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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 -
Chemical Biology & Drug Design Jul 2017θ-defensins belong to the family of host defence peptides. They are the only known example of cyclic polypeptides in animal proteomes. This study presents the synthesis...
θ-defensins belong to the family of host defence peptides. They are the only known example of cyclic polypeptides in animal proteomes. This study presents the synthesis of simplified θ-defensin analogues with pairs of cysteine replaced either by alanine, leucine or serine residues. Cytotoxicity tests were performed on human mammary epithelial (HB2) and breast cancer (SKBR3, MDA-MB-231) cell lines to determine whether peptides are selectively targeting cancer cells. The effect of these peptides was also evaluated in 3D Matrigel cultures, which are based on extracellular matrix components and therefore closely represent in vivo conditions. Finally, to determine whether analogues are able to sensitize MDA-MB-231 triple-negative breast cancer cells to chemotherapeutics, we co-administrated peptides with cisplatin or doxorubicin hydrochloride also in 3D Matrigel cultures. Additionally, cytotoxicity towards peripheral blood mononuclear cells and haemolytic effect were examined for a chosen representative of synthesized compounds. The results showed that positively charged serine-containing θ-defensin derivatives were more cytotoxic towards breast cancer cells (SKBR3, MDA-MB-231) than towards mammary epithelial cells (HB2). Analogues enhanced the effect of cisplatin and doxorubicin hydrochloride on triple-negative breast cancer cell line (MDA-MB-231).
Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Cell Survival; Cisplatin; Defensins; Doxorubicin; Erythrocytes; Hemolysis; Humans; Leukocytes, Mononuclear; Peptides; Serine
PubMed: 28004513
DOI: 10.1111/cbdd.12927 -
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 -
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 -
International Journal of Nanomedicine 2017Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been...
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/miR-375 overcame drug efflux and delivered miR-375 and DOX into MDR HepG2/ADR cells or HCC tissues. MiR-375 delivered by LHD/miR-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of miR-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/miR-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that miR-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of miR-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Animals; Antibiotics, Antineoplastic; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Drug Resistance, Neoplasm; Humans; Lipids; Liver Neoplasms; Mice, Inbred BALB C; MicroRNAs; Nanoparticles; Silicon Dioxide; Tissue Distribution; Xenograft Model Antitumor Assays
PubMed: 28769563
DOI: 10.2147/IJN.S135306 -
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 -
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