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Advanced Healthcare Materials Dec 2023Nanomedicines are potentially useful for targeted cancer chemotherapy; however, it is difficult to design nanomedicines with controllable structures and functions to...
Nanomedicines are potentially useful for targeted cancer chemotherapy; however, it is difficult to design nanomedicines with controllable structures and functions to overcome a series of biological and pathological barriers to efficiently kill cancer cells in vivo. Here, this work reports in situ growth of dual-acid-sensitive poly(tertiary amine)-doxorubicin conjugates from albumin to form dual-acid-sensitive albumin-poly(tertiary amine)-doxorubicin conjugates that self-assemble into nanospheres and nanoworms in a controlled manner. Both nanospheres and nanoworms rapidly dissociate into positively-charged unimers at pH < 6.9 and quickly releases the conjugated drug of doxorubicin at pH < 5.6, leading to enhanced penetration in tumor cell spheroids as well as improved uptake and cytotoxicity to tumor cells at pH < 6.9. Notably, nanoworms are less taken up by endothelial cells than nanospheres and doxorubicin, leading to improved pharmacokinetics. In a mouse model of triple negative breast cancer, nanoworms accumulate and penetrate into tumors more efficiently than nanospheres and doxorubicin, leading to enhanced tumor accumulation and penetration. As a result, nanoworms outperform nanospheres and doxorubicin in suppressing tumor growth and elongating the animal survival time, without observed side effects. These findings demonstrate that intelligent nanoworms with spatiotemporally programmed dual-acid-sensitive properties are promising as next-generation nanomedicines for targeted cancer chemotherapy.
Topics: Animals; Mice; Endothelial Cells; Doxorubicin; Drug Delivery Systems; Albumins; Amines; Cell Line, Tumor; Neoplasms
PubMed: 37669689
DOI: 10.1002/adhm.202301890 -
Biomedicine & Pharmacotherapy =... Oct 2023A supramolecular redox responsive nanogel (NG) with the ability to sense cancer cells and loaded with a releasing therapeutic agent was synthesized using hostguest...
A supramolecular redox responsive nanogel (NG) with the ability to sense cancer cells and loaded with a releasing therapeutic agent was synthesized using hostguest interactions between polyethylene glycol-grafted-β-cyclodextrin and ferrocene boronic acid. Cyclic voltammetry matched with other spectroscopy and microscopy methods provided strong indications regarding host-guest interactions and formation of the NG. Moreover, the biological properties of the NG were evaluated using fluorescence silencing, confocal laser scanning microscopy, and cell toxicity assays. Nanogel with spherical core-shell architecture and 100-200 nm sized nanoparticles showed high encapsulation efficiency for doxorubicin (DOX) and luminol (LU) as therapeutic and sensing agents. High therapeutic and sensing efficiencies were manifested by complete release of DOX and dramatic quenching of LU fluorescence triggered by 0.05 mM HO (as an ROS component). The NGs showed high ROS sensitivity. Taking advantage of a high loading capacity, redox sensitivity, and biocompatibility, the NGs can be used as strong theranostic systems in inflammation-associated diseases.
Topics: Precision Medicine; Nanogels; Hydrogen Peroxide; Metallocenes; Reactive Oxygen Species; Doxorubicin; Microscopy, Confocal
PubMed: 37660653
DOI: 10.1016/j.biopha.2023.115402 -
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 -
Anticancer Research Nov 2023Previously, selenocompounds (Se-compounds) and in particular selenoesters have shown promising anticancer activities. Since molecular symmetry can enhance the anticancer...
BACKGROUND/AIM
Previously, selenocompounds (Se-compounds) and in particular selenoesters have shown promising anticancer activities. Since molecular symmetry can enhance the anticancer activity, nine symmetrical selenoesters (Se-esters) have been designed as novel, potentially active anticancer agents against doxorubicin resistant breast cancer cells.
MATERIALS AND METHODS
To assess the biological effects of the symmetrical Se-esters, the antiproliferative activity was determined on sensitive MCF-7 and doxorubicin resistant KCR breast cancer cell lines. The interaction of the derivatives with doxorubicin was evaluated by checkerboard combination assay on KCR cells. Furthermore, apoptosis induction and ATPase activity in the presence of Se-esters were also determined on KCR cells.
