct 2022The specific characteristics of the tumor microenvironment (TME) and monotherapy always lead to poor therapy effects for tumors. Hereby, we have developed a smart...
The specific characteristics of the tumor microenvironment (TME) and monotherapy always lead to poor therapy effects for tumors. Hereby, we have developed a smart multifunctional theranostic agent-SSMID (Se@SiO@MnO-ICG/DOX) nanocomposites (NCs) that could intelligently respond to the TME for enhanced chemotherapy/photothermal/chemodynamic therapy guided by magnetic resonance imaging (MRI). The SSMID NCs were composed of indocyanine green (ICG) and doxorubicin hydrochloride (DOX) co-loaded porous Se@SiO @MnO. Under the specific conditions of the TME (slightly acidic, HO and GSH overexpression), the MnO NPs were specifically decomposed and then SSMID released Mn, DOX and Se, which played roles in chemodynamic therapy (CDT), chemotherapy, protecting normal tissues and inhibiting tumor cells by modulating reactive oxygen species (ROS), respectively. MnO reacted with glutathione (GSH) and HO to generate O and Mn, which alleviated tumor hypoxia to improve chemotherapy and depleted GSH to enhance oxidative stress for chemodynamic therapy. More importantly, SSMID NCs could simultaneously exert the photothermal therapy (PTT) effect with near-infrared laser irradiation and promote the release of Mn and DOX to achieve enhanced chemotherapy/chemodynamic therapy. In addition, the released Mn could be used as a T1-weighted MRI contrast agent to monitor tumor location. The SSMID NCs exhibited a pronounced tumor growth inhibitory effect and promising biological safety, which develop a new method to rationally design nano-theranostic agents with enhanced performance for anti-tumor.
Topics: Cell Line, Tumor; Contrast Media; Doxorubicin; Glutathione; Humans; Hydrogen Peroxide; Indocyanine Green; Manganese Compounds; Neoplasms; Oxides; Photothermal Therapy; Reactive Oxygen Species; Silicon Dioxide; Theranostic Nanomedicine; Tumor Microenvironment
PubMed: 35961116
DOI: 10.1016/j.colsurfb.2022.112750 -
Journal of Separation Science Feb 2023While histone deacetylase inhibitors, such as vorinostat, demonstrate a significant effect against hematological cancers, their application for solid tumor treatment is...
Box-Behnken assisted development and validation of high-performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles.
While histone deacetylase inhibitors, such as vorinostat, demonstrate a significant effect against hematological cancers, their application for solid tumor treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g., doxorubicin) enhances the antitumoral action of both drugs against tumors. We developed a high-performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles designed to provide the parenteral administration of both drugs and increase their safety profile. We performed separation on Nucleodur C-18 Gravity column with a mixture of 10 mM potassium dihydrogen phosphate buffer pH 3.9:ACN (90:10 v/v) as mobile phase at 240 nm. The method was linear within the concentration range of 4.2-52.0 μg/ml for both drugs with limits of detection and quantification of 3.5 and 10.7 μg/ml for doxorubicin and 2.5 and 7.7 μg/ml for vorinostat, respectively. The method was precise and accurate over the concentration range of analysis. Drug loading was 5.4% for doxorubicin and 0.8% for vorinostat. Degradation of doxorubicin after irradiation was less than 5%, while the amount of vorinostat decreased at 88% under the same conditions. Thus, the validated method could be adopted for routine simultaneous analysis of doxorubicin and vorinostat in polymeric nanoparticles.
Topics: Humans; Vorinostat; Chromatography, High Pressure Liquid; Doxorubicin; Histone Deacetylase Inhibitors; Neoplasms; Pharmaceutical Preparations; Nanoparticles
PubMed: 36427291
DOI: 10.1002/jssc.202200731 -
International Journal of Pharmaceutics May 2020Layer-by-layer (LbL) assembled poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) microcapsules were designed to incorporate gold nanorods (NRs) and...
