A Phytochemical-Based Copolymer Derived from Coriolus versicolor Polysaccharopeptides for Gene Delivery

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Coriolus versicolor is an herb widely used for cancer treatment in traditional Chinese medicine. Its active ingredients, polysaccharopeptides (PSP), have been used for adjuvant therapies in cancer treatment. This study conjugates Coriolus versicolor PSP with poly(ethylenimine) (PEI) to generate a PSP-PEI copolymer for gene transfer. After PEI conjugation, both the pH buffering capacity and DNA compaction ability of PSP are significantly increased. Compared with that of PSP, the transfection efficiency of PSP-PEI is 10 to 20-fold higher in vitro. This is a proof-of-concept study reporting the direct use of bioactive phytochemicals from traditional Chinese medicine for gene vector development. The promising performance of PSP-PEI raises the possibility that bioactive herbal ingredients can be further developed as a multi-therapeutic gene carrier for tackling cancers.

C. versicolor PSP are water-soluble substances having a dark brown colour and characteristic odour. Their polysaccharide moieties are highly complex, consisting of glucose molecules linked with different sugar units (e.g., galactose, mannose, arabinose, and xylose); whereas the peptide moieties contain a large amount of aspartic acid and glutamic acid, with acidic and neutral amino acids (such as leucine, glycine, alanine, threonine, serine, glutamic acid, valine and aspartic acid) accounting for 70% of all kinds of amino acids present. PEI is a cationic aziridine polymer that exists as a polycation showing high pH buffering capacity over a broad range of pH values. Previous studies have revealed that the transfection efficiency and cytotoxicity of PEI are positively related to the molecular weight of PEI. As the aim of PEI incorporation in this study is to enhance the positive charge density of PSP, LMW PEI (e.g., PEI 0.8K) is adopted because it can serve the purpose and is less toxic than its high-molecular-weight counterparts. During synthesis, 1,1′-carbonyldiimidazole (CDI), which activates the hydroxyl groups of PSP to form active imidazolyl carbamate intermediates, is used as a coupling agent. The intermediates are subsequently attacked by the primary amine groups of PEI to form PSP-PEI, with imidazole being released as a byproduct. (Molecules. 2018 Sep 6;23(9):2273.)

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