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Einstein (Sao Paulo, Brazil) 2016The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer... (Review)
Review
The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy.
Topics: Antineoplastic Agents; Doxorubicin; Drug Carriers; Humans; Nanoparticles; Neoplasms; Polyethylene Glycols
PubMed: 27074238
DOI: 10.1590/S1679-45082016RB3475 -
Revista Da Associacao Medica Brasileira... Apr 2022We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype...
OBJECTIVE
We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line.
METHODS
Both cell lines were incubated with increasing doses of doxorubicin (1-50 μM) for 24 h at 37°C. Then, half of groups were incubated with 30 μg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry.
RESULTS
Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively).
CONCLUSION
Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Female; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Ozone; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 35649075
DOI: 10.1590/1806-9282.20211193 -
International Journal of Molecular... Jul 2023Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in...
Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in targeted cancer therapies, cytostatic drug combinations remain the gold standard for STS chemotherapy. The lack of algorithms for personalized selection of STS chemotherapy leads to unhelpful treatment of chemoresistant tumors, causing severe side effects in patients. The goal of our study is to assess the applicability of in vitro chemosensitivity/resistance assays (CSRAs) in predicting STS chemoresistance. Primary cell cultures were obtained from 148 surgery samples using enzymatic and mechanical disaggregation. CSRA was performed using resazurin-based metabolic activity measurement in cells cultured with doxorubicin, ifosfamide, their combination and docetaxel, gemcitabine, and also their combination for 7 days. Both the clinical data of patients and the CSRA results demonstrated a higher resistance of some cancer histotypes to specific drugs and their combinations. The correlation between the CSRA results for doxorubicin and ifosfamide and clinical responses to the combination chemotherapy with these drugs was demonstrated via Spearman rank order correlation. Statistically significant differences in recurrence-free survival were also shown for the groups of patients formed, according to the CSRA results. Thus, CSRAs may help both practicing physicians to avoid harmful and useless treatment, and researchers to study new resistance markers and to develop new STS drugs.
Topics: Humans; Ifosfamide; Antineoplastic Combined Chemotherapy Protocols; Sarcoma; Soft Tissue Neoplasms; Doxorubicin
PubMed: 37569668
DOI: 10.3390/ijms241512292 -
Biomaterials Advances Aug 2023Cell-membrane-coated biomimetic nanoparticles (NPs) have attracted great attention due to their prolonged circulation time, immune escape mechanisms and homotypic...
Cell-membrane-coated biomimetic nanoparticles (NPs) have attracted great attention due to their prolonged circulation time, immune escape mechanisms and homotypic targeting properties. Biomimetic nanosystems from different types of cell -membranes (CMs) can perform increasingly complex tasks in dynamic biological environments thanks to specific proteins and other properties inherited from the source cells. Herein, we coated doxorubicin (DOX)-loaded reduction-sensitive chitosan (CS) NPs with 4T1 cancer cell -membranes (CCMs), red blood cell -membranes (RBCMs) and hybrid erythrocyte-cancer membranes (RBC-4T1CMs) to enhance the delivery of DOX to breast cancer cells. The physicochemical properties (size, zeta potential and morphology) of the resulting RBC@DOX/CS-NPs, 4T1@DOX/CS-NPs and RBC-4T1@DOX/CS-NPs, as well as their cytotoxic effect and cellular NP uptake in vitro were thoroughly characterized. The anti-cancer therapeutic efficacy of the NPs was evaluated using the orthotopic 4T1 breast cancer model in vivo. The experimental results showed that DOX/CS-NPs had a DOX-loading capacity of 71.76 ± 0.87 %, and that coating of DOX/CS-NPs with 4T1CM significantly increased the NP uptake and cytotoxic effect in breast cancer cells. Interestingly, by optimizing the ratio of RBCMs:4T1CMs, it was possible to increase the homotypic targeting properties towards breast cancer cells. Moreover, in vivo tumor studies showed that compared to control DOX/CS-NPs and free DOX, both 4T1@DOX/CS-NPs and RBC@DOX/CS-NPs significantly inhibited tumor growth and metastasis. However, the effect of 4T1@DOX/CS-NPs was more prominent. Moreover, CM-coating reduced the uptake of NPs by macrophages and led to rapid clearance from the liver and lungs in vivo, compared to control NPs. Our results suggest that specific self-recognition to source cells resulting in homotypic targeting increased the uptake and the cytotoxic capacity of 4T1@DOX/CS-NPs by breast cancer cells in vitro and in vivo. In conclusion, tumor-disguised CM-coated DOX/CS-NPs exhibited tumor homotypic targeting and anti-cancer properties, and were superior over targeting with RBC-CM or RBC-4T1 hybrid membranes, suggesting that the presence of 4T1-CM is critical for treatment outcome.
