Istituto per i Polimeri, Compositi e Biomateriali, Consiglio Nazionale delle Ricerche (IPCB-CNR), Viale J.F. Kennedy 54, Napoli, Italy.
Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, Napoli, Italy.
Colloids Surf B Biointerfaces. 2022 Feb;210:112240. doi: 10.1016/j.colsurfb.2021.112240. Epub 2021 Nov 24.
Here we aimed to correlate different molecular weights of hyaluronic acid (HA), 200, 800 and 1437 kDa, used to decorate poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs), to their cell uptakes. NP internalization kinetics in CD44-overexpressing breast carcinoma cells were quantified, using healthy fibroblast cells as reference. Actually, NP uptake and selectivity by tumor cells were maximized for NPs HA 800 kDa, while being minimum for NPs HA1400 kDa. This unexpected result could be explained considering that the interaction between NPs and tumor cells is dictated by rearrangement and conformation of that segment of HA chain that actually protrudes from the NPs. Overall, results obtained in this work point at how HA molecular weight, is pivotal project parameter in NP formulation to promote active targeting in the CD44 overexpressing cancer cells.
在这里，我们旨在将不同分子量的透明质酸（HA）（200、800 和 1437 kDa）与用于修饰聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒（NPs）相关联，以研究它们的细胞摄取情况。使用健康成纤维细胞作为参考，定量了在高表达 CD44 的乳腺癌细胞中 NP 的内化动力学。实际上，对于 HA800 kDa 的 NPs，其摄取和肿瘤细胞的选择性达到最大值，而对于 HA1400 kDa 的 NPs，其摄取和选择性则达到最小值。考虑到 NPs 与肿瘤细胞之间的相互作用是由实际上从 NPs 中突出的 HA 链段的重排和构象决定的，因此可以解释这一意外结果。总的来说，这项工作的结果表明，HA 分子量是 NP 配方中的关键设计参数，可促进在 CD44 过表达的癌细胞中的主动靶向。
