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Published on: December 1, 2016
PLGA-Lipid Hybrid Nanoparticles for Overcoming Paclitaxel Tolerance in Anoikis-Resistant Lung Cancer Cells
Sasivimon Pramual1, Kriengsak Lirdprapamongkol1,2, Korakot Atjanasuppat1,3
1Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand.
Abstract:
Drug resistance and metastasis are two major obstacles to cancer chemotherapy. During metastasis, cancer cells can survive as floating cells in the blood or lymphatic circulatory system, due to the acquisition of resistance to anoikis-a programmed cell death activated by loss of extracellular matrix attachment. The anoikis-resistant lung cancer cells also develop drug resistance. In this study, paclitaxel-encapsulated PLGA-lipid hybrid nanoparticles (PLHNPs) were formulated by nanoprecipitation combined with self-assembly. The paclitaxel-PLHNPs had an average particle size of 103.0 ± 1.6 nm and a zeta potential value of -52.9 mV with the monodisperse distribution. Cytotoxicity of the nanoparticles was evaluated in A549 human lung cancer cells cultivated as floating cells under non-adherent conditions, compared with A549 attached cells. The floating cells exhibited anoikis resistance as shown by a lack of caspase-3 activation, in contrast to floating normal epithelial cells. Paclitaxel tolerance was evident in floating cells which had an IC50 value of 418.56 nM, compared to an IC50 value of 7.88 nM for attached cells. Paclitaxel-PLHNPs significantly reduced the IC50 values in both attached cells (IC50 value of 0.11 nM, 71.6-fold decrease) and floating cells (IC50 value of 1.13 nM, 370.4-fold decrease). This report demonstrated the potential of PLHNPs to improve the efficacy of the chemotherapeutic drug paclitaxel, for eradicating anoikis-resistant lung cancer cells during metastasis.
Insights
Paclitaxel-encapsulated nanoparticles overcome drug resistance in anoikis-resistant lung cancer cells. These nanoparticles significantly enhance paclitaxel efficacy against floating cancer cells during metastasis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Drug resistance and metastasis are key challenges in cancer chemotherapy.
- Anoikis resistance, a programmed cell death evasion, enables cancer cell survival in circulation during metastasis.
- Anoikis-resistant cancer cells often exhibit cross-resistance to chemotherapeutic drugs.
Purpose of the Study:
- To develop paclitaxel-loaded PLGA-lipid hybrid nanoparticles (PLHNPs) for enhanced chemotherapy.
- To evaluate the efficacy of PLHNPs against anoikis-resistant lung cancer cells, particularly in their floating state.
Main Methods:
- Paclitaxel-PLHNPs were formulated using nanoprecipitation and self-assembly.
- Nanoparticle characterization included particle size and zeta potential measurements.
- Cytotoxicity assays were performed on A549 human lung cancer cells in both attached and floating (anoikis-resistant) conditions.
Main Results:
- Paclitaxel-PLHNPs exhibited a particle size of 103.0 ± 1.6 nm and a zeta potential of -52.9 mV.
- Floating A549 cells demonstrated anoikis resistance and significant paclitaxel tolerance (IC50 = 418.56 nM).
- Paclitaxel-PLHNPs drastically reduced IC50 values for both attached (0.11 nM) and floating (1.13 nM) cells, indicating enhanced efficacy.
Conclusions:
- PLHNPs show potential in overcoming drug resistance in anoikis-resistant lung cancer cells.
- This nanoparticle formulation can improve the therapeutic efficacy of paclitaxel against metastatic lung cancer.
- PLHNPs offer a promising strategy for targeting circulating tumor cells and enhancing cancer chemotherapy outcomes.
