Abstract
Liposomes are well-investigated drug or gene delivery vehicles for chemotherapy, used by taking advantage of their biocompatibility and biodegradability. A central question on the construction of intracellular liposomal delivery systems is to entrap the liposomes of interest in the highly acidic and proteolytic endosomal environment. In the other words, it is essential that the liposomes release a therapeutic drug into the cytosol before they are degraded in the endosome. As a strategy to enhance the endosome escape, the self-lytic liposomes with acidic pH-selective membrane active polypeptide are considered highly effective. Here, an acidic pH-selective membrane-lytic polypeptide (LPE) and its retro isomer (rLPE) were designed, and then their membrane-lytic activities against EggPC liposomes were determined. It was noticed that the rLPE polypeptide showed an increase in activity compared with the LPE polypeptide. Furthermore, the rLPE polypeptide was conjugated to liposomes via a flexible Gly-Gly-Gly-Gly linker to facilitate the pH-selective content release. The rLPE anchoring liposomes exhibited distinctly different contents release behavior at physiological and endosomal pHs, namely typical contents release from liposomes was positively observed at acidic pH range. The overarching goal of this paper is to develop efficient pH-selective therapeutic delivery systems by using our findings.
Highlights
Liposomes are artificial spherical vesicles with a bilayered membrane structure formed with the self-assembly of nontoxic phospholipids in aqueous solution [1,2,3]
We examined the dependence of a variety of pH on the calcein release from rLPE polypeptide and stearic acid conjugate (rLPE-St) anchoring liposoms
We presented the design and characterization of the melittin mimetic pH-selective lytic polypeptide LPE and its retro isomer
Summary
Liposomes are artificial spherical vesicles with a bilayered membrane structure formed with the self-assembly of nontoxic phospholipids in aqueous solution [1,2,3]. Their lipid bilayer of liposomal vesicles enables their efficacy as drug delivery carriers due to their versatile nature in encapsulating both hydrophobic and hydrophilic drugs within nonpolar bilayer regions of the membrane and the aqueous core, respectively [4]. The contents release from liposomes is generally achieved through a passive mechanism. Demand for the construction of liposome-based systems that include mechanisms to facilitate suitable stimuli-responsive contents release can be expected to increase. Tumor cells are slightly more acidic than normal cells [8,9]
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