Topics: Humans; Female; Breast Neoplasms; Doxorubicin; Antineoplastic Agents; Nanoparticles; Erythrocyte Membrane
PubMed: 37196459
DOI: 10.1016/j.bioadv.2023.213456 -
Journal of Nanobiotechnology Jun 2022Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in...
BACKGROUND
Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in the bone marrow.
RESULTS
Here, a biomimetic nanosystem (DR@PLip) based on platelet membrane (PM) coating and doxorubicin (DOX)/ginsenoside (Rg3) co-loading was developed to potentiate the local-to-systemic chemoimmunotherapy for AML. The PM was designed for long-term circulation and better leukemia cells targeting. The participation of Rg3 was proved to enhance the tumor sensitivity to DOX, thus initiating the anti-tumor immune activation and effectively combating the leukemia cells hiding in the bone marrow.
CONCLUSIONS
In conclusion, the strategy that combining immediate chemotherapy with long-term immunotherapy achieved improved therapeutic efficiency and prolonged survival, which provided a new perspective for the clinical treatment of AML.
Topics: Biomimetics; Doxorubicin; Ginsenosides; Humans; Immunotherapy; Leukemia, Myeloid, Acute
PubMed: 35701846
DOI: 10.1186/s12951-022-01491-w -
Blood Advances Jan 2024Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival...
Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective noninterventional multicentric cohort started in 2018 that included patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on patients with first-line diffuse large B-cell lymphoma (DLBCL) to (1) evaluate the capacity of the cohort to provide robust data through a multistep validation process; (2) assess the consistency of the results; and (3) conduct an exploratory transportability assessment of 2 recent phase 3 CTs (POLARIX and SENIOR). The analysis population comprised 645 patients with DLBCL included before 31 March 2021 who received immunochemotherapy and for whom 3589 queries were generated, resulting in high data completeness (<4% missing data). Median age was 66 years, with mostly advanced-stage disease and high international prognostic index (IPI) score. Treatments were mostly rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP 75%) and reduced dose R-CHOP (13%). Estimated 1-year event-free survival (EFS) and overall survival rates were 77.9% and 90.0%, respectively (median follow-up, 9.9 months). Regarding transportability, when applying the CT's main inclusion criteria (age, performance status, and IPI), outcomes seemed comparable between patients in REALYSA and standard arms of POLARIX (1-year progression-free survival 79.8% vs 79.8%) and SENIOR (1-year EFS, 64.5% vs 60.0%). With its rigorous data validation process, REALYSA provides high-quality RWD, thus constituting a platform for numerous scientific purposes. The REALYSA study was registered at www.clinicaltrials.gov as #NCT03869619.
Topics: Adult; Humans; Aged; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Rituximab; Lymphoma, Large B-Cell, Diffuse; Cyclophosphamide; Prednisone; Vincristine; Doxorubicin
PubMed: 37874913
DOI: 10.1182/bloodadvances.2023010798 -
Cell Proliferation May 2023Cancer cell spheroids have been shown to mimic in vivo tumour microenvironment and are therefore suitable for in vitro drug screening. Microfluidic technology can...
Cancer cell spheroids have been shown to mimic in vivo tumour microenvironment and are therefore suitable for in vitro drug screening. Microfluidic technology can provide conveniences for spheroid assays such as high-throughput, simplifying manual operation and saving reagent. Here, we propose a concentration gradient generator based on microfluidic technology for cell spheroid culture and assay. The chip consists of upper microchannels and lower microwells. After partitioning HepG2 suspension into the microwells with concave and non-adhesive bottoms, spheroids can spontaneously form. By controlling the fluid replacement and flow in microchannels, the doxorubicin solution is diluted automatically into a series of concentration gradients, which spanning more than one order of magnitude. And then the effect of doxorubicin on spheroids is measured in situ by fluorescent staining. This chip provides a very promising approach to achieve the high-throughput and standardized anti-cancer drug screening in future.
