Solution Self-Assemblies of Sequence-Defined Ionic Peptoid Block Copolymers

A series of amphiphilic ionic peptoid block copolymers where the total number (1 or 3) and position of ionic monomers along the polymer chain are precisely controlled have been synthesized by the submonomer method. Upon dissolution in water at pH = 9, the amphiphilic peptoids self-assemble into small spherical micelles having hydrodynamic radius in ∼5–10 nm range and critical micellar concentration (CMC) in the 0.034–0.094 mg/mL range. Small-angle neutron scattering (SANS) analysis of the micellar solutions revealed unprecedented dependence of the micellar structure on the number and position of ionic monomers along the chain. It was found that the micellar aggregation number (<i>N</i>_agg) and the micellar radius (<i>R</i>_m) both increase as the ionic monomer is positioned progressively away from the junction of the hydrophilic and hydrophobic segments along the polymer chain. By defining an ionic monomer position number (<i>n</i>) as the number of monomers between the junction and the ionic monomer, <i>N</i>_agg exhibited a power law dependence on <i>n</i> with an exponent of ∼1/3 and ∼3/10 for the respective singly and triply charged series. By contrast, <i>R</i>_m exhibited a weaker dependence on the ionic monomer position by a power law relationship with an exponent of ∼1/10 and ∼1/20 for the respective singly and triply charged series. Furthermore, <i>R</i>_m was found to scale with <i>N</i>_agg in a power-law relationship with an exponent of 0.32 for the singly charged series, consistent with a weakly charged ionic star-like polymer model in the unscreened regime. This study demonstrated a unique method to precisely tailor the structure of small spherical micelles based on ionic block copolymers by controlling the sequence and position of the ionic monomer

The Combined Effect of Encapsulating Curcumin and C6 Ceramide in Liposomal Nanoparticles against Osteosarcoma

This study examines the antitumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared: curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed primary human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G₂/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G₁ arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G₂/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested <i>in vivo</i> using a human osteosarcoma xenograft assay. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery <i>in vivo</i>, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy