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Liposomal nanoparticle mediated chemo-phototherapy for breast cancer ablation via boldine driven metabolic
Pramit Kumar Ghosh1, Sajmina Khatun1, Sandip Das2
1Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, 502284, India.
Abstract:
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive phenotype, molecular heterogeneity, and lack of specific therapeutic targets. To address these limitations and align with emerging personalized medicine strategies, a multifunctional liposomal nanocarrier (RELIB) was developed to co-encapsulate the chemotherapeutic alkaloid Boldine and the near-infrared (NIR)-responsive photothermal dye IR775, enabling combined chemo-photothermal therapy with tunable therapeutic potential. RELIB nanoparticles (RELIB NPs) (∼200 nm) demonstrated high encapsulation efficiency and effective photothermal conversion under NIR irradiation. In vitro studies in 4T1 cells revealed enhanced cellular internalization, selective cytotoxicity, induction of apoptosis, mitochondrial membrane depolarization, DNA damage, and inhibition of migration and clonogenic survival. Importantly, RELIB exhibited favorable biocompatibility in Zebrafish (Danio rerio) and Drosophila melanogaster models. In vivo evaluation in 4T1 tumor-bearing mice showed significant tumor regression upon NIR irradiation, with minimal systemic toxicity. Metabolomic profiling further indicated reprogramming of key pathways involved in apoptotic signaling and tumor suppression, suggesting the potential to use metabolic signatures to guide treatment response. Notably, Boldine conferred cyto-protection in normal cells, preserving cellular homeostasis and highlighting the platform's selective targeting capacity. Collectively, these findings position RELIB as a promising, biocompatible, and adaptable nanotherapeutic system with strong potential for personalized intervention in TNBC.
Insights
A novel nanocarrier, RELIB, combines chemotherapy and photothermal therapy for triple-negative breast cancer (TNBC). This dual-action approach shows significant tumor reduction and good biocompatibility in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and lack of targeted treatments.
- Personalized medicine strategies are crucial for improving TNBC patient outcomes.
Purpose of the Study:
- To develop a multifunctional liposomal nanocarrier (RELIB) for combined chemo-photothermal therapy in TNBC.
- To evaluate the efficacy and biocompatibility of RELIB for personalized TNBC intervention.
Main Methods:
- Co-encapsulation of Boldine (chemotherapeutic) and IR775 (NIR-responsive dye) into liposomal nanoparticles (RELIB NPs).
- In vitro assessment of cellular uptake, cytotoxicity, apoptosis, DNA damage, and migration in 4T1 cells.
- In vivo studies in tumor-bearing mice and biocompatibility tests in Zebrafish and Drosophila melanogaster models.
- Metabolomic profiling to analyze treatment response pathways.
Main Results:
- RELIB NPs demonstrated efficient photothermal conversion and enhanced cellular internalization.
- Significant in vitro cytotoxicity, apoptosis induction, and inhibition of tumor cell migration and survival were observed.
- In vivo studies showed substantial tumor regression with minimal systemic toxicity.
- Boldine provided cytoprotection to normal cells, indicating selective targeting.
Conclusions:
- RELIB is a promising, biocompatible nanotherapeutic system for combined chemo-photothermal therapy in TNBC.
- The system exhibits tunable therapeutic potential and selective targeting capabilities.
- Metabolic profiling may guide personalized treatment strategies for TNBC.