Topics: Spheroids, Cellular; Cell Culture Techniques; Antineoplastic Agents; Drug Evaluation, Preclinical; Doxorubicin
PubMed: 37199072
DOI: 10.1111/cpr.13473 -
Biochimica Et Biophysica Acta.... Aug 2017Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to...
Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potential mechanisms of protective effects of rutin against cardiomyocyte death. We analyzed cardiac tissues at the time point of 8weeks after doxorubicin treatment. The results by echocardiography, TUNEL staining, Masson's trichrome staining as well as Western blot analysis revealed that doxorubicin induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were alleviated by rutin treatment. Western blot analysis indicated that the underlying mechanisms included inhibition excessive autophagy and apoptosis mediated by Akt activation. Collectively, our findings suggest that suppression of autophagy and apoptosis by administration of rutin could attenuate doxorubicin-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating this devastating side effect induced by doxorubicin. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.
Topics: Animals; Apoptosis; Autophagy; Cardiotoxins; Doxorubicin; Male; Mice; Rutin
PubMed: 28069395
DOI: 10.1016/j.bbadis.2016.12.021 -
International Journal of Nanomedicine 2022Osteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far...
PURPOSE
Osteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far from satisfactory. Localized tumor treatments by hydrogels incorporating combined chemotherapeutic drugs have recently emerged as superior approaches for enhanced anti-tumor effects and reduced systemic toxicity.
METHODS
A novel injectable thermosensitive poly (lactide-co- glycolide)-poly (ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer hydrogel containing doxorubicin and cisplatin for the localized chemotherapy of osteosarcoma were synthesized and characterized. The in vitro drug release properties of the drugs-loaded hydrogels were investigated. To study the anti-tumor efficacy of hydrogels depots in vitro, the cytotoxicity and apoptosis rate against Saos-2 and MG-63 cells were evaluated by MTT, Annexin V and PCR methods. The in vivo synergistic anti-tumor efficacy of the multi-drugs co-loaded hydrogels was investigated by human osteosarcoma xenografts. Additionally, the systemic toxic side effects were evaluated by ex vivo histological analysis of the major organs of the mice.
RESULTS
The PLGA-PEG-PLGA copolymer solution underwent a sol-gel transition at appropriate temperature and degraded in the PBS, presenting a friendly biocompatibility in vitro. The in vitro cell viability tests demonstrated that DOX and CDDP co-loaded hydrogels exhibited synergistic anti-proliferation effect, due to the sustained release of drugs from the drugs-loaded hydrogel. The treatment with DOX and CDDP co-loaded hydrogel led to the highest efficiency in inhibiting the tumor growth, enhanced tumor necrosis rate and increased regulation of the apoptosis-related gene expressions, indicating a synergistic anti-tumor efficacy in vivo. Additionally, ex vivo histological analysis of the nude mice exhibited low systemic toxicity.
CONCLUSION
The combination treatment of osteosarcoma by localized, sustained co-delivery of DOX and CDDP by PLGA-PEG-PLGA hydrogel may serve as a promising strategy for efficient clinical treatment of osteosarcoma.
Topics: Adolescent; Animals; Bone Neoplasms; Cisplatin; Doxorubicin; Humans; Hydrogels; Mice; Mice, Nude; Osteosarcoma
PubMed: 35345787
DOI: 10.2147/IJN.S356453 -
International Journal of Pharmaceutics May 2017Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we...
Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we show how the analysis of sedimentation velocity data from the AUC can be used to characterize nanocarrier drug delivery systems used in nanomedicine. Nanocarrier size distribution and the ratio of free versus nanoparticle-encapsulated drug in a commercially available liposomal doxorubicin formulation are determined using interference and absorbance based AUC measurements and compared with results generated with conventional techniques. Additionally, the potential of AUC in measuring particle density and the detection of nanocarrier sub-populations is discussed as well. The unique capability of AUC in providing reliable data for size and composition in a single measurement and without complex sample preparation makes this characterization technique a promising tool both in nanomedicine product development and quality control.
Topics: Antibiotics, Antineoplastic; Doxorubicin; Nanomedicine; Particle Size; Polyethylene Glycols; Ultracentrifugation
PubMed: 28342788
DOI: 10.1016/j.ijpharm.2017.03.046