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JACC. Clinical Electrophysiology Aug 2023The authors sought to evaluate a method for improving radiofrequency (RF) lesion durability using doxorubicin encased in heat-sensitive liposomes (HSL-dox). Using a... (Review)
Review
The authors sought to evaluate a method for improving radiofrequency (RF) lesion durability using doxorubicin encased in heat-sensitive liposomes (HSL-dox). Using a porcine model, RF ablations were performed in the right atrium after systemic infusion of either HSL-dox or saline control given immediately before mapping and ablation. Lesion geometry was measured with voltage mapping immediately postablation and after 2 weeks of survival. After 2 weeks, lesions demonstrated less regression in scar area in HSL-dox-exposed animals compared with control animals. We demonstrate improved RF lesion durability in animals treated with HSL-dox, and the cardiotoxic effect was more pronounced after RF applications with higher power and longer duration.
Topics: Swine; Animals; Liposomes; Hot Temperature; Myocardium; Doxorubicin; Heart Atria
PubMed: 37227346
DOI: 10.1016/j.jacep.2023.02.025 -
International Journal of Pharmaceutics May 2024Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX...
Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and -5.80 mV - -18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment.
Topics: Doxorubicin; Humans; Drug Carriers; Nanoparticles; Lipids; Cell Line, Tumor; Particle Size; Drug Liberation; Cell Survival; Antibiotics, Antineoplastic; Nanostructures; Drug Stability; HeLa Cells; A549 Cells; Antineoplastic Agents
PubMed: 38537925
DOI: 10.1016/j.ijpharm.2024.124048 -
ACS Applied Materials & Interfaces Jul 2023Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a...
Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a pressing endeavor. Here, we report a multifunctional framework nucleic acid (FNA) nanosystem for simultaneous imaging of microRNA-21 (miR-21) and combined chemo/gene therapy. To achieve this, two FNA nanoarchitectures labeled with Cy5/BHQ2 signal tags were designed, each of which contained an AS1411 aptamer, two pairs of DNA/RNA hybrids, a pH-sensitive DNA catcher, and doxorubicin (DOX) intercalating between cytosine and guanine in the tetrahedral DNA nanostructure (TDN). In the acidic tumor microenvironment, the DNA catchers spontaneously triggered to form an i-motif and create an FNA dimer (dFNA) while releasing DOX molecules to exert a cytotoxic effect. In addition, the overexpressed miR-21 in tumor cells dismantled the DNA/RNA hybrids to produce vascular endothelial growth factor-associated siRNA via a toehold-mediated strand displacement reaction, thus enabling a potent RNA interfering. Also importantly, the liberated miR-21 could initiate cascade-reaction amplification to efficiently activate the Cy5 signal reporters, thereby realizing on-site fluorescence imaging of miR-21 in living cells. The exquisitely designed FNA-based nanosystem showed favorable biocompatibility and stability as well as acid-driven DOX release characteristics. Owing to the aptamer-guided targeting delivery, specific uptake of the FNA-based theranostic nanosystem by HepG2 cells was verified with confocal laser scanning microscopy and flow cytometry analyses, which therefore resulted in apoptosis of HepG2 cells while doing minimal damage to normal H9c2 and HL-7702 cells. Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.
Topics: Humans; MicroRNAs; Nucleic Acids; Precision Medicine; Vascular Endothelial Growth Factor A; Neoplasms; Doxorubicin; DNA; Optical Imaging; RNA, Small Interfering; Theranostic Nanomedicine; Cell Line, Tumor; Nanoparticles; Tumor Microenvironment
PubMed: 37421332
DOI: 10.1021/acsami.3c01611 -
Cardiovascular Toxicology Aug 2023Doxorubicin is associated with cardiotoxicity, and physical exercise seeks to minimize the toxic effects of doxorubicin through physiological cardiac remodeling, as well...
