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Materials Science & Engineering. C,... Jan 2021Nanogel based on polysaccharides has attracted the tremendous interest due to its unique performance as drug carrier for in vivo release. In this work, the...
Nanogel based on polysaccharides has attracted the tremendous interest due to its unique performance as drug carrier for in vivo release. In this work, the multi-responsive nanogels were developed based on the tailor-modified sugarcane bagasse cellulose (SBC). In the presence of crosslinking agent cystamine bisacrylamide (CBA), the in-situ free radical copolymerization of methacrylated monocarboxylic sugarcane bagasse cellulose (MAMC-SBC) and N-isopropylacrylamide (NIPAM) in aqueous phase was conducted, thus leading to redox, pH and thermal-responsive nanogels. The results obtained from FT-IR, SEM and particle sizer showed that the nanogels were highly stable with the desired particle size ranging from 90 to 180 nm and contained targeted polymeric segments and linkage for multi-responsivity. Doxorubicin hydrochloride (DOX) as a model drug was effectively loaded into the nanogels, partly driven by strong electrostatic association; and the loading efficiency reached up to 82.7%. Moreover, the drug release could be readily manipulated by the addition of reducing agent, pH and temperature, which is attributed to the multi-responsive behavior of nanogels as carrier and synergetic effects. The performance of nanogels was also governed by the ratio of reactive MAMC-SBC and NIPAM during polymerization; and the ratio at 1:1(wt) led to the optimal structure of nanogels.
Topics: Cellulose; Doxorubicin; Drug Carriers; Hydrogen-Ion Concentration; Nanogels; Saccharum; Spectroscopy, Fourier Transform Infrared
PubMed: 33254977
DOI: 10.1016/j.msec.2020.111357 -
Carbohydrate Polymers Aug 2023Breast cancer is one of the most threatening cancers that poses a great risk to women's health. The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in...
Breast cancer is one of the most threatening cancers that poses a great risk to women's health. The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in the treatment of breast cancer. However, the cytotoxicity of DOX has always been an urgent challenge to be solved. In this study, we report an alternative drug delivery system delivering DOX for reducing its physiological toxicity by using the yeast β-glucan particle (YGP) with a hollow and porous vesicle structure. Briefly, amino groups were grafted onto the surface of YGP with the silane coupling agent, then the oxidized hyaluronic acid (OHA) was attached by Schiff base reaction to get HA-modified YGP (YGP@N=C-HA), finally DOX was encapsulated into YGP@N=C-HA to get DOX-loaded YGP@N=C-HA (YGP@N=C-HA/DOX). In vitro release experiments exhibited the pH-responsive DOX release from YGP@N=C-HA/DOX. Cell experiments displayed that YGP@N=C-HA/DOX had good killing effect on both MCF-7 and 4T1 cells and could be internalized into these cells through CD44 receptors, showing targetability to cancer cells. Furthermore, YGP@N=C-HA/DOX could effectively inhibit tumor growth and reduce the physiological toxicity of DOX. Thus, the YGP-based vesicle provides an alternative strategy for lowering the physiological toxicity of DOX in the medical treatment of breast cancer.
Topics: Female; Humans; Breast Neoplasms; Hyaluronic Acid; Saccharomyces cerevisiae; beta-Glucans; Doxorubicin; Drug Delivery Systems; Nanoparticles; MCF-7 Cells
PubMed: 37173014
DOI: 10.1016/j.carbpol.2023.120907 -
Journal of Biochemical and Molecular... Jun 2020Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer-related death worldwide. The doxorubicin hydrochloride is one of...
Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer-related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co-administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox-Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL-2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox-Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox-Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration- and time-dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox-Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox-Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.
Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 9; Cell Line, Tumor; Cell Movement; Cell Survival; Curcuma; Curcumin; Doxorubicin; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Spheroids, Cellular; Stomach Neoplasms; bcl-2-Associated X Protein
PubMed: 32128952
DOI: 10.1002/jbt.22486 -
International Journal of Molecular... Feb 2022In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin...
