Pegylation of charged polymer-photosensitiser conjugates: effects on photodynamic efficacy

Conjugates between photosensitisers (PS) and charged polymeric carriers are under investigation for photodynamic therapy of cancer and may allow targeting to certain cell types or compartments in tumours. Covalent attachment of polyethylene glycol to macromolecules (pegylation) may alter their pharmacokinetics, cell type targeting, and photophysical properties. Macrophages may take up large amounts of aggregated PS, thus lessening the selectivity for cancer cells in tumours. We investigated the effect of pegylation on the uptake and phototoxicity of poly-L-lysine chlorin(e6) conjugates with either cationic or anionic charges in two cell lines, human ovarian cancer cells and mouse macrophages. The cationic conjugate after pegylation became less aggregated, consumed less oxygen and had reduced cellular uptake. However, the phototoxicity corrected for cellular uptake increased three- to five-fold. In contrast, the anionic succinylated conjugate on pegylation became more aggregated, consumed similar amounts of oxygen, and had higher cellular uptake. The anionic conjugate showed the highest relative phototoxicity towards both the cell lines (compared to the other three conjugates) and it decreased most towards the macrophages after pegylation. Pegylation reduced the amount of oxygen consumed per chlorin(e6) molecule when photosensitised cells were illuminated. These in vitro studies suggest that pegylation alters the phototoxicity of PS conjugates depending on the effect produced on the aggregation state.