Dual pH-sensitive liposomes with low pH-triggered sheddable PEG for enhanced tumor-targeted drug delivery

被引：58
作者：
Kanamala, Manju [1 ]
Palmer, Brian D. [2 ]
Jamieson, Stephen M. F. [2 ]
Wilson, William R. [2 ]
Wu, Zimei [1 ]
机构：
[1] Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc Res Ctr, Sch Pharm, Auckland 1142, New Zealand
[2] Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc Res Ctr, Auckland 1142, New Zealand
来源：
NANOMEDICINE | 2019年 / 14卷 / 15期
关键词：
dual pH-sensitive liposomes; endosome escape; live cell imaging; MIA PaCa-2; PEG-detachment; PEG dilemma; PEG shedding; pharmacokinetics; tumor distribution; INTRACELLULAR DELIVERY; PEGYLATED LIPOSOMES; ENDOSOMAL ESCAPE; GEMCITABINE; MICELLES; CIRCULATION; STRATEGIES; CYTOTOXICITY; MECHANISMS; EFFICIENCY;
D O I：
10.2217/nnm-2018-0510
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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. [GRAPHICS] .
引用
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页码：1972 / 1990
页数：19
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