School of Pharmacy, Auckland Cancer Society Research Centre, Faculty of Medical & Health Sciences, University of Auckland, Auckland 1142, New Zealand.
Auckland Cancer Society Research Centre, Faculty of Medical & Health Sciences, University of Auckland, Auckland 1142, New Zealand.
Nanomedicine (Lond). 2019 Aug;14(15):1971-1989. doi: 10.2217/nnm-2018-0510. Epub 2019 Jul 29.
pH-sensitive liposomes (pSL) have emerged as promising nanocarriers due to their endo/lysosome-escape abilities, however, their pH sensitivity is compromised by poly(ethylene glycol) (PEG) coating. This study investigates whether an intracellular PEG-detachment strategy can overcome this PEG dilemma. First, PEG2000 was conjugated with a phospholipid via an acid-labile hydrazide-hydrazone bond (-CO-NH-N = CH-), which was postinserted into pSL, forming PEG-cleavable pSL (CL-PEG-pSL). Their endo/lysosomal-escape abilities in MIA PaCa-2 cells, pharmacokinetics and tumor accumulation abilities were studied using PEG-pSL as reference. CL-PEG-pSL showed rapid endo/lysosome-escape abilities in the cancer cells and higher tumor accumulation in MIA PaCa-2 xenograft model in contrast to PEG-pSL. Cleavable PEGylation is an efficient strategy to ameliorate the PEG dilemma of pSL for cancer drug delivery.
pH 敏感脂质体 (pSL) 由于其具有内体/溶酶体逃逸能力而成为有前途的纳米载体，然而，其 pH 敏感性受到聚乙二醇 (PEG) 涂层的影响。本研究探讨了一种细胞内 PEG 脱落策略是否可以克服这一 PEG 困境。首先，将 PEG2000 通过酸不稳定的腙键（-CO-NH-N=CH-）与磷脂偶联，将其插入 pSL 中，形成可切割 PEG 的 pSL (CL-PEG-pSL)。以 PEG-pSL 为对照，研究了它们在 MIA PaCa-2 细胞中的内体/溶酶体逃逸能力、药代动力学和肿瘤积累能力。与 PEG-pSL 相比，CL-PEG-pSL 在癌细胞中表现出快速的内体/溶酶体逃逸能力和更高的肿瘤积累。可切割的 PEG 化是改善 pSL 用于癌症药物递送的 PEG 困境的有效策略。