Layer-by-layer (LbL) assembled poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) microcapsules were designed to incorporate gold nanorods (NRs) and co-encapsulate and release two drugs for cancer therapy. Calcium carbonate (CaCO) microparticles modified with preformed NRs were used as sacrificial templates for the fabrication of hollow PAH/PMA/NR capsules incorporated with NRs. The hollow capsules were found to be 4.5 ± 0.5 µm in size and appeared with uniformly distributed NRs in the interior of the capsules. The morphology of the capsules transformed from pore free continuous structure to porous structure under laser light irradiation at 808 nm and 0.5 W cm. The encapsulation experiments showed that the hydrophilic drug (doxorubicin hydrochloride, Dox) was encapsulated in the interior of the capsules while the hydrophobic drug (nimbin, NB) was entrapped in the porous polymeric network of the layer components. The encapsulation efficiency was found to be 30% for both Dox and NB. The release experiments showed an initial burst release followed by sustained release up to 3 h. Notably, the release was completed within 30 min under NIR irradiation at 808 nm. The estimated IC values against THP-1 cells were 75 and 1.8 µM for NB and Dox, respectively. The dual drug loaded capsules showed excellent anticancer activity against THP-1 cells under NIR light exposure in in-vitro experiments. Thus, such remotely addressable dual-drug loaded capsules with the provision for encapsulation of natural drugs demonstrate high potential for use as theranostics in cancer therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capsules; Cell Death; Doxorubicin; Drug Carriers; Drug Compounding; Drug Liberation; Gold; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; Leukemia, Monocytic, Acute; Limonins; Nanotubes; Photothermal Therapy; Polyamines; Polymethacrylic Acids; Porosity; Proof of Concept Study; THP-1 Cells
PubMed: 32315747
DOI: 10.1016/j.ijpharm.2020.119350 -
Langmuir : the ACS Journal of Surfaces... Nov 2019We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted...
We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH = 7.4) to cubic (pH = 6.8) to emulsified microemulsion (pH = 5.3) phase transition with a therapeutic application in cancer inhibition. BJO is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an antitumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need for safe delivery carriers. Here, pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein-oleic acid-BJO-DOX) systems are determined by synchrotron small-angle X-ray scattering and the Langmuir film balance technique. The nanocarrier assemblies display good physical stability in the studied pH range and adequate particle sizes and ζ-potentials. Their interaction with model lipid membrane interfaces is enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO-DOX dual-loaded pH-switchable liquid crystalline nanoparticles are performed on the human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines exhibit enhanced antitumor efficacy. The performed preliminary studies suggest a potential reversal of the resistance of the MCF-7/DOX cells to DOX. These results highlight the necessity for further understanding the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, and emulsified microemulsion inner organizations for therapeutic outcomes.
Topics: Antibiotics, Antineoplastic; Apoptosis; Brucea; Cell Proliferation; DNA Replication; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Screening Assays, Antitumor; Humans; Hydrogen-Ion Concentration; Lipids; MCF-7 Cells; Nanoparticles; Particle Size; Plant Oils; Seeds; Surface Properties
PubMed: 31635451
DOI: 10.1021/acs.langmuir.9b02257 -
Journal of Fluorescence Jan 2021Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer...
Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer treatment. The use of polymers such as Pluronic is being studied widely for the formulation of doxorubicin hydrochloride. However, the basic understanding of the physicochemical properties of pluronic micelles in presence of doxorubicin hydrochloride is a very essential topic of study. Doxorubicin hydrochloride is fluorescent; this helped us to study its sensitivity towards the Pluronic microenvironment using the fluorescence technique. In this work, the interaction and place of location of doxorubicin hydrochloride in Pluronic F127 and P123 micelles has been studied extensively using steady-state fluorescence intensity, dynamic fluorescence lifetime, quenching studies, dynamic light scattering, and zeta potential measurements, at different Pluronic concentrations. Using a fluorescence quenching experiment, doxorubicin hydrochloride was found to reside near the hydrophilic PEO corona region of the Pluronic micelles. For both the Pluronic, in the concentration range of study, the micellar size was found to be below 30 nm; this may have a greater advantage for various applications.
Topics: Antineoplastic Agents; Doxorubicin; Fluorescence; Hydrophobic and Hydrophilic Interactions; Micelles; Poloxalene; Polyethylenes; Polypropylenes
PubMed: 33037527
DOI: 10.1007/s10895-020-02630-y -
Molecular Pharmaceutics Aug 2023Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability...
Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.
Topics: Humans; Female; Doxorubicin; Breast Neoplasms; Liposomes; Paclitaxel; Calcium; Phosphates; Cell Line, Tumor; Drug Delivery Systems; Nanoparticles; Hydrogen-Ion Concentration
PubMed: 37384449
DOI: 10.1021/acs.molpharmaceut.3c00015 -
Small (Weinheim An Der Bergstrasse,... Aug 2022Ultrasmall gold nanoparticles (2 nm) easily penetrate the membranes of intestinal murine epithelial cells (MODE-K) and colorectal cancer cells (CT-26). They are also...
Ultrasmall gold nanoparticles (2 nm) easily penetrate the membranes of intestinal murine epithelial cells (MODE-K) and colorectal cancer cells (CT-26). They are also taken up by 3D spheroids (400 µm) of these cell types and primary gut organoids (500 µm). In contrast, dissolved dyes are not taken up by any of these cells or 3D structures. The distribution of fluorescent ultrasmall gold nanoparticles inside cells, spheroids, and gut organoids is examined by confocal laser scanning microscopy. Nanoparticles conjugated with the cytostatic drug doxorubicin and a fluorescent dye exhibit significantly greater cytotoxicity toward CT-26 tumor spheroids than equally concentrated dissolved doxorubicin, probably because they enter the interior of a spheroid much more easily than dissolved doxorubicin. Comprehensive analyses show that the cellular uptake of ultrasmall gold nanoparticles occurs by different endocytosis pathways.
