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Journal of Biomaterials Applications Oct 2021Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting...
Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
Topics: Aspartic Acid; Curcumin; Doxorubicin; Drug Delivery Systems; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Nanoparticles; Neoplasms; Particle Size; Peptides; Tumor Microenvironment
PubMed: 33509034
DOI: 10.1177/0885328220988071 -
International Journal of Nanomedicine 2023As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with...
Zeolitic Imidazolate Framework (ZIF-8) Decorated Iron Oxide Nanoparticles Loaded Doxorubicin Hydrochloride for Osteosarcoma Treatment - in vitro and in vivo Preclinical Studies.
BACKGROUND
As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.
METHODS
In this study, a FeO@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- FeO@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of FeO@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.
RESULTS
DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p<0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p<0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.
CONCLUSION
In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- FeO@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.
Topics: Animals; Mice; Doxorubicin; Zeolites; Metal-Organic Frameworks; Drug Delivery Systems; Osteosarcoma; Nanoparticles; Bone Neoplasms; Magnetic Iron Oxide Nanoparticles; Drug Carriers
PubMed: 38164268
DOI: 10.2147/IJN.S438771 -
World Journal of Gastroenterology Oct 2016Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative...
Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities.
Topics: Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cost-Benefit Analysis; Doxorubicin; Humans; Liver Neoplasms; Outcome Assessment, Health Care
PubMed: 27833376
DOI: 10.3748/wjg.v22.i40.8853 -
Journal of Oleo Science Oct 2023In this study, we analyzed the properties of amphiphilic alkyldi(methoxy poly(ethylene glycol) (MePEG)350-lactate) phosphates based on ethyl lactate, the monomethyl...
In this study, we analyzed the properties of amphiphilic alkyldi(methoxy poly(ethylene glycol) (MePEG)350-lactate) phosphates based on ethyl lactate, the monomethyl ether of poly(ethylene glycol)350, and alkyldichloro phosphates. Interestingly, these triesters combine two biodegradable bonds, -P(O)-O-C and -C(O)-O-C-, and include hydrophilic (MePEG350-lactate) and hydrophobic (R-aliphatic chain of alcohols) moieties. The properties of these esters resemble those of phospholipids. After being placed in an aqueous solution, they self-assembled. We also determined the effects of ester composition on micelle formation, stability, and size using dynamic light scattering. Solubilization tests using Sudan III or doxorubicin hydrochloride (Dox·HCl) revealed that they could be incorporated into the hydrophobic cores of dodecyl di(MePEG350-lactate) phosphate and hexadecyl di(MePEG350-lactate) phosphate. Notably, dodecyl di(MePEG350-lactate) phosphate was stable for five days, whereas hexadecyl di(MePEG350-lactate) phosphate was stable for seven days in phosphate-buffered saline. Moreover, Dox·HCl release rates from the micelles were approximately 30-40, 70-80, and 90-100% after 1, 5, and 28 d, respectively.
Topics: Micelles; Polyethylene Glycols; Doxorubicin; Phosphates; Lactates; Drug Carriers
PubMed: 37704442
DOI: 10.5650/jos.ess23108 -
Molecules (Basel, Switzerland) Jun 2021Silica nanoparticles (SiO NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto...
Silica nanoparticles (SiO NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto the SiO NPs surfaces. The DOX·HCl loading onto and release from the SiO NPs was monitored via UV-VIS and fluorescence spectra. Alternatively, the zeta potential was also used to monitor and evaluate the DOX·HCl loading process. The results showed that nearly 98% of DOX·HCl was effectively loaded onto the SiO NPs' surfaces by electrostatic interaction. The pH-dependence of the process wherein DOX·HCl release out of DOX·HCl-SiO NPs was investigated as well. For comparison, both the free DOX·HCl molecules and DOX·HCl-SiO NPs were used as the labels for cultured cancer cells. Confocal laser scanning microscopy images showed that the DOX·HCl-SiO NPs were better delivered to cancer cells which are more acidic than healthy cells. We propose that engineered DOX·HCl-SiO systems are good candidates for drug delivery and clinical applications.
Topics: Antineoplastic Agents; Doxorubicin; Drug Carriers; Humans; MCF-7 Cells; Microscopy, Confocal; Nanoparticles; Neoplasms; Silicon Dioxide
PubMed: 34209621
DOI: 10.3390/molecules26133968 -
Pharmacological Research Nov 2022Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a...
Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a high rate of relapse and a very low 5-year survival percentage of less than 25%. CXCR4 is a highly expressed chemokine receptor in multiple types of AML cells and closely associated with the drug resistance and relapse. In this work, we integrate a chemically synthesized CXCR4 antagonistic peptide and doxorubicin using DSPE-mPEG2000 micelles (referred to as M-E5-Dox) that is applied to a very challenging refractory AML mouse model as well as human AML cell lines. Results showed that M-E5-Dox can effectively bind to the CXCR4-expressing AML cells, downregulating the signaling proteins mediated by CXCR4/CXCL12 axis and increasing the cellular uptake of Dox. Importantly, M-E5-Dox remarkably decreases the leukemic cells in the peripheral blood and bone marrow, as well as their infiltration in the spleen and liver of the AML mice, which in turn prolongs the survival significantly. Meanwhile, M-E5-Dox did not increase the cardiotoxicity of Dox. In conclusion, M-E5-Dox harnesses the functions of CXCR4 specific binding and CXCR4 antagonism of the peptide and the tumor cell killing capacity of Dox, which displays significant therapeutic effects and promising translational potentials for the treatment of refractory AML.
