摘要
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.
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.
基金
supported by grants from the Ministry of Science and ICT, Republic of Korea (NRF-2018R1A2A1A05019203 and NRF-2018R1A5A2024425)
from the Korean Health Technology R&D Project (Nos. HI15C2842 and HI18C2177)
Ministry of Health & Welfare, Republic of Korea