Doxorubicin is associated with cardiotoxicity, and physical exercise seeks to minimize the toxic effects of doxorubicin through physiological cardiac remodeling, as well as the reduction of oxidative stress, evidenced by previous studies. This study aimed to analyze whether running training before treatment with doxorubicin influences tolerance to physical exertion and cardiotoxicity. Thirty-nine male Wistar rats, aged 90 days and weighing between 250 and 300 g, were divided into 4 groups: Control (C), Doxorubicin (D), Trained (T), and Trained + Doxorubicin (TD). Animals in groups T and DT were submitted to treadmill running for 3 weeks, 5 times a week at 18 m/min for 20-30 min before treatment with doxorubicin. Animals in groups D and DT received intraperitoneal injections of doxorubicin hydrochloride three times a week for two weeks, reaching a total cumulative dose of 7.50 mg/kg. Our results show an increase in total collagen fibers in the D group (p = 0.01), but no increase in the TD group, in addition to the attenuation of the number of cardiac mast cells in the animals in the TD group (p = 0.05). The animals in the TD group showed maintenance of tolerance to exertion compared to group D. Therefore, running training attenuated the cardiac damage caused by the treatment with doxorubicin, in addition to maintaining the tolerance to exertion in the rats.
Topics: Rats; Male; Animals; Cardiotoxicity; Antibiotics, Antineoplastic; Rats, Wistar; Physical Conditioning, Animal; Doxorubicin
PubMed: 37402033
DOI: 10.1007/s12012-023-09798-2 -
Small (Weinheim An Der Bergstrasse,... Nov 2023Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for...
Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for on-demand multidrug delivery. By combining magnetic targeting transportation with tumor therapy, it is hypothesized that loading multiple drugs on different regions of a single magnetic microrobot can enhance a synergistic effect for cancer treatment. The synergistic effect of using two drugs together is greater than that of using each drug separately. Here, a 3D-printed microrobot inspired by the fish structure with three hydrogel components: skeleton, head, and body structures is demonstrated. Made of iron oxide (Fe O ) nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA), the skeleton can respond to magnetic fields for microrobot actuation and drug-targeted delivery. The drug storage structures, head, and body, made by biodegradable gelatin methacryloyl (GelMA) exhibit enzyme-responsive cargo release. The multidrug delivery microrobots carrying acetylsalicylic acid (ASA) and doxorubicin (DOX) in drug storage structures, respectively, exhibit the excellent synergistic effects of ASA and DOX by accelerating HeLa cell apoptosis and inhibiting HeLa cell metastasis. In vivo studies indicate that the microrobots improve the efficiency of tumor inhibition and induce a response to anti-angiogenesis. The versatile multidrug delivery microrobot conceptualized here provides a way for developing effective combination therapy for cancer.
Topics: Humans; Animals; HeLa Cells; Drug Delivery Systems; Polyethylene Glycols; Hydrogels; Doxorubicin; Neoplasms
PubMed: 37423966
DOI: 10.1002/smll.202301889 -
Journal of Chemotherapy (Florence,... Apr 2024Chemotherapy resistance is the major cause of treatment failure in osteosarcoma, the most common primary bone malignancy, and sensitizing therapeutic strategy is...
Chemotherapy resistance is the major cause of treatment failure in osteosarcoma, the most common primary bone malignancy, and sensitizing therapeutic strategy is required to improve the clinical outcome. In this study, we discovered that navitoclax, a selective inhibitor of Bcl-2/Bcl-xL, effectively combats chemoresistance in osteosarcoma. Our research revealed that Bcl-2, but not Bcl-xL, is upregulated in osteosarcoma cells that are resistant to doxorubicin. However, venetoclax, a specific inhibitor of Bcl-2, did not exhibit activity against doxorubicin-resistant cells. Further analysis showed that depleting either Bcl-2 or Bcl-xL alone was insufficient to overcome doxorubicin resistance. Only by depleting both Bcl-2 and Bcl-xL significantly reduce the viability of doxorubicin-resistant cells. Similarly, navitoclax not only decreased the viability of doxorubicin-resistant cells but also acted synergistically with doxorubicin in cells sensitive to the drug. To confirm the ability of navitoclax to overcome doxorubicin resistance, we conducted experiments using multiple mouse models of osteosarcoma, both doxorubicin-sensitive and doxorubicin-resistant. The results provided confirmation that navitoclax is effective in overcoming doxorubicin resistance. Our findings demonstrate that simultaneous inhibition of Bcl-2 and Bcl-xL could serve as a novel strategy to sensitize chemoresistant osteosarcoma cells. Moreover, our study presents preclinical evidence supporting the potential of a navitoclax and doxorubicin combination therapy for the treatment of osteosarcoma, paving the way for future clinical investigations.
