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(1.Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing400016, China; 2.Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing400010, China; 3.Chongqing Key Laboratory of Ultrasound and Engineering,Chongqing 400016, China; 4.Department of Obstetrics and Gynecology,Second Affiliated Hospital of Chongqing MedicalUniversity, Chongqing 400010, China)



·基础与实验研究·

Preparation and characteristic comparison of two phase-transition multifunctional nanoparticles

TANGQin1,2，3,ZHUShenyin1*,CHANGShufang4,CUIJianyu1,2,TIANZhonghua1,SUNJiangchuan4,WANGZhigang2,QIUFeng1

(1.DepartmentofPharmacy,FirstAffiliatedHospitalofChongqingMedicalUniversity,Chongqing400016,China; 2.InstituteofUltrasoundImaging,ChongqingMedicalUniversity,Chongqing400010,China; 3.ChongqingKeyLaboratoryofUltrasoundandEngineering,Chongqing400016,China; 4.DepartmentofObstetricsandGynecology,SecondAffiliatedHospitalofChongqingMedicalUniversity,Chongqing400010,China)

Objective To prepare two multifunctional nanoparticles loaded with indocyanine green (ICG) and liquid fluorocarbon (perfluoropentane [PFP] or perfluorohexane [PFH]), and compare their physicochemical properties, stability phase-transition and imaging capacity in vitro. Methods The PLGA nanoparticles loaded with ICG and PFP or PFH (IPNPs or IHNPs) were prepared using a modified double emulsion technique, and then the physicochemical properties, stability and phase-transition under heating, laser irradiation, LIFU exposure and photoacoustic imaging capacity were compared. Results There were no significant differences between the IPNPs and IHNPs about their physicochemical properties, including size ([490.53±36.96]nm vs [512.23±38.52]nm), zeta potential ([-14.40±1.40]mV vs [-13.97±1.61]mV) and absorption spectrum, and both of them were stable within 24 h. The phase-transition energy under different situations was significantly lower in IPNPs group compared with IHNPs. In addition, the ultrasonic and photoacoustic imaging capacity obviously increased in IPNPs. The cell viability was higher in IPNPs phase-transition irradiation with laser energy than that in IHNPs ([95.34±7.96]% vs [54.92±6.11]%,P<0.05). Conclusion IPNPs might be a more promising multifunctional platform for theranostics.

Multifunctional nanoparticles; Fluorocarbons; Phase-transition; Imaging

近年来，纳米医学技术的多功能化，可将显像诊断剂与治疗药物整合于同一给药系统，形成一种新的治疗诊断型多功能分子影像探针，实现医学成像引导下的可视化诊疗[1-4]，且随着该领域研究的深入，多功能造影剂可实现多模态成像，以弥补现有成像方式的不足。传统超声微泡造影剂为诊疗一体化的发展起到了巨大推动作用，但其粒径过大、不易穿过血管内皮间隙及不稳定等性质限制了其作为诊疗探针的应用与发展[3]。相变型高分子纳米粒的出现为诊疗一体化的发展提供了新的可能。目前常用的相变材料为液态氟碳化合物，其中以低沸点的液态全氟正戊烷(perfluoropentane, PFP)及全氟己烷(perfluorohexane, PFH)最为常用，沸点分别为29℃和56℃，在常温下均为液态，外界压力减小至气化压力阈值或温度升高至沸点以上时，可发生液气相转变，可用于超声、MRI等成像[5-6]。液态氟碳纳米粒可同时携载治疗药物，转运至治疗部位达到诊疗一体化的目的。吲哚菁绿(indocyanine green, ICG)是美国及我国食品药品监督管理局批准应用于临床的显像和诊断剂，其在近红外光区有最大光吸收，可作为良好的荧光探针实现对深部病变组织准确灵敏的显影。此外，ICG也作为光敏物质广泛应用于光动力疗法及光热疗法的研究[7-9]。

若将液态氟碳及ICG同时包载于乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid)carboxyl, PLGA)]中制备成纳米级微球，体外给予激光辐照，ICG吸收光能转变为热能，使液态氟碳发生相变，可实现多模态成像，同时产生活性氧和热效应发挥治疗作用，是一种非常有前景的多功能诊疗制剂。……