Novel PEGylated Nanoassemblies Made of Self‐Assembled Squalenoyl Nucleoside Analogues

Abstract

This study describes a new simple method to obtain high loading of anticancer or antiviral nucleoside analogues into “stealth” poly(ethylene glycol) (PEG)‐coated nanoassemblies. These nanodevices are obtained by co‐nanoprecipitation in water of (i) squalenoyl prodrugs obtained by the bioconjugation of the natural lipid squalene with either the anticancer drug gemcitabine (Gem‐Sq) or the antiviral drug deoxycytidine (ddC‐Sq) with (ii) a PEG derivative of either cholesterol (Chol‐PEG) or squalene (Sq‐PEG). It was found that both PEG derivatives (Chol‐PEG or Sq‐PEG) were efficiently incorporated in the resulting composite nanoassemblies (CNAs), as shown by radioactivity studies, Zeta potential determination, and size measurements. Optimal compositions were defined for each PEG derivative to ensure the best stability in water and in buffer solutions. X‐ray diffraction and electron microscopy investigations revealed that depending on the structure of the squalenoyl nucleoside analogue used (Gem‐Sq or ddC‐Sq), these nanoassemblies might be toroids or cubosomes. Following PEGylation, the Gem‐Sq nanoassemblies displayed superior in vitro anticancer activity on gemcitabine‐resistant leukemia L1210 10K cells than either their non‐PEGylated counterparts or gemcitabine alone.

Brown Algae (Phaeophyceae) from the Coast of Madagascar: preliminary Bioactivity Studies and Isolation of Natural Products

“…The data obtained from 1D and 2D NMR experiments unambiguously led to the elucidation of compound 1 as (4 E ,8 E ,12 E ,16 E )-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-ol, which is also known as 1,1′,2-trinorsqualenol, with full assignment of all 1 H and 13 C NMR signals. Our 1 H and 13 C NMR data are in good agreement with those of the synthetic product described by Gref and coworkers [ 15 ] whereas the original data of Prestwich et al [ 16 ] deviate slightly (Tables 1 , 2 ).…”

“…Our 1 H and 13 C NMR data are in good agreement with those of the synthetic product described by Gref and coworkers [ 15 ] whereas the original data of Prestwich et al [ 16 ] deviate slightly (Tables 1 , 2 ).…”

Self-Assembly of Squalene-Based Nucleolipids: Relating the Chemical Structure of the Bioconjugates to the Architecture of the Nanoparticles

“…The wedge shape of deoxycytidine-Sq ( p ≈ 1.07) is anticipated to be less pronounced than that of ddC-Sq ( p ≈ 1.26) because its molecular area is slightly larger. This should result in decreased spontaneous monolayer curvature, inducing an enlargement of the unit cell size of the Pn 3 m phase that is consistent with the increase in the measured lattice parameter from 77.2 Å in ddC-Sq to 102.7 Å in deoxycytidine-Sq. The difference in spontaneous monolayer curvature of ddC-Sq and deoxycytidine-Sq could also explain the coexistence of the Pn 3 m (D) and Ia 3 d (G) phases in ddC-Sq samples whereas only the Pn 3 m phase was observed in deoxycytidine-Sq.…”

PEGylated squalenoyl-gemcitabine nanoparticles for the treatment of glioblastoma

“…1A). As previously described, increasing the amount of SQ-PEG in the formulation decreased the diameter of the particles, likely due to a reduced surface tension between the aqueous phase and the organic phase [38]. The addition of SQ-PEG also decreased the surface charge of the nanoparticles, rendering them nearly neutral (Fig.1B).…”