A Novel Cyanine and Porphyrin Based Theranostic Nanoagent for Near-Infrared Fluorescence Imaging Guided Synergistic Phototherapy

Abstract

Design and synthesis of multifunctional organic nanoparticles (NPs) for non-invasive diagnosis and phototherapy of cancer are widely acknowledged. However, limited drug loading of NPs are major limitations for attaining synergistic effect in most of the combination therapies. Herein, a novel cyanine-porphyrin combined NPs (PGL-DiR) was fabricated in a simple and inexpensive way for the treatment of prostate cancer. A most commonly used near-infrared fluorescent (NIRF) cyanine dye, DiR was chosen as a photothermal agent to encapsulate in a porphyrin grafted lipid (PGL) (PGL-DiR) NPs of average size 156.25±31.31 nm. Unlike conventional liposomes, the self-assembled PGL morphology revealed encapsulation efficiency of DiR higher than 98%. However, as observed in vitro, DiR loading contents could trigger obvious quenching of singlet oxygen (¹O₂) by PGL thereby reducing the efficiency of PDT. Nevertheless, after successful photobleaching of DiR, as prepared PGL-DiR NP could facilitate enhanced synergistic photothermal and photodynamic (PTT-PDT) therapy both in vitro and in vivo. After intravenous administration of PGL-DiR NPs in a PC3 tumor xenograft mice, a high accumulation in tumor until 24 hrs was clearly evident via NIRF imaging. With the successive laser irradiation, these NPs effectively suppressed the tumor growth synergistically as PTT < PDT < PTT + PDT while compared to monotherapies such as PTT or PDT alone. These results demonstrated that as prepared PGL-NPs could serve as an excellent theranostic agent both in vitro and in vivo for combined therapy of prostate cancer.