Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells

Abstract

Liposomes have been extensively used as effective nanocarriers, providing better solubility, higher stability and slower release of drugs compared to free drug administration. They are also preferred due to their nontoxic nature as well as their biodegradability and cell membrane mimicking abilities. In this study, we examined noncovalent integration of a cell penetrating arginine-rich peptide amphiphile into a liposomal formulation of negatively charged 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DOPG) phospholipids in the presence of cholesterol due to its amphipathic character. We studied changes in the physical characteristics (size, surface potential and membrane polarity) of the liposomal membrane, as well as in the encapsulation of hydrophilic and hydrophobic agents due to peptide amphiphile incorporation. The activities of peptide integrated liposomal systems as drug delivery agents were investigated by using anticancer drugs, doxorubicin-HCI and paclitaxel. Enhancement in liposomal uptake due to arginine-rich peptide integration, and enhanced efficacy of the drugs were observed with peptide functionalized liposomes compared to free drugs.

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery

“…The amphipathic properties of the peptide eliminated the need for crosslinking methods used for integration into liposome formulations [33]. The effectiveness of peptide integrated liposomal system as drug delivery platforms was investigated by using the anticancer drugs doxorubicin-HCl and paclitaxel.…”

“…The aim was to take advantage of the process by which certain pathogens can cross the blood-brain barrier (BBB) in a transcellular or paracellular manner. In vivo imaging results and cellular uptake indicated that EPRNEEK peptide-modified NPs showed enhanced brain tumor–targeting activity compared to a pentapeptide derived from endogenous laminin [33, 74]. …”

“…Sardan et al designed an arginine-rich cell-penetrating amphiphilic peptide (lauryl–PPPPRRRR–Am), which was integrated into a liposome formulation (DOPG) in order to target the activity of anticancer agents (doxorubicin-HCl and paclitaxel) inside MCF7 breast cancer cells. Arginine PA integrated on liposomes enhanced the uptake of model reagents by MCF7 breast cancer cells compared to native liposomes and free reagents [33]. Both hydrophilic (i.e., rhodamine and doxorubicin-HCl) and hydrophobic (i.e.…”

“…Both hydrophilic (i.e., rhodamine and doxorubicin-HCl) and hydrophobic (i.e. paclitaxel) anticancer agents have been loaded in arginine-rich peptide liposomes in order to improve the uptake of both drugs inside cancer cells [33]. …”

“…Amphiphilic peptide nanovesicles have been used for loading hydrophobic drugs in their alkyl core, while the shell is modified to improve intracellular delivery [66]. Moreover, modifications have been applied to increase targeting activity and intracellular delivery efficacy [33]. Several self-assembled peptide structures have been used for loading anticancer agents, such as doxorubicin, paclitaxel, curcumin, and fluorouracil and studied in preclinical and clinical trials, owing to their excellent biodegradability and biocompatibility.…”