Original articles
Dongyoon Kim, Quoc-Viet Le, Young Bong Kim, Yu-Kyoung Oh. Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle[J]. Acta Pharmaceutica Sinica B, 2019, 9(3): 565-574

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle
Dongyoon Kima, Quoc-Viet Lea, Young Bong Kimb, Yu-Kyoung Oha
a College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea;
b Department of Biomedical Engineering, Konkuk University, Seoul 05029, Republic of Korea
The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid) (γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel (PTX) to form PTX-encapsulated micelles. The surfaces of PTX-loaded micelles were then coated with polymerized dopamine (PDA). The PDAcoated, amphiphilic γ-PGA-based micelles (AM) carrying PTX (PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.
Key words:    Safety    Photochemotherapy    Biopolymeric nanoparticle    Poly(γ-glutamic acid)    Polymerized dopamine    Paclitaxel   
Received: 2018-10-01     Revised:
DOI: 10.1016/j.apsb.2019.01.005
Funds: This research was supported by grants from the Ministry of Science and ICT, Republic of Korea (NRF-2018R1A2A1A05019203 and NRF-2018R1A5A2024425) and from the Korean Health Technology R&D Project (Nos. HI15C2842 and HI18C2177), Ministry of Health & Welfare, Republic of Korea.
Corresponding author: Yu-Kyoung Oh     Email:ohyk@snu.ac.kr
Author description:
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Dongyoon Kim
Quoc-Viet Le
Young Bong Kim
Yu-Kyoung Oh

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