Helicene-Hydrazide Encapsulated Ethyl Cellulose as a Potential Fluorescence Sensor for Highly Specific Detection of Nonanal in Aqueous Solutions and a Proof-of-Concept Clinical Study in Lung Fluid

Abstract

Over the past years, lung cancer has been one of the vital cancer-related mortalities worldwide and has inevitably exhibited the highest death rate with the subsequent need for facile and convenient diagnosis approaches to identify the severity of cancer. Previous research has reported long-chain aldehyde compounds such as hexanal, heptanal, octanal, and nonanal as potential biomarkers of lung cancer. Herein, the helicene dyeencapsulated ethyl cellulose (EC@dye-NH) nanosensors have been applied for the potentially sensitive and specific detection of longchain aldehydes in aqueous media. The sensors contain the intrinsic hydrazide group of dye-NH, which is capable of reacting an aldehyde group via imine formation and the EC backbone. This offers the synergistic forces of hydrophobic interactions with alkyl long-chain aldehydes, which could induce self-assembly encapsulation of EC@dye-NH nanosensors and strong fluorescence responses. The addition of long-chain aldehyde would induce the complete micellar-like nanoparticle formation within 15 min in acetate buffer pH 5.0. The limit of detection (LOD) values of EC@dye-NH nanosensors toward heptanal, octanal, and nonanal were 40, 100, and 10 μM, respectively, without interference from the lung fluid matrices and short-chain aldehydes. For practical applicability, this sensing platform was developed for quantification of the long-chain aldehydes in lung fluid samples with 98−101% recoveries. This EC@ dye-NH nanosensor was applied to quantify nonanal contents in lung fluid samples. The results of this method based on EC@dye-NH nanosensors were then validated using standard gas chromatography−mass spectrometry (GC-MS), which gave results consistent with the proposed method. With intracellular imaging application, the EC@dye-NH nanosensors demonstrated excellent intracellular uptake and strong green fluorescence emission upon introducing the nonanal into the lung cancer cells (A549). Thus, the developed nanosensing approach served as the potential fluorescent probes in medical and biological fields, especially for lung cancer disease diagnosis based on highly selective and sensitive detection of long-chain aldehydes.

A fluorescence-based sweat test sensor in a proof-of-concept clinical study for COVID-19 screening diagnosis

“…3. In a previous work 38 regarding the fluorescent sensor (EC@dyeNH), the quantitative analysis of this sensing platform towards nonanal detection demonstrated the limit of detection at 8.40 nM and limit of quantification at 27.99 nM in the linear range of 60-110 µM (as shown in Fig. S1 †).…”

“…With the optimum intensity threshold of 73, the sensing approach offered 0.99 AUC and the accuracy, sensitivity, and specificity of 94%, 96% and 93%, respectively. It should be noted that false positive results may be observed via some other non-Covid-19 diseases, such as lung cancer with nonanal as a potential marker in lung fluid, 38 as well as other uninvestigated diseases. Due to the close contact between the skin microbiome and that along the respiratory tract, 41 nonanal may be found in the sweat of patients with lung cancer.…”

“…Particularly interesting in this regard is the development of fluorescent materials used in aqueous solutions. In our previous work, 38 nanomaterials for nonanal sensors were proudly constructed. A nonanal nanosensor based on helicene-hydrazide encapsulated in ethyl cellulose ( EC@dyeNH ) was studied.…”

Supramolecular self-assembled polymeric nanospheres based on hydrazino naphthalimide functionalised pillar[5]arene for long chain aldehyde detection

“…4,5 Recently, our group reported a novel micellar fluorescent nanoprobe based on a helicene-hydrazide motif. 6 Specific chemical reactions between aldehyde and hydrazide within the hydrophobic pocket of the ethyl cellulose matrix resulted in enhanced fluorescence emission signal in the presence of the C9 guest selectively. However, seeking new methodologies to achieve selective sensing of other long-chain aldehydes is still an important research theme nowadays.…”

Fluorescent hydrazine-naphthalimide encapsulated by ethyl cellulose for detection of long-chain aldehydes

“…Utilising the anti-solvent particle induction approach, EC@Naph nanosensors were created in this study as described in the literature 85 . To prepare a stock solution of polymeric nanosensors, 2 mg/mL of Naphthalimide dyes (Naph) and 1 mg/mL of ethyl cellulose (EC) were separately dissolved in acetone.…”