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Kojic Acid Dipalmitate-Loaded Nanoparticles for the Treatment of Triple-Negative Breast Cancer
Julia Capp Zilles1,2, Onyinyechi Obidiro1, Gantumur Battogtokh1
1Center for Drug Research and Development, Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA.
Introduction:
Triple-negative breast cancer (TNBC) is responsible for 10-20% of breast cancer cases and is associated with poor prognosis and limited treatment options due to the lack of expression of hormone and HER2 receptors. Kojic acid dipalmitate (KDP) is best known for its skin depigmenting activity; however kojic acid derivatives have shown promising antitumor activity. Such potential remains unexplored for KDP in breast cancer.
Methods:
KDP-loaded nanoparticles were developed by in situ dispersion polymerization, using polylactide (PLA: a biodegradable and biocompatible polyester) as a macromonomer and a pH-sensitive acetal crosslinker. The nanoparticles were characterized and tested in TNBC cells.
Results And Discussion:
The nanoparticles had a spherical morphology, a hydrodynamic diameter of approximately 240 nm with homogeneous size distribution, a negative zeta potential, and a drug loading of 0.61% ± 0.06 (w/w), in accordance with the drug loading theoretical value, with 100% encapsulation efficiency. FT-IR confirmed KDP incorporation into the nanoparticle. Nanoparticles were stable for 90 days (room temperature and 4°C storage). Cell viability studies with the TNBC cell line (MDA-MB-231) showed a significant, concentration-dependent reduction in cell viability following treatment with KDP-loaded nanoparticles, with an IC50 value of 2.04 μM at 48 hours, while blank nanoparticles were non-cytotoxic. In vitro cellular uptake studies with rhodamine 123-loaded nanoparticles demonstrated internalization of the nanoparticles after 1 hour, and a progressive accumulation in the perinuclear region up to 48 hours, consistent with the cytotoxicity plateau observed at longer exposure times.
Conclusion:
These findings highlight the novelty of pH-sensitive KDP-loaded polymeric nanoparticles and support suitability as a nanocarrier platform for poorly soluble drugs like KDP in triple-negative breast cancer research.
Insights
New pH-sensitive nanoparticles effectively deliver kojic acid dipalmitate (KDP) to triple-negative breast cancer (TNBC) cells, significantly reducing viability. This offers a promising new nanocarrier platform for TNBC treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic options.
- Kojic acid derivatives show potential antitumor activity, but their application in breast cancer remains largely unexplored.
- Kojic acid dipalmitate (KDP), known for skin depigmentation, has unexplored potential against TNBC.
Purpose of the Study:
- To develop and characterize novel pH-sensitive polymeric nanoparticles for the delivery of kojic acid dipalmitate (KDP).
- To evaluate the efficacy of KDP-loaded nanoparticles against triple-negative breast cancer (TNBC) cells in vitro.
- To establish KDP-loaded nanoparticles as a potential nanocarrier platform for TNBC therapy.
Main Methods:
- KDP-loaded nanoparticles were synthesized using in situ dispersion polymerization with polylactide (PLA) and a pH-sensitive acetal crosslinker.
- Nanoparticles were characterized for morphology, size, zeta potential, drug loading, and stability.
- In vitro cytotoxicity and cellular uptake studies were performed using the MDA-MB-231 TNBC cell line.
Main Results:
- Synthesized nanoparticles exhibited spherical morphology, ~240 nm size, negative zeta potential, and 100% encapsulation efficiency of KDP.
- KDP-loaded nanoparticles demonstrated significant, concentration-dependent cytotoxicity against TNBC cells (IC50 = 2.04 μM at 48h), with blank nanoparticles showing no toxicity.
- In vitro studies confirmed nanoparticle internalization and progressive accumulation within TNBC cells, correlating with observed cytotoxicity.
Conclusions:
- pH-sensitive KDP-loaded polymeric nanoparticles represent a novel formulation for targeting TNBC.
- The developed nanocarrier platform demonstrates suitability for delivering poorly soluble drugs like KDP in TNBC research.
- These findings support the potential of KDP-loaded nanoparticles as a therapeutic strategy for triple-negative breast cancer.
