Dendrimer Generation Effects on Photodynamic Efficacy of Dendrimer Porphyrins and Dendrimer-Loaded Supramolecular Nanocarriers

Abstract

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.

Complex coacervate core micelles

“…The formation of coordination bonds between polyelectrolyte blocks and metal ions in the C3M core, has been studied by attenuated total reflectance infrared spectroscopy (ATR-FTIR) [156]. Atomic force microscopy (AFM), [15,87,106,[184][185][186]199,231,241] transmission electron microscopy (TEM), [63,68,136,138,158,166,178,184,229] and cryogenic transmission electron microscopy (cryo-TEM) [3,45,[152][153][154]181,182] have been used to visualize (the core of) C3Ms. Potentiometric titrations have been performed to study the binding equilibrium between the oppositely charged species [68].…”

“…Other oppositely charged species that have been incorporated into C3Ms are drugs, such as dendrimer porphyrin, [160][161][162][228][229][230] cisplatin, [163,164] dibucaine, [165] tetracaine, [165] procaine, [165] doxorubicin, [168] heparin, [231] miltephosine, [232] TCAN-26, [232] low molecular weight compounds other than drugs, such as ETC, [166] and pyranine, [234] Moloney leukemia virus, [233] and coordination polymers [181][182][183].…”

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

“…The in vitro PDT effect of various sized DP-loaded micelles has been tested for HeLa (human cervical adenocarcinoma) cells. 36 Micelles loaded with third-generation DPs exhibited the highest photocytotoxicity.…”

“…Using small dendrimers to form PIC micelles resulted in aggregates with a large size distribution, indicating that the relatively open architectures and small dendritic wedges may not completely prevent p-p interactions between the porphyrin cores. 36 Additionally, aggregates of small dendrimers had shorter fluorescence lifetimes and decreased oxygen depletion. Therefore, we conclude that the dendritic wedges in third-generation DPs might be sufficiently large to prevent focal photosensitizing units in the micellar core from self-quenching.…”

Can nanotechnology potentiate photodynamic therapy?

“…Kataoka ' s laboratory has prepared dendrimer PS based on both a Zn-porphyrin and on a Zn-phthalocyanine [79] . The porphyrin dendrimers were complexed with poly-l -lysine-PEG (PEG-PLL; see Figure 6E) block copolymers to form nanocarriers [80] . Interestingly, the larger the dendrimer (i.e., the higher the generation number), the smaller was the overall size of the nanocarrier.…”