TY - JOUR
T1 - Folic acid-modified bovine serum albumin nanoparticles with doxorubicin and chlorin e6 for effective combinational chemo-photodynamic therapy
AU - Lee, Hoomin
AU - Kim, Suji
AU - Oh, Cheolwoo
AU - Khan, Imran
AU - Shukla, Shruti
AU - Bajpai, Vivek K.
AU - Han, Young Kyu
AU - Huh, Yun Suk
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/12
Y1 - 2020/12
N2 - We herein describe a facile method to synthesize stable bovine serum albumin-based nanoparticles (BNPs) loaded with two anticancer therapeutics, doxorubicin (DOX) and a photosensitizer, chlorin e6 (Ce6), in combination with folic acid (FA) as a target cancer cell receptor for the development of an effective combined chemo and photodynamic (FA-Ce6/DOX/BNPs) therapy against cervical cancer. FA-Ce6/DOX/BNPs exhibited excellent monodispersity with an average diameter of 103.5 ± 3.8 nm, a negative zeta potential of approximately −30.44 ± 0.35 mV, and long-term stability. As a result, FA-Ce6/DOX/BNPs exhibited severe toxicity to cervical HeLa cancer cells. Also, a higher drug release rate was observed under acidic pH conditions (pH 5.0). Moreover, FA-Ce6/DOX/BNPs potentiated mitochondrial reactive oxygen species (ROS) production in HeLa cells under 671-nm laser exposure, leading to activation of key regulator proteins of apoptosis such as BH3 interacting-domain death agonist (BID), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (BAX), as well as induction of the caspase cascade and mitochondrial ROS-mediated cell death. Confocal microscopy analysis further validated cellular uptake of FA-Ce6/DOX/BNPs by HeLa cells. Furthermore, results of real-time quantitative PCR (RT-qPCR) and western blot analysis further validated the anticancer effect of FA-Ce6/DOX/BNPs, as evidenced by elevated gene/protein expression levels of apoptotic biomarkers p53, BID, caspase-3, cleaved poly(ADP-ribose) polymerase 1 (PARP-1), and BAX, contrary to levels of the anti-apoptotic marker Bcl-2. Moreover, in vivo toxicity results of FA-Ce6/DOX/BNPs using laser irradiation in zebrafish larvae, as a chemo-photodynamic therapy confirmed that it does not affect the larval development without causing any adverse toxic effect in zebrafish larvae. Altogether these findings strongly support the anticancer effect of FA-Ce6/DOX/BNPs combinational chemo-photodynamic therapy, which could be a promising candidate for cervical cancer therapy.
AB - We herein describe a facile method to synthesize stable bovine serum albumin-based nanoparticles (BNPs) loaded with two anticancer therapeutics, doxorubicin (DOX) and a photosensitizer, chlorin e6 (Ce6), in combination with folic acid (FA) as a target cancer cell receptor for the development of an effective combined chemo and photodynamic (FA-Ce6/DOX/BNPs) therapy against cervical cancer. FA-Ce6/DOX/BNPs exhibited excellent monodispersity with an average diameter of 103.5 ± 3.8 nm, a negative zeta potential of approximately −30.44 ± 0.35 mV, and long-term stability. As a result, FA-Ce6/DOX/BNPs exhibited severe toxicity to cervical HeLa cancer cells. Also, a higher drug release rate was observed under acidic pH conditions (pH 5.0). Moreover, FA-Ce6/DOX/BNPs potentiated mitochondrial reactive oxygen species (ROS) production in HeLa cells under 671-nm laser exposure, leading to activation of key regulator proteins of apoptosis such as BH3 interacting-domain death agonist (BID), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (BAX), as well as induction of the caspase cascade and mitochondrial ROS-mediated cell death. Confocal microscopy analysis further validated cellular uptake of FA-Ce6/DOX/BNPs by HeLa cells. Furthermore, results of real-time quantitative PCR (RT-qPCR) and western blot analysis further validated the anticancer effect of FA-Ce6/DOX/BNPs, as evidenced by elevated gene/protein expression levels of apoptotic biomarkers p53, BID, caspase-3, cleaved poly(ADP-ribose) polymerase 1 (PARP-1), and BAX, contrary to levels of the anti-apoptotic marker Bcl-2. Moreover, in vivo toxicity results of FA-Ce6/DOX/BNPs using laser irradiation in zebrafish larvae, as a chemo-photodynamic therapy confirmed that it does not affect the larval development without causing any adverse toxic effect in zebrafish larvae. Altogether these findings strongly support the anticancer effect of FA-Ce6/DOX/BNPs combinational chemo-photodynamic therapy, which could be a promising candidate for cervical cancer therapy.
KW - Biodegradable BNPs
KW - Drug delivery system
KW - Mitochondrial apoptosis
KW - Photodynamic therapy
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85089560134&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2020.111343
DO - 10.1016/j.msec.2020.111343
M3 - Article
C2 - 32919690
AN - SCOPUS:85089560134
SN - 0928-4931
VL - 117
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
M1 - 111343
ER -