RESULTS
The symmetrical derivatives showed a noteworthy antiproliferative activity, with two of them showing IC values in submicromolar concentration on MCF-7 cells. In addition, some derivatives showed selectivity towards the resistant KCR cells. The combination of most of them with doxorubicin resulted in synergistic interaction, and all Se-esters could induce early and late apoptosis in KCR cells. Finally, the compounds affected the ATPase activity of ABCB1 (P-gp).
CONCLUSION
The symmetrical Se-esters showed potent anticancer activity, according to in vitro tests. Further research needs to be performed to obtain similar derivatives with a better activity and selectivity, and to ascertain the potential application of these Se-containing compounds using in vivo systems.
Topics: Humans; Female; Breast Neoplasms; Doxorubicin; Apoptosis; Biological Assay; Esters; Adenosine Triphosphatases
PubMed: 37909996
DOI: 10.21873/anticanres.16683 -
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 Healthcare Materials Jun 2024The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic...
The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic constraints due to the unique microenvironment of the tumor itself. Calcium overload, the aberrant accumulation of free calcium ions in the cytoplasm, is a well-recognized contributor to damage and even cell death in numerous cell types. Such undesired destructive processes can be a novel means applicable to cancer ion interference therapy. Herein, the chemotherapeutic drug doxorubicin (DOX) and calcium peroxide as the driving force into nanomotors through a facile and understandable experimental scheme are successfully assembled. The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO/DOX@HPS-IR-1061-AS1411 demonstrates superior killing effects on tumor cells, and the intracellular reactive oxygen species produced by nanomotors is verified by molecular biology experiments to induce apoptosis of tumor cells and further achieve tumor therapeutic effects.
Topics: Doxorubicin; Humans; Animals; Cell Line, Tumor; Mice; Neoplasms; Reactive Oxygen Species; Peroxides; Apoptosis; Aptamers, Nucleotide; Nanoparticles; Antineoplastic Agents; Mice, Nude; Mice, Inbred BALB C
PubMed: 38259234
DOI: 10.1002/adhm.202304212 -
Clinical and Experimental Pharmacology... Nov 2023Preventing or treating heart failure (HF) by blocking cardiomyocyte apoptosis is an effective strategy that improves survival and reduces ventricular remodelling and...
Preventing or treating heart failure (HF) by blocking cardiomyocyte apoptosis is an effective strategy that improves survival and reduces ventricular remodelling and dysfunction in the chronic stage. Autophagy is a mechanism that degrades intracellular components and compensates for energy deficiency, which is commonly observed in cardiomyocytes of failed hearts. Cardiomyocytes activated by doxorubicin (DOX) exhibit strong autophagy. This study aims to investigate the potential protective effect of ligustrazine and its derivative liguzinediol on regulating DOX-induced cardiomyocyte apoptosis and explore the use of the embryonic rat heart-derived myoblast cell line H9C2 for identifying novel treatments for HF. The results indicated that it has been demonstrated to reverse myocardial infarction remodelling in failed hearts by promoting autophagy in salvaged cardiomyocytes and anti-apoptosis of cardiomyocytes in granulation tissue. Our study suggests that ligustrazine and liguzinediol can be a promising agents and autophagy is potential pathway in the management of HF.
Topics: Rats; Animals; Myocytes, Cardiac; Doxorubicin; Heart Failure; Apoptosis; Autophagy
PubMed: 37574718
DOI: 10.1111/1440-1681.13811 -
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 -
Cardiovascular and Interventional... May 2024Antiangiogenic agents have been used for many years as a first-line systemic treatment for advanced HCC. Embolization with cytostatic drugs on the other hand is the...
Combination of Doxorubicin and Antiangiogenic Agents in Drug-Eluting Beads: In Vitro Loading and Release Dynamics in View of a Novel Therapeutic Approach for Hepatocellular Carcinoma.
PURPOSE
Antiangiogenic agents have been used for many years as a first-line systemic treatment for advanced HCC. Embolization with cytostatic drugs on the other hand is the first-line treatment for intermediate HCC. The two types of drugs have not been combined for intraarterial delivery yet. The loading and release dynamics and the in vitro effect of their combination are tested in this experimental study.