Topics: Animals; Doxorubicin; Gold; Humans; Metal Nanoparticles; Mice; Neoplasms; Spheroids, Cellular
PubMed: 35712760
DOI: 10.1002/smll.202201167 -
ACS Applied Materials & Interfaces Dec 2021Nanomaterial selection is critical for photoelectrochemical (PEC) sensing. In this report, a novel cathodic photoelectrochemical (PEC) strategy was proposed for the...
Nanomaterial selection is critical for photoelectrochemical (PEC) sensing. In this report, a novel cathodic photoelectrochemical (PEC) strategy was proposed for the detection of doxorubicin hydrochloride (Dox) and gentamicin sulfate (CN). The photocathode was synthesized by noncovalently coupling cadmium sulfide (CdS) to the porphyrin-derived metal-organic framework (CdS@PCN-224). This type of assembly created a pleasant interface for the combination of doxorubicin hydrochloride and gentamicin sulfate, resulting in a good CdS@PCN-224 donor-acceptor system. When compared to a single optoelectronic material, its photocurrent is enhanced by unprecedented nine times. This research could pave the way for the realization of PCN-224's enormous potential in PEC sensing.
Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Biomimetic Materials; Biosensing Techniques; Cadmium Compounds; Doxorubicin; Electrochemical Techniques; Gentamicins; Materials Testing; Metal-Organic Frameworks; Molecular Structure; Particle Size; Photochemical Processes; Sulfides
PubMed: 34807581
DOI: 10.1021/acsami.1c19481 -
Colloids and Surfaces. B, Biointerfaces Feb 2020Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a...
Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, d-glucosamine hydrochloride) and non-ionized (Paclitaxel (PTX)) drugs were examined. Furthermore, the relationship between the bipolar level of DOX solution (contributing to H-bonding of DOX and GO) and the amount of DOX loading was investigated. The DOX showed higher loading (>3 times) than PTX, as anticancer drugs. Since both DOX and PTX possess aromatic structures, the higher loading of DOX was assigned to its positive partial charge and ionized nature. Accordingly, other drugs (having positive partial charge and ionized nature, but no aromatic structure) such as Amikacin sulfate and d-glucosamine hydrochloride presented higher loading than PTX. These results indicated that although the π-π interactions induced by aromatic structures are important in drug loading, the electrostatic interaction of ionized drugs with GO (especially through H-bonding) is the dominant mechanism. DOX-loaded GANPs showed high pH-sensitive release (equivalent to the carrier weight) after 5 days, which can indicate benefits in tumor cell acidic microenvironments in-vivo.
Topics: Amikacin; Antineoplastic Agents; Doxorubicin; Drug Liberation; Gels; Glucosamine; Graphite; Hydrogen-Ion Concentration; Nanoparticles; Paclitaxel; Particle Size; Surface Properties
PubMed: 31846894
DOI: 10.1016/j.colsurfb.2019.110712 -
Environmental Science and Pollution... May 2022The purpose of this investigation was to analyze the performance of magnetite graphene oxide modified with β-cyclodextrin (GO@FeO@β-CD) for adsorption of methotrexate...
The purpose of this investigation was to analyze the performance of magnetite graphene oxide modified with β-cyclodextrin (GO@FeO@β-CD) for adsorption of methotrexate (MTX) and doxorubicin (DOX) from aqueous solutions. Characterization of GO@FeO@β-CD was carried out using some methods. The perfect conditions for the adsorption of MTX and DOX were 7.0, 45 min, 20 mg, and 25 °C for solution pH, contact time, adsorbent dose, and temperature, respectively, with removal efficiency values of 97.8% and 98.5% for MTX and DOX, respectively. The adsorption kinetic of MTX and DOX via GO@FeO@β-CD followed pseudo second-order (PSO) model, while the adsorption isotherm obeyed Langmuir model by monolayer adsorption with maximum adsorption capacities of 198.5 and 204.5 mg g for MTX and DOX, respectively. Therefore, it could be argued that HCl and 0.1 mol L NaOH would reflect adequate elution properties for GO@FeO@β-CD recovery.
Topics: Adsorption; Doxorubicin; Ferrosoferric Oxide; Graphite; Hydrogen-Ion Concentration; Kinetics; Methotrexate; Water; Water Pollutants, Chemical; Water Purification; beta-Cyclodextrins
PubMed: 35044605
DOI: 10.1007/s11356-022-18725-x