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Development of Multifunctional Targeted Dual-Loaded Polymeric Nanoparticles for Triple-Negative Breast Cancer
Gantumur Battogtokh1, Emmanuel O Akala1
1Center for Drug Research and Development, Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA.
Pharmaceutics
|April 26, 2025
Summary
New dual-loaded nanoparticles target triple-negative breast cancer (TNBC) effectively. Cetuximab-targeted nanoparticles loaded with cisplatin and paclitaxel show promise for improved TNBC treatment, overcoming current therapy limitations.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature and resistance to conventional therapies.
- Current treatment modalities for TNBC often suffer from limited efficacy, systemic toxicity, and poor drug delivery specificity.
- Developing advanced therapeutic strategies is crucial for improving outcomes in TNBC patients.
Purpose of the Study:
- To engineer a novel dual-loaded targeted nanotherapeutic system for enhanced treatment of triple-negative breast cancer.
- To address the limitations of conventional TNBC therapies, including efficacy, toxicity, and site-specific delivery.
- To create nanoparticles capable of delivering both cisplatin and paclitaxel specifically to TNBC cells.
Main Methods:
- Synthesis and characterization of PEGylated methacrylate-polylactide copolymer nanoparticles encapsulating cisplatin.
- Fabrication of dual-loaded nanoparticles incorporating paclitaxel with controlled drug loading.
- Surface functionalization of nanoparticles with Cetuximab (CTX) for targeted delivery to EGFR-expressing TNBC cells.
- In vitro evaluation of nanoparticle characteristics, cellular uptake, and cytotoxicity in MDA-MB-231 TNBC cells.
Main Results:
- Fabricated nanoparticles exhibited homogenous size (198 nm) and negative zeta potential (-41.3 mV) with 1.33% drug loading.
- CTX-targeted nanoparticles demonstrated enhanced cellular uptake and significantly higher cytotoxicity compared to non-targeted nanoparticles and free drugs.
- The IC50 of CTX-targeted nanoparticles was 0.1 μM, substantially lower than p-NPs (0.49 μM) and free drugs (0.57 μM) after 96 hours.
Conclusions:
- CTX-targeted polymeric nanoparticles effectively co-deliver cisplatin and paclitaxel for potential TNBC therapy.
- The developed nanotherapeutic system shows significant potential in overcoming the challenges associated with treating triple-negative breast cancer.
- Further in vivo investigations are warranted to validate the therapeutic efficacy of these targeted nanoparticles.
