Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting.

tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (p < 0.001) increase in AUCINF_obs and a 1.4-fold decrease (p < 0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by in vivo imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice.

Investigations on the influence of the structural flexibility of nanoliposomes on their properties.

In the present study, nanoliposomes with tuneable structure elasticity were prepared by reverse-phase evaporation. Both Fluorescence Polarization and Fluorescence Resonance Energy Transfer was employed to characterize the structural elasticity of resultant nanoliposomes. Temozolomide, a kind of hydrophilic drug as the first-line treatment choice for glioblastoma, was encapsulated into nanoliposomes. The results showed that the flexibility of nanoliposomes gradually increased with sodium cholate, while decreasing with cholesterol, Labrafac CC and Labrafac PG adding. Furthermore, the structural flexibility of nanoliposomes was positively correlated with the encapsulation efficiency and release rate and cellular uptake. Our research reveals the structural flexibility of nanoliposomes could affect in vitro characteristics and thereafter in vivo behaviors of nanoliposomes.