A multifunctional theranostic platform based on phthalocyanine-loaded dendrimer for image-guided drug delivery and photodynamic therapy.

Owing to the outstanding near-infrared (NIR) optical properties, phthalocyanines (Pc) have promising potential as theranostic agents for fluorescence image-guided drug delivery and noninvasive treatment of deep tumors by photodynamic therapy (PDT). Nevertheless, clinical application of phthalocyanines is substantially limited by poor water solubility, aggregation and insufficient selectivity for cancer cells. To address these issues, we have developed a novel dendrimer-based theranostic platform for tumor-targeted delivery of phthalocyanines. The preparation procedure involved the modification of the Pc molecule with a hydrophobic linker, which significantly enhances physical encapsulation of the hydrophobic drug into a generation 4 polypropylenimine (PPI G4) dendrimer. In order to improve biocompatibility and tumor-targeted delivery, the surface of the resulting Pc-PPIG4 complexes was additionally modified with poly(ethylene glycol) (PEG) and luteinizing hormone-releasing hormone (LHRH) peptide, respectively. The developed nanocarriers have an average diameter of 62.3 nm and narrow size distribution with a polydispersity index of 0.100. The drug encapsulation efficiency was 20% w/w, and the synthesized phthalocyanine derivative entrapped in the dendrimer-based nanocarrier exhibits a distinct NIR absorption (700 nm) and fluorescence emission (710 and 815 nm), required for an efficient PDT and fluorescence imaging. It was demonstrated that subcellular localization in vitro and organ distribution in vivo of the developed nanocarrier can be determined based on the intrinsic fluorescence properties of encapsulated phthalocyanine, validating its role as an imaging agent. The imaging experiments revealed that the LHRH targeted nanocarrier is capable of an efficient internalization into cancer cells as well as tumor accumulation when intravenously administered into mice. Finally, the prepared formulation exhibited low dark cytotoxicity (IC50=28 μg/mL) while light irradiation of the cancer cells transfected with the developed theranostic agents resulted in significant PDT effects (IC50=0.9 μg/mL) through excessive generation of toxic reactive oxygen species. Thus, the obtained results demonstrated significant potential of the designed dendrimer-based nanocarrier as an efficient NIR theranostic agent.