Topics: Humans; Mice; Animals; Leukemia, Myeloid, Acute; Doxorubicin; Signal Transduction; Peptides; Recurrence; Receptors, CXCR4
PubMed: 36241000
DOI: 10.1016/j.phrs.2022.106503 -
Lab on a Chip Mar 2024The current challenge in using extracellular vesicles (EVs) as drug delivery vehicles is to precisely control their membrane permeability, specifically in the ability to...
The current challenge in using extracellular vesicles (EVs) as drug delivery vehicles is to precisely control their membrane permeability, specifically in the ability to switch between permeable and impermeable states without compromising their integrity and functionality. Here, we introduce a rapid, efficient, and gentle loading method for EVs based on tonicity control (TC) using a lab-on-a-disc platform. In this technique, a hypotonic solution was used for temporarily permeabilizing a membrane ("on" state), allowing the influx of molecules into EVs. The subsequent isotonic washing led to an impermeable membrane ("off" state). This loading cycle enables the loading of different cargos into EVs, such as doxorubicin hydrochloride (Dox), ssDNA, and miRNA. The TC approach was shown to be more effective than traditional methods such as sonication or extrusion, with loading yields that were 4.3-fold and 7.2-fold greater, respectively. Finally, the intracellular assessments of miRNA-497-loaded EVs and doxorubicin-loaded EVs confirmed the superior performance of TC-prepared formulations and demonstrated the impact of encapsulation heterogeneity on the therapeutic outcome, signifying potential opportunities for developing novel exosome-based therapeutic systems for clinical applications.
Topics: Extracellular Vesicles; MicroRNAs; Exosomes; Cell Communication; Doxorubicin; Drug Delivery Systems
PubMed: 38436394
DOI: 10.1039/d3lc00830d -
International Journal of Pharmaceutics May 2017Drug release from chemoembolization microspheres stimulated by the presence of a chemically reducing environment may provide benefits for targeting drug resistant and...
Drug release from chemoembolization microspheres stimulated by the presence of a chemically reducing environment may provide benefits for targeting drug resistant and metastatic hypoxic tumours. A water-soluble disulfide-based bifunctional cross-linker bis(acryloyl)-(l)-cystine (BALC) was synthesised, characterised and incorporated into a modified poly(vinyl) alcohol (PVA) hydrogel beads at varying concentrations using reverse suspension polymerisation. The beads were characterised to confirm the amount of cross-linker within each formulation and its effects on the bead properties. Elemental and UV/visible spectroscopic analysis confirmed the incorporation of BALC within the beads and sizing studies showed that in the presence of a reducing agent, all bead formulations increased in mean diameter. The BALC beads could be loaded with doxorubicin hydrochloride and amounts in excess of 300mg of drug per mL of hydrated beads could be achieved but required conversion of the carboxylic acid groups of the BALC to their sodium carboxylate salt forms. Elution of doxorubicin from the beads demonstrated a controlled release via ionic exchange. Some formulations exhibited an increase in size and release of drug in the presence of a reducing agent, and therefore demonstrated the ability to respond to an in vitro reducing environment.
Topics: Antibiotics, Antineoplastic; Chemoembolization, Therapeutic; Doxorubicin; Drug Liberation; Hydrogels; Hypoxia; Microspheres
PubMed: 28373099
DOI: 10.1016/j.ijpharm.2017.03.084 -
Journal of Liposome Research Sep 2020Combination therapy with conventional chemotherapeutic drugs strongly demonstrates a good approach to reduce cytotoxicity, resistance, and the dose of the potent...
Combination therapy with conventional chemotherapeutic drugs strongly demonstrates a good approach to reduce cytotoxicity, resistance, and the dose of the potent anticancer drugs. The purpose of this research was to design and characterize liposome incorporating celecoxib (CEL) and doxorubicin hydrochloride (DOX) and investigate the anti-tumor efficacy of this combination on different tumor cells. A simple comparison study had been performed for liposomes formulation using thin-film hydration method and pH-gradient method. HSPC-incorporated liposomes were chosen for encapsulation of both CEL and DOX. The formulations showed small particle size and polydispersity index with high encapsulation efficiency. DOX/CEL liposomes displayed the strongest cytotoxicity against B16 and MGC80-3 cells in comparison to the corresponding drug solutions. By incorporation of both agents, a significant reduction in IC50 from 0.927 to 0.198 µg/ml and from 0.81 to 0.535 µg/ml against B16 cells and MGC80-3 cells, respectively, was observed. CEL also significantly improved the intracellular retention and accumulation of DOX . Our data suggest that the developed liposomal formulation proved to be the most effective formulative strategy as a dual drug delivery system for incorporation of both doxorubicin HCL and CEL and could be considered a useful tool for enhancing the therapeutic efficacy of the anticancer drug.
Topics: Animals; Antineoplastic Agents; Celecoxib; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Screening Assays, Antitumor; Humans; Liposomes; Mice; Particle Size; Structure-Activity Relationship; Surface Properties; Tumor Cells, Cultured
PubMed: 31223044
DOI: 10.1080/08982104.2019.1634724 -
International Journal of Pharmaceutics Mar 2023Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride...
Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel (PVA@RH@DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.
Topics: Child; Humans; Adolescent; Hydrogels; Osteosarcoma; Doxorubicin; Bone Neoplasms; Cell Line, Tumor
PubMed: 36702387
DOI: 10.1016/j.ijpharm.2023.122637