Smart delivery system of photosensitizer chlorin e6 (Ce6) has been developed for targeted photodynamic therapy (PDT). Simple self-assemblies of the mixtures comprising soybean lecithin derived phosphatidylcholine (PC), phosphatidylethanolamine-poly(L-histidine)40 (PE-p(His)40), and folic acid (FA) conjugated phosphatidylethanolamine-poly(N-isopropylacrylamide)40 (PE-p(NIPAM)40-FA) in different ratios yield smart nanospheres characterized by (i) stable and uniform particle size (∼100 nm), (ii) positive surface charge, (iii) high hydrophobic drug (Ce6) loading efficiency up to 45%, (iv) covalently linked targeting moiety, (v) low cytotoxicity, and (vi) smartness showing p(His) block oriented pH and p(NIPAM) oriented temperature responsiveness. The Ce6-encapsulated vesicular nanospheres (Ce6@VNS) were used to confirm the efficiency of cellular uptake, intracellular distribution, and phototoxicity against KB tumor cells compared to free Ce6 at different temperature and pH conditions. The Ce6@VNS system showed significant photodynamic therapeutic efficiency on KB cells than free Ce6. A receptor-mediated inhibition study proved the site-specific delivery of Ce6 in targeted tumor cells.
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