Topics: Animals; Mice; bcl-X Protein; Apoptosis; Cell Line, Tumor; Proto-Oncogene Proteins c-bcl-2; Doxorubicin; Osteosarcoma; Bone Neoplasms; Drug Resistance, Neoplasm; Aniline Compounds; Sulfonamides
PubMed: 37309095
DOI: 10.1080/1120009X.2023.2220583 -
Advanced Materials (Deerfield Beach,... May 2024Intravesical Bacillus Calmette-Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of...
Intravesical Bacillus Calmette-Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the "biotin-streptavidin strategy" to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.
Topics: Urinary Bladder Neoplasms; Animals; Doxorubicin; Immunotherapy; Mice; Humans; Nanoparticles; Cell Line, Tumor; Mycobacterium bovis; Rats; BCG Vaccine; Antineoplastic Agents; Streptavidin
PubMed: 38330363
DOI: 10.1002/adma.202310735 -
Scientific Reports Feb 2024Breast cancer therapy options are limited due to its late diagnosis and poor prognosis. Doxorubicin is the fundamental therapy approach for this disease. Because...
Breast cancer therapy options are limited due to its late diagnosis and poor prognosis. Doxorubicin is the fundamental therapy approach for this disease. Because chemotherapy has numerous adverse effects, the scope of the existing research was to appraise the synergetic effect of doxorubicin and naringin and explore the underlying mechanism. The cytotoxicity of doxorubicin and naringin on MCF-7 was monitored. Furthermore, the expression of STAT3 and JAK1 as well as the apoptotic and metastatic related genes (Bax, Bcl-2, Survivin, and VEGF) were conducted by immunoblotting assay and qRT-PCR. In addition, a wound healing test was utilized to appraise the migration and metastasis of MCF-7. Our results revealed that naringin and doxorubicin had a synergetic inhibitory influence on MCF-7 cells growth and migration. The synergetic action of doxorubicin and naringin effectively hindered the expression of STAT3, JAK1, Bcl-2, Survivin, and VEGF, with a boost in the level of Bax compared to cells treated with either doxorubicin or naringin. In conclusion, our findings imply that combining doxorubicin with naringin may be a favorable strategy for inhibiting the growth of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Survivin; bcl-2-Associated X Protein; Vascular Endothelial Growth Factor A; Apoptosis; Doxorubicin; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Cell Line, Tumor; Flavanones
PubMed: 38310190
DOI: 10.1038/s41598-024-53320-9 -
Respiratory Research Jan 2024Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest,...
Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicin-induced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing.
Topics: Animals; Quercetin; Cellular Senescence; Lung; Cystic Fibrosis; Gene Expression Profiling; Doxorubicin; Organoids
PubMed: 38172839
DOI: 10.1186/s12931-023-02636-7 -
In Vivo (Athens, Greece) 2024Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma...
BACKGROUND/AIM
Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice.
PATIENTS AND METHODS
Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated.
RESULTS
The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death.
CONCLUSION
The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.
Topics: Humans; Female; Male; Aged; Doxorubicin; Middle Aged; Sarcoma; Retroperitoneal Neoplasms; Treatment Outcome; Aged, 80 and over; Neoplasm Metastasis; Adult; Retrospective Studies; Neoplasm Staging
PubMed: 38936944
DOI: 10.21873/invivo.13640