MATERIALS AND METHODS
Drug-eluting beads were loaded with doxorubicin, sunitinib and sunitinib analogue piperazine (SAP) alone and with their combinations. Diameter change, loading, release, and effect in cellular proliferation were assessed.
RESULTS
The average microsphere diameter after loading was 473.7 µm (μm) for Doxorubicin, 388.4 μm for Sunitinib, 515.5 μm for SAP, 414.8 μm for the combination Doxorubicin/Sunitinib and 468.8 μm for the combination Doxorubicin /SAP. Drug release in 0.9% NaCl was 10% for Doxorubicin, 49% for Sunitinib, 25% for SAP, 20%/18% for the combination Doxorubicin/Sunitinib, and 18%/23% for the combination Doxorubicin/SAP whereas in human plasma it was 56%, 27%, 13%, 76%/63% and 62%/15%, respectively. The mean concentration of Doxorubicin that led to inhibition of 50% of cellular proliferation in an HCC Huh7 cell line was 163.1 nM (nM), for Sunitinib 10.3 micromolar (μΜ), for SAP 16.7 μΜ, for Doxorubicin/Sunitinib 222.4 nM and for Doxorubicin/SAP 275 nM.
CONCLUSIONS
Doxorubicin may be combined with antiangiogenic drugs with satisfactory in vitro loading and release outcomes and effect on cellular lines.
Topics: Doxorubicin; Carcinoma, Hepatocellular; Sunitinib; Liver Neoplasms; Angiogenesis Inhibitors; Humans; Indoles; Microspheres; Cell Proliferation; Pyrroles; Piperazines; Cell Line, Tumor; Chemoembolization, Therapeutic; In Vitro Techniques; Drug Liberation
PubMed: 38609583
DOI: 10.1007/s00270-024-03714-z -
Pakistan Journal of Biological Sciences... Mar 2024<b>Background and Objective:</b> Doxorubicin is an anticancer therapy belonging to the anthracycline class, which has clinical activity in breast cancer....
<b>Background and Objective:</b> Doxorubicin is an anticancer therapy belonging to the anthracycline class, which has clinical activity in breast cancer. Doxorubicin can cause cardiotoxic effects due to the formation of doxorubicinol as its main metabolite. The purpose of this study was to obtain the optimum sample preparation conditions for the analysis of doxorubicin in VAMS and as a form of therapeutic drug monitoring (TDM) in patients with cancer breasts. <b>Materials and Methods:</b> Analyze doxorubicin and doxorubicinol levels with Volumetric Absorptive Microsampling (VAMS) in patients' cancer breasts receiving doxorubicin in their therapeutic regimen. The sample was analyzed using Ultra Performance Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS). The method uses deep linear range concentrations of 8-200 ng/mL for doxorubicin and 3-100 ng/mL for doxorubicinol. <b>Results:</b> Multiple reaction monitoring (MRM) value set at m/z 544.22>396.9 for doxorubicin; m/z 546.22>398.9 for doxorubicinol and m/z 528.5>362.95 for daunorubicin. The LLOQ value obtained was 8 ng/mL for doxorubicin and 3 ng/mL for doxorubicinol with linearity of 0.9904 for doxorubicin and 0.9902 for doxorubicinol. Analysis results show doxorubicin levels were in the range of 9.47 ng/mL to 87.84 ng/mL and doxorubicinol range between 4.24 and 54.02 ng/mL. <b>Conclusion:</b> Dosage cumulative doxorubicin ranges between 47.93 and 346.09 mg/m<sup>2</sup>; with this, the risk of cardiomyopathy in the patients surveyed is under 4%, according to the literature.
Topics: Doxorubicin; Humans; Breast Neoplasms; Tandem Mass Spectrometry; Female; Cardiotoxicity; Drug Monitoring; Antibiotics, Antineoplastic; Chromatography, Liquid; Chromatography, High Pressure Liquid; Liquid Chromatography-Mass Spectrometry
PubMed: 38686734
DOI: 10.3923/pjbs.2024.125.131