Differential Cytotoxicity of PVP-Copper Nanoparticles in Breast Cancer Cell Lines: Insights from Basal Transcriptomic Profiles
- 1University of Campinas
Abstract
Breast cancer is a heterogeneous disease comprising molecular subtypes with distinct therapeutic vulnerabilities. Among emerging therapeutic strategies, copper-based nanoparticles have shown anticancer activity. However, whether these responses differ across breast cancer subtypes and which molecular programs underlie copper sensitivity remain poorly understood. We investigated subtype-specific responses to Polyvinylpyrrolidone-assisted copper nanoparticles (CuNP-PVP) in breast cancer cell lines and the molecular programs underlying copper adaptation. CuNP-PVP were synthesized and evaluated in luminal (MCF-7), HER2-positive (SKBR3), and triple-negative (MDA-MB-231) breast cancer cell lines, with transcriptomic analyses integrated with CCLE and TCGA-BRCA datasets. UV-Vis spectroscopy revealed a plasmon resonance band at 591 nm, while TEM showed spherical nanoparticles with an average diameter of 76.1 +/- 21.0 nm. DLS indicated a larger hydrodynamic diameter, consistent with PVP coating; {zeta}-potential measurements showed a surface charge of -13 mV, and XPS confirmed mixed reduced and Cu(I)/Cu(II) oxidation states. Exposure to 100 g/mL CuNP-PVP induced subtype-dependent effects on cell viability, with MCF-7 showing greater sensitivity, whereas MDA-MB-231 and SKBR3 were less affected. Baseline transcriptomic analyses revealed enrichment of oxidative stress, metabolic adaptation, and lysosomal programs in less sensitive cells, whereas MCF-7 showed higher expression of lipoylation-related genes. These features supported the development of a Potential Biological Copper-Response Index (PBCRI), which captured subtype-associated transcriptional patterns across independent cell lines and patient tumors, with luminal models showing lower scores and basal/TNBC models showing higher scores. Together, these findings identify candidate transcriptional programs associated with subtype-specific responses to CuNP and provide a framework for investigating potential molecular determinants of copper sensitivity.
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BibTeX
@misc{silva2026differential,
title = {{Differential Cytotoxicity of PVP-Copper Nanoparticles in Breast Cancer Cell Lines: Insights from Basal Transcriptomic Profiles}},
author = {A. Goncalves Silva and I. J. Oliveira Silva and P. Paranhos Tanaka and M. Zaia Monteiro and S. Servilha Oliveira Filho and J. F. Moreira de Oliveira and V. Spolon Marangoni and S. M. Gomes Dias and C. von Zuben de Valega Negrao},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753010},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753010v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Differential Cytotoxicity of PVP-Copper Nanoparticles in Breast Cancer Cell Lines: Insights from Basal Transcriptomic Profiles
AU - A. Goncalves Silva
AU - I. J. Oliveira Silva
AU - P. Paranhos Tanaka
AU - M. Zaia Monteiro
AU - S. Servilha Oliveira Filho
AU - J. F. Moreira de Oliveira
AU - V. Spolon Marangoni
AU - S. M. Gomes Dias
AU - C. von Zuben de Valega Negrao
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753010
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753010v1
AB - Breast cancer is a heterogeneous disease comprising molecular subtypes with distinct therapeutic vulnerabilities. Among emerging therapeutic strategies, copper-based nanoparticles have shown anticancer activity. However, whether these responses differ across breast cancer subtypes and which molecular programs underlie copper sensitivity remain poorly understood. We investigated subtype-specific responses to Polyvinylpyrrolidone-assisted copper nanoparticles (CuNP-PVP) in breast cancer cell lines and the molecular programs underlying copper adaptation. CuNP-PVP were synthesized and evaluated in luminal (MCF-7), HER2-positive (SKBR3), and triple-negative (MDA-MB-231) breast cancer cell lines, with transcriptomic analyses integrated with CCLE and TCGA-BRCA datasets. UV-Vis spectroscopy revealed a plasmon resonance band at 591 nm, while TEM showed spherical nanoparticles with an average diameter of 76.1 +/- 21.0 nm. DLS indicated a larger hydrodynamic diameter, consistent with PVP coating; {zeta}-potential measurements showed a surface charge of -13 mV, and XPS confirmed mixed reduced and Cu(I)/Cu(II) oxidation states. Exposure to 100 g/mL CuNP-PVP induced subtype-dependent effects on cell viability, with MCF-7 showing greater sensitivity, whereas MDA-MB-231 and SKBR3 were less affected. Baseline transcriptomic analyses revealed enrichment of oxidative stress, metabolic adaptation, and lysosomal programs in less sensitive cells, whereas MCF-7 showed higher expression of lipoylation-related genes. These features supported the development of a Potential Biological Copper-Response Index (PBCRI), which captured subtype-associated transcriptional patterns across independent cell lines and patient tumors, with luminal models showing lower scores and basal/TNBC models showing higher scores. Together, these findings identify candidate transcriptional programs associated with subtype-specific responses to CuNP and provide a framework for investigating potential molecular determinants of copper sensitivity.
ER -