In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin hydrochloride in triple negative breast cancer cell lines. A phosphatidylcholine lipid film was hydrated with a solution of oxidized hyaluronic acid and doxorubicin, chosen as model drug, followed by a crosslinking reaction with cystamine hydrochloride. The obtained spherical nanoparticles (mean diameter of 30 nm) were found to be efficiently internalized in cancer cells by a receptor-mediated endocytosis process, and to modulate the drug release depending on the pH and redox potential of the surrounding medium. In vitro cytotoxicity assays demonstrated the safety and efficacy of the nanoparticles in enhancing the cytotoxic effect of the free anticancer drug, with the IC values being reduced by two and three times in MDA-MB-468 and MDA-MB-231, respectively. The combination of self-assembled phospholipid molecules with a polysaccharide counterpart acting as receptor ligand, and stimuli-responsive chemical moieties, was carried out on smart multifunctional nanoparticles able to actively target breast cancer cells and improve the in vitro anticancer activity of doxorubicin.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Drug Liberation; Endocytosis; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Hydrogen-Ion Concentration; Lipids; Liposomes; Nanoparticles; Particle Size; Polysaccharides
PubMed: 35216501
DOI: 10.3390/ijms23042386 -
Colloids and Surfaces. B, Biointerfaces Aug 2023Due to the inability of nano-carriers to passively cross the cell membrane, cell penetration enhancers are used to accelerate cytoplasmic delivery of antineoplastic...
HYPOTHESIS
Due to the inability of nano-carriers to passively cross the cell membrane, cell penetration enhancers are used to accelerate cytoplasmic delivery of antineoplastic drugs. In this regard, snake venom phospholipase A2 peptides are known for their ability to destabilize natural and artificial membranes. In this context, functionalized liposomes with peptide pEM-2 should favor the incorporation of doxorubicin and increase its cytotoxicity in HeLa cells compared to free doxorubicin, and doxorubicin encapsulated in non-functionalized liposomes.
EXPERIMENTS
Several characteristics were monitored, including doxorubicin loading capacity of the liposomes, as well as the release and uptake before and after functionalization. Cell viability and half-maximal inhibition concentrations were determined in HeLa cells.
FINDINGS
In vitro studies showed that functionalization of doxorubicin-loaded PC-NG liposomes with pEM-2 not only improved the amount of doxorubicin delivered compared to free doxorubicin or other doxorubicin-containing formulations, but also showed enhanced cytotoxicity against HeLa cells. The PC-NG liposomes loaded with doxorubicin improved treatment efficacy by reducing the IC value and incubation time. This increase in cell toxicity was directly related to the concentration of pEM-2 peptide bound to the liposomes. We conclude that the cytotoxicity observed in HeLa cells due to the action of doxorubicin was strongly favored when encapsulated in synthetic liposomes and functionalized with the pEM-2 peptide.
Topics: Humans; Liposomes; HeLa Cells; Doxorubicin; Peptides; Drug Delivery Systems; Cell Line, Tumor
PubMed: 37379702
DOI: 10.1016/j.colsurfb.2023.113420 -
Advanced Drug Delivery Reviews Nov 2021We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be... (Review)
Review
We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.
Topics: Animals; Antibiotics, Antineoplastic; Doxorubicin; Drug Delivery Systems; Drug Development; Drug Liberation; Humans; Hyperthermia; Hyperthermia, Induced; Polyethylene Glycols
PubMed: 34555486
DOI: 10.1016/j.addr.2021.113985 -
FEBS Open Bio Jan 2022DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor in the CUL4-DDB1 E3 ligase, and its expression is associated with the prognosis of certain cancers....
DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor in the CUL4-DDB1 E3 ligase, and its expression is associated with the prognosis of certain cancers. In the present study, we report evidence that DCAF13 is aberrantly overexpressed in human breast cancer and its expression is positively associated with cancer progression. Further analysis showed that the DCAF13 expression level is significantly higher in triple-negative breast cancer compared to non-triple-negative breast cancer, indicating a positive correlation between its expression and the aggressiveness of breast cancer. Subsequent studies revealed that DCAF13 regulates cancer cell migration, invasion and epithelial-mesenchymal transition in human breast cancer, whereas it has no significant impact on breast cancer cell proliferation, cell cycle progressionor apoptosis. Taken together, our results demonstrate that DCAF13 promotes the epithelial-mesenchymal transition in human breast cancer cells, indicating an involvement in breast cancer metastasis. Furthermore, we report that doxorubicin, a widely used chemotherapy drug, increases DCAF13 expression in breast cancer cells, leading to enhanced cancer cell migration and invasion. These results suggest that doxorubicin chemotherapy may increase the risk of metastasis of drug-resistant breast cancer cells, and future therapeutics targeting DCAF13 may help reduce the risk, especially for patients undergoing chemotherapy.
