Abstract
Aim: 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. Materials &methods: 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. Results: 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. Conclusion: Cleavable PEGylation is an efficient strategy to ameliorate the PEG dilemma of pSL for cancer drug delivery.
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