Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Zhang, Tianyu; Li, Nuannuan; Wang, Ru; Sun, Yiying; He, Xiaoyan; Lu, Xiaoyan; Chu, Liuxiang; Sun, Kaoxiang

doi:10.1080/10717544.2023.2189118

Cited by 10 publications

(3 citation statements)

References 38 publications

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“…Due to the lack of a catalase in heart tissue and a weak antioxidant capacity, DOX.HCl can generate a significant amount of reactive oxygen species (ROS), leading to the indiscriminate movement of these radicals within the body, directly causing DNA strand breakage. Consequently, the mitochondrial DNA of cardiomyocytes is highly susceptible to damage by ROS [8,[60][61][62][63]. Hence, it is crucial to address the issue of eliminating excessive ROS produced by DOX.HCl during tumor cell eradication.…”

Section: Antioxidant Activitymentioning

confidence: 99%

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

Ma,

Li,

Zhang

et al. 2024

Marine Drugs

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The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.

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Section: Antioxidant Activitymentioning

confidence: 99%

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

Ma,

Li,

Zhang

et al. 2024

Marine Drugs

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“…Guo et al [144] reported that EGCG effectively maintains YAP1 within the cytoplasm, enabling assembly of the ESCRT-III complex and ultimately stimulating autophagic apoptosis in BC cells. Alternatively, polyethylene glycol-doxorubicin/EGCG/folic acid inhibits the expression of P-glycoprotein (P-gp) and reverses the multidrug resistance (MDR) of BC cells, thereby enhancing therapeutic efficacy of doxorubicin [145]. Remarkably, paternal consumption of combined botanicals (SFN or EGCG-rich) contribute to the prevention of ER-negative mammary cancer in transgenic mice [123].…”

Section: Egcgmentioning

confidence: 99%

Role of natural products in tumor therapy from basic research and clinical perspectives

Wang,

Liu,

et al. 2024

Acta Materia Medica

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Cancer is the leading cause of morbidity and mortality worldwide and is an important barrier to lengthening life expectancy in every country. Natural products are receiving increased attention from researchers globally and increasing numbers of natural products are approved for clinical studies involving cancer in recent years. To gain more insight into natural products that have undergone clinical trials for cancer treatment, a comprehensive search was conducted. The https://clinicaltrials.gov website was searched for relevant clinical trials and natural product information up to December 2022. The search terms included different types of cancers, such as colorectal, lung, breast, gynecologic, kidney, bladder, melanoma, pancreatic, hepatocellular, gastric and haematologic. Then, PubMed and Web of Science were searched for relevant articles up to February 2024. Hence, we listed existing clinical trials about natural products used in the treatment of cancers and discussed the preclinical and clinical studies of some promising natural products and their targets, indications, and underlying mechanisms of action. Our intent was to provide basic information to readers who are interested or majoring in natural products and obtain a deeper understanding of the progress and actions of natural product mechanisms of action.

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“…However, with the continuous advancement of antitumor drugs, chemotherapy remains the most crucial treatment for TNBC. Anthracycline drugs such as doxorubicin (DOX) are the foundation for breast cancer chemotherapy [ 5 ]. Although studies investigating de-anthracyclines have shown an equal short-term effect in the neoadjuvant stage, the long-term result remains unclear [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide nano-reactor DNMF/PLGA enables tumor vascular microenvironment and chemo-hyperthermia synergetic therapy

Wang,

Cheng,

et al. 2024

J Nanobiotechnol

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Background Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA. Results Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFe2O4), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFe2O4 catalyzes the production of a large amount of reactive oxygen species (ROS) from H2O2, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply H2O2. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFe2O4 served as a chemo-hyperthermia synergistic therapy against TNBC. Conclusion The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC. Graphical Abstract

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Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Cited by 10 publications

References 38 publications

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

Role of natural products in tumor therapy from basic research and clinical perspectives

Nitric oxide nano-reactor DNMF/PLGA enables tumor vascular microenvironment and chemo-hyperthermia synergetic therapy

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