Exploration of interfacial dynamics in squaraine based nanohybrids for potential photodynamic action
Graphical abstract
Interfacial Dynamics in Nanohybrid with Targeted Photo-toxicity.
Introduction
Squaraine, condensation products of electron-rich substrates and squaric acid derivatives, with a four-membered squaraine ring present into the polymethine chain structure consist of absorption maxima in longer wavelength region [[1], [2], [3]]. Besides large applications in dye sensitized solar cell [4], squaraine dyes impose greater light-absorption ability at low-energy region and higher photo-stability with respect to other available commercial dye and can be considered as photomedicine [5]. Recently, photodynamic therapy (PDT) substantiates its effectivity towards destruction of malignancy in a minimally invasive approach [6]. PDT involves a photosensitizer (PS) molecule that can be excited from the ground state to excited state upon irradiation of light of specific wavelength similar to the band-energy gap of the molecule [7], producing active molecular species, such as free radicals and reactive oxygen species (ROS) following cell death [8]. The efficacy of PDT depends on several factors as light and drug dosimetry, drug localization to the diseased site, light exposure and its penetration capability through biological tissues [9,10]. In this view, SQ can be considered as a new age photosensitizer molecule [11]. However, low water solubility and aggregation in biological fluid restrict their applications [12]. The aggregated forms include deactivation of excited state through various non-radiative process which lowers the ROS generation capability [13]. Thus, several drug delivery agents are employed to enhance the effectivity of squaraine.
Earlier it was reported that chitosan, a biopolymer based drug-delivery system with hydrophilicity, biocompatibility, biodegradability properties can serve well as a platform for squaraine delivery [14]. The incorporation of dyes onto suitable surfaces improve molecular rigidification by diminishing the photoisomerization process which enhance dye photostability and solubility [15]. On the other hand, inorganic nanoparticles (NPs) with wide band gap often establish themselves as a candidate for better drug loading as well as an active component for enhancing the drug activity [16]. In this purpose, ZnO NPs with a wide band gap of3.3 eV is a promising nanomaterial. ZnO itself often depicts photodynamic action in presence of UV irradiation [17] and generates ROS that can kill the cancer [18]. The pH responsive precipitation and dissolution of ZnO NPs can magnify its potential as cancer therapeutics [19]. However, UV light is itself very much harmful for human tissue often affecting the normal tissues significantly [20]. Thus, surface functionalization of ZnO NPs with photosensitizer molecules can lead to nanohybrids formation with alternate properties that will lead to a new avenue of nanoparticles based PDT systems [21,22].
Herein, we have examined a squaraine dye (SQ) with absorption at longer wavelength region for potential PDT application. The dye depicted absorbance at 665 nm and emission at 675 nm and thus can be consider as a novel PDT agent. Next, we have synthesised the surface modified ZnO NPs using the dye as the sensitizer. To check the integrity of nanohybrids formation, we have followed Fӧrster resonance energy transfer (FRET) from donor ZnO to acceptor SQ molecule. The photo-induced electron transfer process is estimated using time-resolved fluorescence decay transients. The enhanced water stability, lesser aggregation, pH responsive delivery of drug in the nanohybrids has been monitored. The ROS generation was assessed using dichlorofluorescin (DCFH) assay. We have tested and checked the light penetration efficacy through a mimic human tissue and evaluated the cytotoxicity of ZnO-SQ nanohybrids on human breast cancer cell line MCF-7. The present study depicts physico-chemical insight of an inorganic-organic hybrid material for potential biological effectivity.
Section snippets
Reagents
Analytical grade chemicals were used for synthesis without further purification. Squaraine dye (Sensidizer SQ2) was purchased from Solaronix. ZnO NPs (approximately of 30 nm size) were obtained from Sigma-Aldrich. The suitable solvent used for preparing dye solution was DMSO (Merck). Millipore water was used to make the aqueous solution. p-Benzoquinone (BQ) reagent was purchased from Alfa-Aesar. Dilute solution of phosphate buffer (pH7.4) and acetate buffer (pH∼5) were used as the medium for
Results & discussion
The chemical structure of the used Squaraine (SQ) dye is depicted in Fig. 1a. SQ shows typical visible-near IR absorption characteristics in the phototherapeutic window between 600–700 nm. The absorption maximum of SQ is at 665 nm with a shoulder peak at 610 nm in DMSO. Here, 50 μm SQ concentration was employed in DMSO solvent to check absorption feature with minimal effect of solvent dependent aggregation nature of dye. The absorbance at the red region of the spectrum arises from the
Conclusions
The present study elucidates a novel approach to improve the effectiveness of photodynamic therapy in cancer treatment using a nano-dimensional hybrid material. Herein, we have intentionally chosen squaraine as the photosensitizer molecule as it depicts optical absorption at the biologically transparent window. The optical properties and aggregation in aqueous media have been observed using steady-state absorption and fluorescence spectroscopy. Then, we have employed ZnO NPs as the inorganic
Acknowledgements
D.B. thanks the Department of Science and Technology (DST, India) for INSPIRE fellowship. We thank DST-SERB EMR/2016/004698 and DBT-BT/PR11534/NNT/28/766/ 2014 for financial support.
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