Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Abstract

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21 H ,23 H -porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments

“…A nanocontruct approach was applied by Rao et al 47 who synthesized a dual functional dendrimer poly(amidoamine) (PAMAM) for targeted drug delivery to tumor tissues. The carboxyl functionalized dendrimer was conjugated with a nitrilotriacetic (NTA) group, Ni 2+ and near‐infrared (NIR) sensitive 5,10,15,20‐tetrakis(4‐hydroxyphenyl)‐21H,23H‐porphine (2H‐OHTPP).…”

Nanotherapeutic Intervention in Photodynamic Therapy for Cancer

“…; second, the dendrimer and PS are bonded covalently; third, PS serves as a frame for the development of a dendrimer. 137 Narsireddy et al 138 attached nitrile tri acetic acid (NTA) group and 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine (PS) in a dendrimer, which is the second method for conjugating PS with a dendrimer. They linked a peptide that was unique to human epidermal growth factor 2 to the NTA group on the dendrimer so that it could work as a tumor-targeting peptide for customized in vitro and in vivo PDT.…”

Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment

“…Metallic and polymer-based nanocarrier delivery systems have garnered considerable attention as anti-cancer drug carriers 22–24 . Among those drug delivery systems, poly (amidoamine) (PAMAM) dendrimers has advantages, such as the availability of numerous free amino groups that can be functionalized with multiple biomolecules and the ability to incorporate hydrophilic and/or hydrophobic drugs 25–27 . Moreover, dendrimers functionalized with targeting ligands can effectively deliver chemotherapeutics and siRNA specifically into tumor tissues 28,29 .…”