Biomedical Physics Laboratory of National Cancer Institute, Baublio 3B, LT-08406 Vilnius, Lithuania.
Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-10257 Vilnius, Lithuania.
ACS Appl Mater Interfaces. 2021 Aug 25;13(33):39076-39087. doi: 10.1021/acsami.1c10618. Epub 2021 Aug 11.
Fluorophores with multifunctional properties known as rare-earth-doped nanoparticles (RENPs) are promising candidates for bioimaging, therapy, and drug delivery. When applied , these nanoparticles (NPs) have to retain long blood-circulation time, bypass elimination by phagocytic cells, and successfully arrive at the target area. Usually, NPs in a biological medium are exposed to proteins, which form the so-called "protein corona" (PC) around the NPs and influence their targeted delivery and accumulation in cells and tissues. Different surface coatings change the PC size and composition, subsequently deciding the fate of the NPs. Thus, detailed studies on the PC are of utmost importance to determine the most suitable NP surface modification for biomedical use. When it comes to RENPs, these studies are particularly scarce. Here, we investigate the PC composition and its impact on the cellular uptake of citrate-, SiO-, and phospholipid micelle-coated RENPs (LiYF:Yb,Tm). We observed that the PC of citrate- and phospholipid-coated RENPs is relatively stable and similar in the adsorbed protein composition, while the PC of SiO-coated RENPs is larger and highly dynamic. Moreover, biocompatibility, accumulation, and cytotoxicity of various RENPs in cancer cells have been evaluated. On the basis of the cellular imaging, supported by the inhibition studies, it was revealed that RENPs are internalized by endocytosis and that specific endocytic routes are PC composition dependent. Overall, these results are essential to fill the gaps in the fundamental understanding of the nano-biointeractions of RENPs, pertinent for their envisioned application in biomedicine.
具有多功能特性的荧光团，即稀土掺杂纳米粒子（RENPs），是生物成像、治疗和药物输送的有前途的候选者。当应用这些纳米粒子（NPs）时，它们必须保持长时间的血液循环，避免被吞噬细胞清除，并成功到达目标区域。通常，生物介质中的 NPs 会暴露于蛋白质中，这些蛋白质会在 NPs 周围形成所谓的“蛋白质冠（PC）”，并影响它们在细胞和组织中的靶向输送和积累。不同的表面涂层会改变 PC 的大小和组成，从而决定 NPs 的命运。因此，对 PC 的详细研究对于确定最适合生物医学用途的 NP 表面改性至关重要。对于 RENPs 来说，这些研究尤其稀缺。在这里，我们研究了 PC 的组成及其对柠檬酸、SiO2 和磷脂胶束包覆的 RENPs（LiYF:Yb，Tm）细胞摄取的影响。我们观察到，柠檬酸和磷脂包覆的 RENPs 的 PC 相对稳定，吸附蛋白组成相似，而 SiO2 包覆的 RENPs 的 PC 较大且高度动态。此外，还评估了各种 RENPs 在癌细胞中的生物相容性、积累和细胞毒性。基于细胞成像，并通过抑制研究得到支持，揭示了 RENPs 通过内吞作用被内化，并且特定的内吞途径依赖于 PC 的组成。总的来说，这些结果对于填补对 RENPs 纳米生物相互作用的基本理解的空白至关重要，这对于它们在生物医学中的预期应用至关重要。
