A novel doxorubicin/CTLA-4 blocker co-loaded drug delivery system improves efficacy and safety in antitumor therapy

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 1, 2024

Abstract Doxorubicin’s antitumor effectiveness may be constrained with ineffective tumor penetration, systemic adverse effects, as well drug resistance. The co-loading of immune checkpoint inhibitors and doxorubicin into liposomes can produce synergistic benefits address problems, including quick clearance, toxicity, low penetration efficiency. In our previous study, we modified a nanobody targeting CTLA-4 onto (LPS-Nb36) to an extremely potent signal blocker which improve the CD8 + T-cell activity against tumors under physiological conditions. this designed delivery system (LPS-RGD-Nb36-DOX) based on LPS-Nb36 that realized anti-CTLA-4 Nb co-loaded RGD modification, was applied therapy. We tested whether LPS-RGD-Nb36-DOX could targets by in vivo animal photography, more importantly, promote cytotoxic T cells proliferation, pro-inflammatory cytokine production, cytotoxicity. Our findings demonstrated combination activated doxorubicin/anti-CTLA-4 effectively eradicate both vitro. This therapy is anticipated have effects. More it has potential reduce dose chemotherapeutic drugs safety.

Language: Английский

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Potential of Natural Phenolic Compounds against Doxorubicin-Induced Chemobrain: Biological and Molecular Mechanisms Involved

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 486 - 486

Published: April 18, 2024

Chemotherapy-induced cognitive impairment or "chemobrain" is a prevalent long-term complication of chemotherapy and one the more devastating. Most studies performed so far to identify dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered breast cancer patients, population that, after treatment, shows high possibility long survival and, consequently, chemobrain development. In last few years, different possible strategies explored prevent reduce anthracycline doxorubicin (DOX), known promote oxidative stress inflammation, which strongly implicated in development this brain dysfunction. Here, we critically analyzed results preclinical from years that evaluated potential phenolic compounds (PheCs), large class natural products able exert powerful antioxidant anti-inflammatory activities, inhibiting DOX-induced chemobrain. Several PheCs belonging classes shown be revert morphological damages deficits associated learning, memory, exploratory behavior. We biological molecular mechanisms suggested future perspectives research area.

Language: Английский

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Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

AMB Express, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 24, 2024

Abstract Doxorubicin is an important class of anthracycline antitumor antibiotics produced by Streptomyces peucetius . The doxorubicin fermentation yield the wild-type strain was very low, so it could not be directly at industrial scale due to high cost. In present study, S. SIPI-7-14 obtained from SIPI-14 through several rounds resistance screening. Then, ketoreductase gene dnrU knocked out reduce (13 S )-13-dihydrodaunorubicin production, and drrC overexpressed further enhance doxorubicin. resulting engineered △U1/ 1128 mg/L doxorubicin, a 102.1% increase compared that SIPI-14. medium optimized using response surface method. medium, increased 1406 in shake flask on 7th day. Furthermore, batch culture carried 10 L fermenter, concentration reached 1461 after 7 days culture, which highest reported date, indicating potential for production fermentation.

Language: Английский

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Emerging role of MYB transcription factors in cancer drug resistance

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Decades ago, the viral myeloblastosis oncogene v -myb was identified as a gene responsible for development of avian leukemia. However, relevance MYB proteins human cancer diseases, in particular solid tumors, remained basically unrecognized very long time. The family transcription factors comprises (c-MYB), MYBL2 (b-MYB), and MYBL1 (a-MYB), which are overexpressed several cancers associated with progression resistance to anticancer drugs. In addition overexpression, presence activated MYB-fusion tumor drivers described certain cancers. identification drug mediated by their underlying mechanisms great importance understanding failures current therapies establishing new more efficient therapy regimens. addition, candidates targeting factor activity signaling have emerged promising class potential therapeutics that could tackle MYB-dependent drug-resistant selective way. This review describes correlation formation persistence various approved investigational

Language: Английский

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Mechanistic study of Huangqi Guizhi Wuwu decoction amelioration of doxorubicin-induced cardiotoxicity by reducing oxidative stress and inhibiting cellular pyroptosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116653 - 116653

