School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
J Mater Chem B. 2019 Sep 7;7(33):5115-5124. doi: 10.1039/c9tb00937j. Epub 2019 Jul 31.
The near-infrared absorbing conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) has been investigated as a contrast agent for optical and photoacoustic imaging. Lipophilic π-conjugated polymers can be efficiently encapsulated within self-assembling diblock copolymer poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles, although the effect of variations in PEG and PLGA chain lengths on nanoparticle properties, performance and biocompatibility have not yet been investigated. In this study, PEG-PLGA with different block lengths (PEG-PLGA, PEG-PLGA and PEG-PLGA) were used to encapsulate PCPDTBT. Nanoparticle sizes were smallest (<100 nm) when using PEG-PLGA, with <5% PCPDTBT content and a reduction in the total solids concentration of the organic phase. All PEG-PLGA nanoparticles were colloidally stable in water and serum-supplemented cell culture medium over 24 h at 37 °C, with slight evidence of protein surface adsorption. PEG-PLGA systems showed a threefold lower cytotoxicity (IC value) than the other two systems. Haemolytic activity was <2.5% for all systems and no platelet aggregation or inhibition of ADP-induced platelet aggregation was observed. Encapsulation of PCPDTBT within a PEG-PLGA matrix shifted fluorescence emission towards red wavelengths (760 nm in THF vs. 840 nm in nanoparticles) and reduced the quantum yield by 30-70-fold compared to THF. Nonetheless, PCPDTBT:PEG-PLGA systems had a marginally higher quantum yield and signal-to-background ratio in a phantom mouse compared with PEG-PLGA and PEG-PLGA systems. As a photoacoustic imaging probe, PCPDTBT:PEG-PLGA systems also showed a higher photoacoustic amplitude compared to higher molecular weight PEG-PLGA systems. Overall, the low molecular weight PEG-PLGA nanoparticle systems conferred the benefits of smaller sizes, reduced cytotoxicity and enhanced imaging performance compared to higher molecular weight matrix polymers.
近红外吸收共轭聚合物聚[2,6-(4,4-双-(2-乙基己基)-4H-环戊[2,1-b;3,4-b']-二噻吩)-交替-4,7-(2,1,3-苯并噻二唑)]（PCPDTBT）已被研究作为光学和光声成像的对比剂。亲脂性π共轭聚合物可以有效地封装在自组装二嵌段共聚物聚乙二醇甲基醚-聚（乳酸-共-乙醇酸）（PEG-PLGA）纳米粒子中，尽管 PEG 和 PLGA 链长的变化对纳米粒子性质、性能和生物相容性的影响尚未得到研究。在这项研究中，使用不同链长的 PEG-PLGA（PEG-PLGA、PEG-PLGA 和 PEG-PLGA）来封装 PCPDTBT。当使用 PEG-PLGA 时，纳米粒子的尺寸最小（<100nm），PCPDTBT 的含量<5%，并且有机相的总固体浓度降低。所有 PEG-PLGA 纳米粒子在水和血清补充的细胞培养基中在 37°C 下 24 小时内均具有胶体稳定性，只有轻微的蛋白质表面吸附证据。PEG-PLGA 体系的细胞毒性（IC 值）比其他两种体系低三倍。所有体系的溶血活性均<2.5%，未观察到血小板聚集或 ADP 诱导的血小板聚集抑制。PCPDTBT 封装在 PEG-PLGA 基质中会将荧光发射移向红光波长（THF 中为 760nm，纳米粒子中为 840nm），并使量子产率降低 30-70 倍，与 THF 相比。尽管如此，与 PEG-PLGA 和 PEG-PLGA 体系相比，PCPDTBT:PEG-PLGA 体系在幻影小鼠中仍具有更高的量子产率和信号背景比。作为光声成像探针，与高分子量 PEG-PLGA 体系相比，PCPDTBT:PEG-PLGA 体系也表现出更高的光声幅度。总的来说，与高分子量基质聚合物相比，低分子量 PEG-PLGA 纳米粒子体系具有更小的尺寸、更低的细胞毒性和增强的成像性能的优势。
