ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 µg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.

Image-Guided Enhanced PDT/PTT Combination Therapy Using Brominated Hemicyanine-Loaded Folate Receptor-Targeting Ag2S Quantum Dots.

Tumor-targeting nanoparticles and phototherapies are the two major trends in tumor-specific, local cancer therapy with minimal side effects. Organic photosensitizers (PSs) usually offer effective photodynamic therapy (PDT) but require enhanced solubility and tumor-targeting, which may be provided by a nanoparticle. Near-infrared (NIR)-emitting Ag2S quantum dots may act as a delivery vehicle for the PS, NIR tracking agent, and as a phototherapy (PTT) agent. A combination of the two provides luminescent dual-phototherapy agents with tumor-specificity and image-guided and enhanced cytotoxicity as a result of synergistic PDT and PTT. In this study, brominated hemicyanine (Hemi-Br), a photosensitizer, was loaded onto folic acid (FA)-tagged, glutathione (GSH)-coated Ag2S quantum dots (AS-GSH QDs) to provide enhanced phototoxicity via a photodynamic and mild photothermal effect in folate receptor(+) cancer cell lines at clinically relevant 640 nm irradiation. Final particles (AS-GSH-FA/Hemi-Br) had a hydrodynamic size of 75.5 nm, dual emission at both 705 and 910 nm, and a 93% light-to-heat conversion efficiency under 640 nm laser irradiation. In vitro cytotoxicity studies were conducted with folate receptor (FR)-positive HeLa and -negative A549 cell lines to differentiate receptor-mediated uptake. Enhanced phototoxicity on HeLa cells was observed with AS-GSH-FA/Hemi-Br compared to free Hemi-Br and AS-GSH-FA QDs due to increased uptake of the photosensitizer via active targeting and combination therapy, which is especially visible at the safe dose of single agents. Upon irradiation with a 640 nm (300 mW, 0.78 W/cm2) laser for 5 min, the viability of the HeLa cells decreased from 64% to 42 and 25% when treated with free Hemi-Br, AS-GSH-FA, and AS-GSH-FA/Hemi-Br, respectively. Overall, AS-GSH-FA/Hemi-Br provides image-guided enhanced PDT/PTT, which may be adopted for different FR(+) tumors.

Recent Advances in Cyanine-Based Phototherapy Agents.

Phototherapies, in the form of photodynamic therapy (PDT) and photothermal therapy (PTT), are very promising treatment modalities for cancer since they provide locality and turn-on mechanism for toxicity, both of which are critical in reducing off-site toxicity. Irradiation of photosensitive agents demonstrated successful therapeutic outcomes; however, each approach has its limitations and needs to be improved for clinical success. The combination of PTT and PDT may work in a synergistic way to overcome the limitations of each method and indeed improve the treatment efficacy. The development of single photosensitive agents capable of inducing both PDT and PTT is, therefore, extremely advantageous and highly desired. Cyanine dyes are shown to have such potential, hence have been very popular in the recent years. Luminescence of cyanine dyes renders them as phototheranostic molecules, reporting the localization of the photosensitive agent prior to irradiation to induce phototoxicity, hence allowing image-guided phototherapy. In this review, we mainly focus on the cyanine dye-based phototherapy of different cancer cells, concentrating on the advancements achieved in the last ten years.

A Bottom-Up Approach for Developing Aptasensors for Abused Drugs: Biosensors in Forensics.

Aptamer-based point-of-care (POC) diagnostics platforms may be of substantial benefit in forensic analysis as they provide rapid, sensitive, user-friendly, and selective analysis tools for detection. Aptasensors have not yet been adapted commercially. However, the significance of the applications of aptasensors in the literature exceeded their potential. Herein, in this review, a bottom-up approach is followed to describe the aptasensor development and application procedure, starting from the synthesis of the corresponding aptamer sequence for the selected analyte to creating a smart surface for the sensitive detection of the molecule of interest. Optical and electrochemical biosensing platforms, which are designed with aptamers as recognition molecules, detecting abused drugs are critically reviewed, and existing and possible applications of different designs are discussed. Several potential disciplines in which aptamer-based biosensing technology can be of greatest value, including forensic drug analysis and biological evidence, are then highlighted to encourage researchers to focus on developing aptasensors in these specific areas.