ArticleMolecular pharmaceutics2020
Chemical Architecture of Block Copolymers Differentially Abrogate Cardiotoxicity and Maintain the Anticancer Efficacy of Doxorubicin.
Article in Molecular pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 46 citations in OpenAlex.
- Long-Term Effectiveness of a Decision Support App (Pink Journey) for Women Considering Breast Reconstruction Surgery: Pilot Randomized Controlled Trial.JMIR mHealth and uHealth · 2021Trial
- A recent decade update on combating doxorubicin-induced toxicities.Archives of toxicology · 2025Review
- Enhanced FGF21 Delivery via Neutrophil-Membrane-Coated Nanoparticles Improves Therapeutic Efficacy for Myocardial Ischemia-Reperfusion Injury.Nanomaterials (Basel, Switzerland) · 2025Article
- Tumor hypoxia unveiled: insights into microenvironment, detection tools and emerging therapies.Clinical and experimental medicine · 2024Review
- Article
- Article
- Preparation of Doxorubicin-Loaded Carboxymethyl-β-Cyclodextrin/Chitosan Nanoparticles with Antioxidant, Antitumor Activities and pH-Sensitive Release.Marine drugs · 2022Article
- Bio-Responsive Carriers for Controlled Delivery of Doxorubicin to Cancer Cells.Pharmaceutics · 2022Article
- Monitoring Mitochondrial Morphology and Respiration in Doxorubicin-Induced Cardiomyopathy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Description of Release Process of Doxorubicin from Modified Carbon Nanotubes.International journal of molecular sciences · 2021Article
- New side chain design for pH-responsive block copolymers for drug delivery.Colloids and surfaces. B, Biointerfaces · 2021Article
- Cell-morphodynamic phenotype classification with application to cancer metastasis using cell magnetorotation and machine-learning.PloS one · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The molecular architecture of pH-responsive amphiphilic block copolymers, their self-assembly behavior to form nanoparticles (NPs), and doxorubicin (DOX)-loading technique govern the extent of DOX-induced cardiotoxicity. We observed that the choice of pH-sensitive tertiary amines, surface charge, and DOX-loading techniques within the self-assembled NPs strongly influence the release and stimulation of DOX-induced cardiotoxicity in primary cardiomyocytes. However, covalent conjugation of DOX to a pH-sensitive nanocarrier through a "conditionally unstable amide" linkage (PCPY-cDOX; PC = polycarbonate and PY = 2-pyrrolidine-1-yl-ethyl-amine) significantly reduced the cardiotoxicity of DOX in cardiomyocytes as compared to noncovalently encapsulated DOX NPs (PCPY-eDOX). When these formulations were tested for drug release in serum-containing media, the PCPY-cDOX systems showed prolonged control over drug release (for ∼72 h) at acidic pH compared to DOX-encapsulated nanocarriers, as expected. We found that DOX-encapsulated nanoformulations triggered cardiotoxicity in primary cardiomyocytes more acutely, while conjugated systems such as PCPY-cDOX prevented cardiotoxicity by disabling the nuclear entry of the drug. Using 2D and 3D (spheroid) cultures of an ER + breast cancer cell line (MCF-7) and a triple-negative breast cancer cell line (MDA-MB-231), we unravel that, similar to encapsulated systems (PCPY-eDOX-type) as reported earlier, the PCPY-cDOX system suppresses cellular proliferation in both cell lines and enhances trafficking through 3D spheroids of MDA-MB-231 cells. Collectively, our studies indicate that PCPY-cDOX is less cardiotoxic as compared to noncovalently encapsulated variants without compromising the chemotherapeutic properties of the drug. Thus, our studies suggest that the appropriate selection of the nanocarrier for DOX delivery may prove fruitful in shifting the balance between low cardiotoxicity and triggering the chemotherapeutic potency of DOX.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.