科研之友
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摘要
alpha-Tocopheryl succinate (alpha-TOS) is a well-known mitochondrially targeted anticancer compound. However, a major factor limiting the use of alpha-TOS is its low solubility in physiological media. To overcome this problem, the aim of this work is the preparation of new polymeric and active alpha-TOS-based nanovehicle with a precise control over its macromolecular architecture. Reversible addition-fragmentation chain transfer polymerization (RAFT) is used to synthesize an alpha-TOS amphiphilic block copolymer with highly homogeneous molecular weight and relatively narrow dispersity. Macro-chain transfer agents (macro-CTA) based on poly(ethylene glycol) (PEG) of different molecular weights (MW, ranging from 4.6 to 20 kDa) are used to obtain block copolymers with different hydrophilic/hydrophobic ratios with PEG being the hydrophilic block and a methacrylic derivative of alpha-tocopheryl succinate (MTOS) being the monomer that formed the hydrophobic block. PEG-b-poly (MTOS) form spherical nanoparticles (NPs) by self-organized precipitation (SORP) or solvent exchange in aqueous media enabling to encapsulate and deliver hydrophobic molecules in their core. The resulting NPs are rapidly endocytosed by cancer cells. The biological activity of the synthesized NPs are found to depend on the MW of PEG, with the NP comprised of the higher MW copolymer resulting in a lower bioactivity due to PEG shielding, inhibiting cellular uptake by endocytosis. Moreover, the biological activity also depends on the MTOS content, as the biological activity increases as a function of MTOS concentration.
- 出版日期2016
