The effect of the triblock properties on the morphologies and photophysical properties of nanoparticle loaded with carboxylic dendrimer phthalocyanine

Photodynamic therapy (PDT) is an emerging alternative treatment for various cancers and age-related macular degeneration. Phthalocyanines (Pcs) and their substituted derivatives are under intensive investigation as the second generation photosensitizers. A big challenge for the application of Pcs is poor solubility and limited accumulation in the tumor tissues, which severely reduced its PDT efficacy. Nano-delivery systems such as polymeric micelles are promising tools for increasing the solubility and improving delivery efficiency of Pcs for PDT application. In this paper, nanoparticles of amphiphilic triblock copolymer poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) were developed to encapsulate 1-2 generation carboxylic poly (benzyl aryl ether) dendrimer. The morphologies and photophysical properties of polymeric nanoparticles loaded with 1-2 generation dendritic phthalocyanines (G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m) were studied by AFM, UV/Vis and fluorescent spectroscopic method. The morphologies of self-assembled PLL-PEG-PLL aggregates exhibited concentration dependence. Its morphologies changed from cocoon-like to spheral. The diameters of G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m were in the range of 33-147 nm, increasing with the increase of the concentration of PLL-PEG-PLL. The morphologies of G2-ZnPc(COOH)16/m also changed from cocoon-like to sphere with the increase of the concentration of PLL-PEG-PLL. It was found that, the no obviously Q change was observed between the free phthalocyanines and nanoparticles. The fluorescence intensity of polymer nanoparticles were higher enhanced compared with free dendritic phthalocyanines. The dendrimer phthalocyanine loaded with poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) presented suitable physical stability, improved photophysical properties suggesting it may be considered as a promising formulation for PDT.

[1]  Kazunori Kataoka,et al.  Dendrimer phthalocyanine-encapsulated polymeric micelle-mediated photochemical internalization extends the efficacy of photodynamic therapy and overcomes drug-resistance in vivo. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Petr Zimcik,et al.  Synthesis and studies on photodynamic activity of new water-soluble azaphthalocyanines , 2003 .

[3]  V. Torchilin Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[4]  Petr Zimcik,et al.  Comparison of aggregation properties and photodynamic activity of phthalocyanines and azaphthalocyanines , 2006 .

[5]  Vladimir Torchilin,et al.  Tumor delivery of macromolecular drugs based on the EPR effect. , 2011, Advanced drug delivery reviews.

[6]  Hiroshi Maeda,et al.  Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. , 2010, Bioconjugate chemistry.

[7]  Madeleine Helliwell,et al.  Clathrate formation from octaazaphthalocyanines possessing bulky phenoxyl substituents: a new cubic crystal containing solvent-filled, nanoscale voids. , 2008, Chemistry.

[8]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[9]  Thomas J. Dougherty,et al.  Basic principles of photodynamic therapy , 2001 .

[10]  R. Haag,et al.  Supramolecular drug-delivery systems based on polymeric core-shell architectures. , 2004, Angewandte Chemie.

[11]  Bum Hoon Lee,et al.  Synthesis and optical properties of push-pull type tetrapyrazinoporphyrazines , 2005 .

[12]  Malcolm E. Kenney,et al.  Dichloro(phthalocyanino)silicon , 1965 .

[13]  Andrew Beeby,et al.  The Synthesis of Arylalkyne-Substituted Tetrapyrazinoporphyrazines and an Evaluation of Their Potential as Photosensitisers for Photodynamic Therapy , 2004 .

[14]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[15]  Michael R Hamblin,et al.  Mechanisms in photodynamic therapy: part two-cellular signaling, cell metabolism and modes of cell death. , 2005, Photodiagnosis and photodynamic therapy.