摘要
[Objectives]The paper was to prepare immunoadjuvant nanoparticles with good photothermal conversion efficiency and to achieve the synergistic antitumor effect of phototherapy and immunotherapy.[Methods]Poly(lactic-co-glycolic acid)(PLGA)nanoparticles of imiquimod(R837)were prepared by emulsified solvent evaporation method.Dopamine was oxidized and self-polymerized to form polydopamine(PDA)under alkaline conditions,which then adhered to the surface of R837-PNPs(PDA-R837-PNPs).Particle size,Zeta potential and photothermal conversion capacity were used as indicators to select the best polymerization conditions.The photothermal conversion properties and photothermal stability of nanoparticles were investigated by near-infrared light(NIR)irradiation;the encapsulation efficiency and drug loading capacity of R837 were determined by HPLC;the cytotoxicity and cellular uptake of PDA-R837-PNPs were preliminarily investigated using 4T1 cells.[Results]PDA-R837-PNPs were prepared successfully.The optimal polymerization conditions were 0.5 mg/mL dopamine,3 h reaction time and 1.8 mg/mL R837-PNPs.The particle size of PDA-R837-PNPs was(186.7±4.81)nm;the PDI was 0.17±0.02;the Zeta potential was(-21.6±0.56)mV;the encapsulation efficiency was(58.02±0.04)%;and the drug loading capacity was(1.42±0.05)%.PDA-R837-PNPs had good photothermal conversion and photothermal stability in vitro.Cell experiments showed that PDA coating could significantly improve the celluar uptake of PNPs without obvious cytotoxicity,and PDA-R837-PNPs could produce heat to effectively kill 4T1 cells after NIR irradiation.[Conclusions]PDA-R837-PNPs have the characteristics of uniform particle size,good photothermal conversion effect and high cellular uptake rate,thus is expected to achieve efficient antitumor photoimmunotherapic effect.
基金
Supported by National Natural Science Foundation of China(82003683)
Fundamental Research Funds for the Central Universities of Southwest Minzu University(2021105)。