Pedersbæk Dennis, Krogager Louise, Albertsen Camilla Hald, Ringgaard Lars, Hansen Anders E, Jønsson Katrine, Larsen Jannik B, Kjær Andreas, Andresen Thomas L, Simonsen Jens B
Department of Health Technology, Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, 2100 Copenhagen, Denmark.
ACS Omega. 2020 Dec 21;6(1):871-880. doi: 10.1021/acsomega.0c05468. eCollection 2021 Jan 12.
Biomimetic high-density lipoproteins (b-HDL) have in the past two decades been applied for various drug delivery applications. As b-HDL inherently have relatively long circulation half-life and high tumor accumulation, this has inspired researchers to use b-HDL to selectively deliver drugs to tumors. PEGylation of the b-HDL has been pursued to increase the circulation half-life and therapeutic efficacy even further. The b-HDL consist of lipids stabilized by a protein/peptide scaffold, and while PEGylation of the scaffold has been shown to greatly increase the circulation half-life of the scaffold, the effect of PEGylation of the lipids is much less significant. Still, it remains to be evaluated how the biological fate, including cellular uptake, biodistribution, and circulation half-life, of the b-HDL lipids is affected by PEGylation of the b-HDL scaffold. We studied this with apolipoprotein A-I (apoA-I)-based b-HDL and mono-PEGylated b-HDL (PEG b-HDL) both and . We found that PEGylation of the b-HDL scaffold only seemed to have minimal effect on the biological fate of the lipids. Both b-HDL and PEG b-HDL overall shared similar biological fates, which includes cellular uptake through the scavenger receptor class B type 1 (SR-BI) and relatively high tumor accumulation. This highlights that b-HDL are dynamic particles, and the biological fates of the b-HDL components (lipids and scaffold) can differ. A phenomenon that may also apply for other multicomponent nanoparticles.
在过去二十年中，仿生高密度脂蛋白（b-HDL）已被应用于各种药物递送应用。由于b-HDL本身具有相对较长的循环半衰期和较高的肿瘤蓄积性，这激发了研究人员使用b-HDL将药物选择性地递送至肿瘤。人们一直在对b-HDL进行聚乙二醇化修饰，以进一步延长其循环半衰期并提高治疗效果。b-HDL由通过蛋白质/肽支架稳定的脂质组成，虽然已证明对支架进行聚乙二醇化修饰可大大延长支架的循环半衰期，但对脂质进行聚乙二醇化修饰的效果则要小得多。尽管如此，b-HDL支架的聚乙二醇化修饰如何影响b-HDL脂质的生物学命运，包括细胞摄取、生物分布和循环半衰期，仍有待评估。我们使用基于载脂蛋白A-I（apoA-I）的b-HDL和单聚乙二醇化b-HDL（PEG b-HDL）对此进行了研究。我们发现，b-HDL支架的聚乙二醇化修饰似乎对脂质的生物学命运影响甚微。b-HDL和PEG b-HDL总体上具有相似的生物学命运，包括通过B1型清道夫受体（SR-BI）进行细胞摄取以及相对较高的肿瘤蓄积性。这突出表明b-HDL是动态颗粒，并且b-HDL各组分（脂质和支架）的生物学命运可能不同。这种现象可能也适用于其他多组分纳米颗粒。
