Abstract
Disassemblable micelles for intracellular delivery of doxorubicin were developed based on a reduction-degradable amphiphilic polyamide amine- g-polyethylene glycol graft copolymer containing disulfide linkages throughout the main chain. The micelles are spherical of less than 50 nm in diameter, and can load doxorubicin in the core with drug loading content up to 20%. The micelles are stable in normal physiological condition, and quickly disassemble in reductive condition due to the cleavage of the disulfide linkages. The drug release of the micelles in normal condition is less than 25% within 24 h, whereas in the presence of reductive agent, DTT, the micelles can quickly release the entire loaded drug within 10 h. CLSM observation showed that the micelles can effectively deliver the drug cargo into nuclei after internalized through endocytosis. Cytotoxicity of the drug-loaded disassemblable micelles was demonstrated using human cervical cancer cell line (HeLa) and human liver carcinoma cell line (HepG2).
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