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Published on: February 19, 2016
Self-assembled nanoparticles of alginate and paclitaxel-triphenylphosphonium for mitochondrial apoptosis targeting
Mehdi Esfandyari-Manesh1, Bahar Morshedi2, Parisa Joolaie2
1Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. mesfandyari@sina.tums.ac.ir.
Abstract:
Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around - 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.
Insights
This study developed novel paclitaxel-triphenylphosphonium nanoparticles to target mitochondria in breast cancer cells. These nanoparticles significantly enhanced apoptosis and inhibited cancer cell growth compared to free paclitaxel.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Paclitaxel (PTX) is an antimitotic drug effective against breast cancer by inducing apoptosis.
- Mitochondria play a crucial role in initiating apoptosis signaling pathways.
- Targeting mitochondria can enhance the efficacy of chemotherapy drugs like PTX.
Purpose of the Study:
- To synthesize and characterize a novel PTX-TPP prodrug encapsulated in self-assembled alginate nanoparticles.
- To evaluate the enhanced mitochondrial apoptosis induction and cytotoxicity of PTX-TPP nanoparticles in breast cancer cells.
- To investigate the potential of this targeted nanoparticle system for breast cancer treatment.
Main Methods:
- Synthesis of PTX-TPP prodrug using a pH-sensitive ester bond.
- Encapsulation of PTX-TPP into alginate nanoparticles via ionotropic complexation.
- Characterization of nanoparticle size, zeta potential, and drug loading.
- In vitro evaluation of cytotoxicity and apoptosis induction in MCF7 breast cancer cells.
Main Results:
- PTX-TPP prodrug was successfully synthesized and encapsulated in alginate nanoparticles (123 nm size, -25.8 Mv zeta potential, 16.5% loading).
- PTX-TPP nanoparticles exhibited a 6.3-fold higher cytotoxicity (lower IC50) against MCF7 cells compared to free PTX.
- Treatment with PTX-TPP nanoparticles resulted in significantly higher early and late apoptotic/necrotic cell populations (11.6-fold and 3.9-fold increase, respectively).
Conclusions:
- Mitochondrial-targeted PTX-TPP nanoparticles demonstrate enhanced anti-cancer efficacy.
- Self-assembled alginate nanoparticles are a promising delivery system for improving PTX-based breast cancer therapy.
- This approach offers a strategy to overcome limitations of conventional chemotherapy by enhancing targeted apoptosis induction.
