Near infra-red absorbing Quinolizidine fused curcuminoid-BF2 chelate and its applications in photodynamic therapy using MCF-7 and A549 cells

Abstract

Metal-free near-infrared absorbing photosensitizers (PS) have been considered promising candidates for photodynamic therapy. Curcumin, curcuminoid, and its derivatives have therapeutic values due to their anti-inflammatory, antifungal, and antiproliferative properties. Curcuminoid-BF₂ chelates have also been studied as cell imaging probes, however, their applications in photodynamic therapy are rare. In this article, we describe the synthesis and therapeutic evaluation of quinolizidine fused curcuminoid-BF2 chelate (Quinolizidine CUR-BF₂) containing an acid-sensitive group. This donor-acceptor-donor curcuminoid-BF2 derivative exhibits absorption and emission in the deep red region with an absorption band maximum of ∼647 nm and a weak emission band at approximately 713 nm. It is interesting to note that this derivative has a high molar extinction coefficient (164,655 M^-1cm^-1). Quinolizidine CUR-BF₂ possesses intramolecular charge transfer properties, facilitating the production of singlet oxygen (¹O₂), which plays a crucial role in cell death. Additionally, Quinolizidine CUR-BF₂ can enable the selective release of active ingredients in an acidic medium (pH 5). Furthermore, the nanoaggregates of PS were prepared by encapsulating Quinolizidine CUR-BF₂ within Pluronic F127 block co-polymer for better water-dispersibility and enhanced cellular uptake. Dark cytotoxicity of nanoaggregates was found to be negligible, whereas they exhibited significant photoinduced cytotoxicity towards cancer cells (MCF-7 and A549) under irradiation of 635 nm light. Further, the cell death pathway using Quinolizidine CUR-BF₂ nanoaggregates as PS is found to occur through apoptosis. Specifically, the present study deals with the successful preparation of Quinolizidine CUR-BF₂ nanoaggregates for enhanced water-dispersibility and cellular uptake as well as the efficacy evaluation of developed nanoaggregates for photodynamic therapy.

Keywords: Curcuminoid-BF(2); Cytotoxicity; Photodynamic therapy; Singlet oxygen; apoptosis.