Published: April 30, 2024

Huangqi Guizhi Wuwu Decoction (HQGZWWD) has shown promising potential in treating various cardiovascular diseases. This study aimed to elucidate the molecular basis and therapeutic role of HQGZWWD treatment doxorubicin (DOX)-induced myocardial injury. The HPLC fingerprint was used analyze active components. A DOX-induced damage rat model developed, effects were evaluated using echocardiography, enzyme levels, hematoxylin eosin staining. Network pharmacology screen targets, western blotting immunohistochemistry performed assess cellular pyroptosis levels. Oxidative stress levels measured assay kits, mitochondrial examined transmission electron microscopy. An vitro cell established, administered serum containing N-acetylcysteine (NAC). detected kits DCFH-DA, whereas assessed through WB, immunofluorescence, ELISA assays. ameliorated identified IL-1β IL-18 as crucial targets. downregulated protein inflammatory factors IL-18, inhibited expression GSDMD-NT, simultaneously suppressed synthesis Caspase-1, ASC, NLRP3, Caspase-11. Additionally, oxidative stress, use NAC an inhibitor resulted significant inhibition GSDMD-NT H9C2 cells. These findings highlight protective by inhibiting suppressing both canonical non-canonical pyroptotic pathways.

Language: Английский

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Mass Production of Rg1-Loaded Small Extracellular Vesicles Using a 3D Bioreactor System for Enhanced Cardioprotective Efficacy of Doxorubicin-Induced Cardiotoxicity

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(5), P. 593 - 593

Published: April 26, 2024

Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, were developed deliver Ginsenoside Rg1 (Rg1), compound derived traditional Chinese medicine, Ginseng, that has properties but bioavailability, enhance treatment DIC. Methods: The 3D system with spinner flasks was used expand MSCs collect MSC-conditioned medium. Subsequently, isolated conditioned medium differential ultra-centrifugation (dUC). loaded by electroporation evaluated for Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining live cell count H9c2 under Results: Using flasks, expansion reached ~600 million, up 2.2 × 1012 particles five days significantly reduced bench work compared 2D flasks. With optimized protocol, loading efficiency ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded had attenuated DOX-induced apoptosis free sEVs. Conclusions: culture scaled sEVs, which facilitated delivery cardiomyocyte apoptosis, suggesting potential cardiotoxicity.

Language: Английский

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Baicalin and Baicalein Enhance Cytotoxicity, Proapoptotic Activity, and Genotoxicity of Doxorubicin and Docetaxel in MCF-7 Breast Cancer Cells

Molecules, Journal Year: 2024, Volume and Issue: 29(11), P. 2503 - 2503

Published: May 25, 2024

Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, chemotherapy, but these come with side effects limitations. Researchers are exploring natural compounds like baicalin baicalein, derived from Scutellaria baicalensis plant, as potential complementary therapies. This study investigated baicalein on cytotoxic, proapoptotic, genotoxic activity doxorubicin docetaxel, commonly used chemotherapeutic drugs for breast cancer. The analysis included cells (MCF-7) human endothelial (HUVEC-ST), to assess healthy tissues. We have found that demonstrated cytotoxicity towards both cell lines, more potent observed in baicalein. Both flavonoids, (167 µmol/L) (95 µmol/L), synergistically enhanced docetaxel cells. In comparison, their were mixed depended concentration time. results suggest might be promising agents improve efficacy anticancer activity. However, further research needed validate safety clinical trials.

Language: Английский

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Chemoradiotherapy and nanomedicine: Drug mechanisms and delivery systems

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2024, Volume and Issue: 16(4)

Published: July 1, 2024

Abstract Radiotherapy is an invaluable tool in the treatment of cancer. However, when used as a monotherapy, it fails to provide curative outcomes. Chemotherapy drugs are often included boost effects radiation. Key classes radiosensitizing include platinum compounds, anthracyclines, antimetabolites, taxanes, topoisomerase inhibitors, alkylating agents, and DNA damage repair inhibitors. Chemoradiotherapy suffers from not only systemic toxicities chemotherapy but also synergistic radiation toxicity well. It critical deliver molecules tumor cells while avoiding adjacent healthy tissues. Currently, nanomedicine provides avenue for specific delivery radiosensitizers. Nanoscale vehicles can be synthesized lipids, polymers, or inorganic materials. Additionally, encompasses stimuli responsive particles including prodrug formulation activation. Clinically, radiotherapy intertwined with approved DOXIL Abraxane. Though many challenges remain, ongoing progress evidences promising future both chemoradiotherapy. This article categorized under: Therapeutic Approaches Drug Discovery > Nanomedicine Oncologic Disease Cardiovascular Emerging Technologies

Language: Английский

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Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity

Cardiovascular Toxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Language: Английский

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Role of Folate Receptor and CD44 in Targeting of Docetaxel and Paclitaxel Fabricated Conjugates for Efficient Cancer Therapy

Journal of Medicine Surgery and Public Health, Journal Year: 2024, Volume and Issue: unknown, P. 100163 - 100163

Published: Dec. 1, 2024

Language: Английский

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