Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle

• 来源期刊: 药学学报（英文版）
• 关键词: Safety Photochemotherapy Biopolymeric nanoparticle Poly(γ-glutamic acid) Polymerized dopamine Paclitaxel
• 年，卷（期）: 2019,（3）
• 页码范围: 565-574
• 页数: 10页
• 语种: 英文

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 PDA-coated,amphiphilic γ-PGA-based micelles (AM) carrying PTX (PDA/AM/P) exerted near-infrared-responsive 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.