TY - JOUR
T1 - Polydopamine-Decorated Orlistat-Loaded Hollow Capsules with an Enhanced Cytotoxicity against Cancer Cell Lines
AU - Zhou, Xiaqing
AU - Chang, Tzu Lan
AU - Chen, Shuang
AU - Liu, Tianchi
AU - Wang, Haoyu
AU - Liang, Jun F.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Orlistat, an FDA-approved antiobesity drug, has recently been shown to have anticancer effects. However, orlistat is extremely hydrophobic with low absorption. Therefore, new approaches are needed to effectively deliver orlistat for cancer therapy. Herein, we developed a fast and simple method to use polydopamine-coated hollow capsule (PHC) as a drug nanocarrier for enhancing the therapeutic effects of orlistat. Orlistat-loaded PHC had an average size of 200 nm, which was characterized by using dynamic light scattering and scanning electron microscope. Furthermore, the polydopamine layer provided an excellent control of orlistat release because it was extremely sensitive to pH values. The cellular uptake and cytotoxicity experiments were performed to show that orlistat packaged in PHC could be endocytosed into cells and then significantly improved the cytotoxic activity against cancer cell lines in a short time compared with free orlistat. Moreover, dynamic study of cell membrane lysis was performed by staining with the LIVE/DEAD kit to demonstrate the cancer-killing mechanism. The size of the cell surface area has also been proven to be a key parameter which affected drug efficacy. Taken all together, these results present that orlistat-loaded PHC is a very promising formula for cancer treatments.
AB - Orlistat, an FDA-approved antiobesity drug, has recently been shown to have anticancer effects. However, orlistat is extremely hydrophobic with low absorption. Therefore, new approaches are needed to effectively deliver orlistat for cancer therapy. Herein, we developed a fast and simple method to use polydopamine-coated hollow capsule (PHC) as a drug nanocarrier for enhancing the therapeutic effects of orlistat. Orlistat-loaded PHC had an average size of 200 nm, which was characterized by using dynamic light scattering and scanning electron microscope. Furthermore, the polydopamine layer provided an excellent control of orlistat release because it was extremely sensitive to pH values. The cellular uptake and cytotoxicity experiments were performed to show that orlistat packaged in PHC could be endocytosed into cells and then significantly improved the cytotoxic activity against cancer cell lines in a short time compared with free orlistat. Moreover, dynamic study of cell membrane lysis was performed by staining with the LIVE/DEAD kit to demonstrate the cancer-killing mechanism. The size of the cell surface area has also been proven to be a key parameter which affected drug efficacy. Taken all together, these results present that orlistat-loaded PHC is a very promising formula for cancer treatments.
KW - cancer therapy
KW - controlled release
KW - hollow capsule
KW - nanoparticle
KW - orlistat
KW - polydopamine
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U2 - 10.1021/acs.molpharmaceut.9b00116
DO - 10.1021/acs.molpharmaceut.9b00116
M3 - Article
C2 - 31013095
AN - SCOPUS:85065804693
SN - 1543-8384
VL - 16
SP - 2511
EP - 2521
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 6
ER -