基于硬脂酸修饰的聚(己二酸甘油酯)(PGAS)的生物可降解纳米颗粒是有前途的药物递送载体。为了研究颗粒界面特征对生物命运的影响,PGAS纳米颗粒共价和非共价涂覆有N-(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物。HPMA共聚物改性的PGAS纳米颗粒具有相似的粒径,但负zeta电位较少。纳米粒子用荧光染料DiR(非共价)和DYOMICS-676(共价结合到HPMA共聚物)进行双重标记,并通过多光谱光学成像对其生物分布进行非侵入性研究。共价和非共价涂层都会导致健康和荷瘤小鼠的药代动力学和生物分布发生变化。除了预期的肿瘤积累,在其他器官中也观察到两种荧光染料的高信号,包括肝脏,卵巢,肾上腺,还有骨头.纳米载体的意外积累需要进一步详细和系统的研究,特别是关于观察到的卵巢和肾上腺积累。
Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate) (PGAS) are promising carriers for drug delivery. In order to investigate the impact of the particle interface characteristics on the biological fate, PGAS nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have similar particle sizes, but less negative zeta-potentials. Nanoparticles are double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676 (covalently bound to HPMA copolymer), and their biodistribution is investigated noninvasively by multispectral optical imaging. Both covalent and noncovalent coatings cause changes in the pharmacokinetics and biodistribution in healthy and tumor-bearing mice. In addition to the intended tumor accumulation, high signals of both fluorescent dyes are also observed in other organs, including liver, ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers needs further detailed and systematic investigations, especially with respect to the observed ovarian and adrenal gland accumulation.