Topics: Cell Movement; Doxorubicin; Epithelial-Mesenchymal Transition; Humans; RNA-Binding Proteins; Triple Negative Breast Neoplasms
PubMed: 34775691
DOI: 10.1002/2211-5463.13330 -
Physical Chemistry Chemical Physics :... Nov 2022Anthracycline doxorubicin hydrochloride (DX) is a positively charged fluorescent drug, which in water self-associates into non-fluorescent antiparallel dimers upon...
Anthracycline doxorubicin hydrochloride (DX) is a positively charged fluorescent drug, which in water self-associates into non-fluorescent antiparallel dimers upon increasing concentration and/or ionic strength. The positive charge of DX allows for complexation with negatively charged polymers and drug carriers. The fluorescence of DX following complexation with polyanion polystyrene sulfonate (PSS) is studied here. The fluorescence emission of DX decreases in the presence of PSS, being almost completely quenched when the ratio () of PSS monomers-to-DX molecules is larger than 10. Increasing values over 30 results in a progressive recovery of fluorescence. The circular dichroism of PSS-DX complexes shows inverted characteristic bands of DX dimers suggesting the presence of parallel dimers at a concentration of DX below dimerization in water. Molecular dynamics studies corroborate a preferential orientation of DX into parallel dimers when interacting with PSS and show that DX molecules interact with a binding pocket of PSS monomers rather than with one single monomer. Increasing the ionic strength results in a recovery of fluorescence without an apparent release of DX from the PSS-DX complex as shown by DOSY NMR. PSS acts as a template for concentrating DX, triggering dimerisation and orienting DX molecules with their charged groups facing the negatively charged PSS monomers.
Topics: Dimerization; Polystyrenes; Doxorubicin; Polymers; Water
PubMed: 36263861
DOI: 10.1039/d2cp02714c -
International Journal of Biological... May 2024Spray-dried niobium oxide coated with chitosan-activated carbon (NIC) was synthesized and used to remove doxorubicin hydrochloride and crystal violet from aqueous...
Removal of doxorubicin hydrochloride and crystal violet from aqueous solutions using spray-dried niobium oxide coated with chitosan-activated carbon: Experimental and DFT calculations.
Spray-dried niobium oxide coated with chitosan-activated carbon (NIC) was synthesized and used to remove doxorubicin hydrochloride and crystal violet from aqueous solutions under different parameters such as solution pH (2, 4, 6, and 8), contact time (1 to 9 h), initial concentration (20 to 200 mg L), and competing ions (0.1 M of CaCl and NaCl). The addition of 5 % chitosan-activated carbon to the matrix of niobium oxide slightly increased the specific surface area from 26 to 30 m g, with the introduction of a carboxylic functional group. This led to an increase in the amount of adsorbed doxorubicin hydrochloride (DOH) from 30 to 44 mg g and that of crystal violet (CV) from 15 to 32 mg g from the initial respective 100 mg L at pH 8. The data from the concentration study fitted into Liu isotherm having adsorption capacity of 128 and 57 mg g for DOH and CV respectively, while pseudo first and second order are more suitable for adsorption kinetics. The additional functional groups on the IR spectrum of NIC after the adsorption of DOH and CV confirmed the interaction between NIC and the adsorbates' molecules. The mechanism of adsorption was supported by DFT calculations.
Topics: Chitosan; Doxorubicin; Adsorption; Niobium; Gentian Violet; Hydrogen-Ion Concentration; Charcoal; Kinetics; Water Pollutants, Chemical; Density Functional Theory; Oxides; Water; Solutions; Water Purification
PubMed: 38552682
DOI: 10.1016/j.ijbiomac.2024.131158 -
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