Dendrimer generation effects on photodynamic efficacy of dendrimer porphyrins and dendrimer-loaded supramolecular nanocarriers

A series of poly(benzyl ether) dendrimer porphyrins (DPs) (Gn = n-generation dendrimer, n = 1-3) was examined as potential photosensitizers for photodynamic therapy (PDT). Polyion complexes (PICs) between the DPs and poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) were formed via an electrostatic interaction between the positively charged poly(L-lysine) (PLL) segment and negatively charged periphery of the DPs. Dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) showed that G3 formed a core-shell-type nanocarrier micelle, whereas G1 and G2 formed irregular-shaped nanoparticles with a relatively high polydispersity. The photophysical properties of the DP-loaded PIC nanocarriers strongly depend on the generation of the DPs. In the case of G1 and G2, their fluorescence lifetime and oxygen consumption ability were significantly reduced by the formation of the PIC nanocarriers, whereas the G3-loaded PIC nanocarrier exhibited almost comparable fluorescence lifetimes and oxygen consumption abilities to the free G3. The incorporation of DPs into PIC nanocarriers resulted in an appreciable increase in the cellular uptake, yet inversely correlated with the generation. Alternatively, the photocytotoxicity of the DPs within the nanocarriers increased with an increase in the generation despite a decrease in the cellular uptake. By correlating the effects of the uptake amount with the photocytotoxicity, the PIC nanocarriers showed remarkable enhancement of the PDT efficacy dependent on the generation of DPs.