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

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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.
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