Superior Photophysical and Photosensitizing Properties of Nanoaggregates of Weakly Emissive Dyes for Use in Bioimaging and Photodynamic Therapy

• Published in: Biomacromolecules Vol. 24; no. 11; pp. 5438 - 5450
• Main Authors: Dar, Arif Hassan, Ahmad, Anas, Kumar, Ajay, Gowri, Vijayendran, Jori, Chandrashekhar, Sartaliya, Shaifali, K. M, Neethu, Ali, Nemat, Bishnoi, Mahendra, Khan, Rehan, Jayamurugan, Govindasamy
• Format: Journal Article
• Language: English
• Published: American Chemical Society 13-11-2023
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.3c00892

The development of luminescent dyes based on 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) is an active research area, and a quantum yield (ΦF) of 7.8% has been achieved so far in cyclohexane by appending a fluorophore. Our novel method radically refines weakly emissive 2,3-disubstituted TCBD (phenyl-TCBD 1) (ΦF = 2.3% in CH3CN) into a water-soluble, biocompatible nanoformulation as highly emissive aggregates 1NPs ⊂ PF-127 with ΦF = 7.9% in H2O and without fluorophore conjugation. Characterization of 1NPs ⊂ PF-127 was carried out using various spectroscopic techniques, and its predominant size was found to be 80–100 nm according to transmission electron microscopy and dynamic light scattering techniques. Spectroscopic studies including Fourier transform infrared spectroscopy revealed that aggregated phenyl-TCBD particles were encapsulated in a nonluminescent triblock copolymer (PF-127)-based nanomicelles with the TCBD entrapment efficiency of 77%. With increasing water fraction, the phenyl-TCBD nanoaggregates exhibited a 3-fold higher quantum yield, a greater lifetime, and a red shift (155 nm). This remarkable enhancement in red emissivity enabled them to be used as a bioprobe for bioimaging applications and in photodynamic therapy to selectively target cancer cell lines with singlet oxygen generation capability (ΦΔ = 0.25). According to the MTT assay, compared to the native molecular form (1229 nM), the aggregated 1NPs ⊂ PF-127 (13.51 nM) exhibited dose-dependent cell death when exposed to light with 91-fold increased activity. The histoarchitectures of various vital organs (liver, kidneys, heart, lungs, and spleen) were intact when tested for in vivo biocompatibility. This study has significant implications for developing nonplanar push–pull chromophore-based dyes as biosensors and with potential applications beyond bioimaging.