| Autor: |
Pramual S; Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand., Lirdprapamongkol K; Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand.; Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Thailand., Atjanasuppat K; Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand.; Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok 10400, Thailand., Chaisuriya P; Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand., Niamsiri N; Department of Biotechnology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand., Svasti J; Laboratory of Biochemistry, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand. |
| Abstrakt: |
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 IC 50 value of 418.56 nM, compared to an IC 50 value of 7.88 nM for attached cells. Paclitaxel-PLHNPs significantly reduced the IC 50 values in both attached cells (IC 50 value of 0.11 nM, 71.6-fold decrease) and floating cells (IC 50 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. |
