Journal of Innovative Optical Health Sciences

Promising biomedical applications of hybrid materials composed of gold nanoparticles and nucleic acids have attracted strong interest from the nanobiotechnological community. The particular interest is owing to the robust and easy-to-make synthetic approaches, to the versatile optical and catalytic properties of gold nanoparticles combined with the molecular recognition and programmable properties of nucleic acids. The significant progress is made in the development of DNA–gold nanostructures and their applications, such as molecular recognition, cell and tissue bioimaging, targeted delivery of therapeutic agents, etc. This review is focused on the critical discussion of the recent applications of the gold nanoparticles–nucleic acids hybrids. The effect of particle size, surface, charge and thermal properties on the interactions with functional nucleic acids is discussed. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Emphasis is placed on the systematization of data over the theranostic systems on the basis of the gold nanoparticles–nucleic acids hybrids. Specifically, we start our discussion with observation of the recent data on interaction of various gold nanoparticles with nucleic acids. Further we describe existing gene delivery systems, nucleic acids detection, and bioimaging technologies. Finally, we describe the phenomenon of the polymerase chain reaction improvement by gold nanoparticle additives and its potential underlying mechanisms. Lastly, we provide a short summary of reported data and outline the challenges and perspectives.

The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application. The micro-scale spatially offset Raman spectroscopy (micro-SORS) with an optical fiber probe, colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns, shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restriction, particularly with the combination of surface-enhanced Raman spectroscopy (SERS). However, a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking. Herein, we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared (NIR) region using a portable Raman spectrometer with a micro-SORS probe (2.1mm in diameter) and a conventional hand-held probe (9.7mm in diameter). Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant (4-nitrobenzenethiol) or resonant Raman reporter molecules (IR-780 iodide). The SERS measurements show that the penetration depths of two Raman nanotags are both over 2cm in agarose gel and 3mm in porcine muscle. The depth could be improved to over 4cm in agarose gel and 5mm in porcine tissue when using the micro-SORS system. This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue, offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.

With the increase in mortality caused by pathogens worldwide and the subsequent serious drug resistance owing to the abuse of antibiotics, there is an urgent need to develop versatile analytical techniques to address this public issue. Vibrational spectroscopy, such as infrared (IR) or Raman spectroscopy, is a rapid, noninvasive, nondestructive, real-time, low-cost, and user-friendly technique that has recently gained considerable attention. In particular, surface-enhanced Raman spectroscopy (SERS) can provide a highly sensitive readout for bio-detection with ultralow or even trace content. Nevertheless, extra attachment cost, nonaqueous acquisition, and low reproducibility require the conventional SERS (C-SERS) to further optimize the conditions. The emergence of dynamic SERS (D-SERS) sheds light on C-SERS because of the dispensable substrate design, superior enhancement and stability of Raman signals, and solvent protection. The powerful sensitivity enables D-SERS to perform only with a portable Raman spectrometer with moderate spatial resolution and precision. Moreover, the assistance of machine learning methods, such as principal component analysis (PCA), further broadens its research depth through data mining of the information within the spectra. Therefore, in this study, D-SERS, a portable Raman spectrometer, and PCA were used to determine the phenotypic variations of fungal cells Candida albicans (C. albicans) under the influence of different antifungals with various mechanisms, and unknown antifungals were predicted using the established PCA model. We hope that the proposed technique will become a promising candidate for finding and screening new drugs in the future.

Creatinine level in urine is an important biomarker for renal function diseases, such as renal failure, glomerulonephritis, and chronic nephritis. The Au@MIL-101(Fe) was prepared by in situ growth of Au nanoparticles in MIL-101(Fe) as a selective SERS substrate. The Au@MIL-101(Fe) offers the great local surface plasmon resonance (SPR) effect due to gold nanoparticles aggregation inside metal-organic frameworks. The framework structure could enrich trace target samples and drag them into SPR hot spots. The optimal Au@MIL-101(Fe) composite substrate is used for analyzing creatinine in urine and the limit of detection is down to 0.1$\mu$mol/L and a linear relationship is ranging from 1$\mu$mol/L to 100$\mu$mol/L.

Catalysis-based chemodynamic therapy (CDT) is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide (H₂O${}_2)$ into a toxic hydroxyl radical ($\cdot$OH). The performance of CDT is greatly dependent on PDT agent. Herein, mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer (CytcApt) as template. The obtained CytcApt-PtNCs can produce $\cdot$OH by H₂O₂ under the acidic conditions. Moreover, CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner, but had no side effect on normal 293T cells. Therefore, CytcApt-PtNCs possess excellent therapeutic effect and good biosafety, indicating their great potential for CDT.

The development of surface-enhanced Raman scattering (SERS) devices for detection of trace pesticides has attracted more and more attention. In this work, a large-area self-assembly approach assisted with reactive ion etching (RIE) is proposed for preparing SERS devices consisting of Ag-covered “hedgehog-like” nanosphere arrays (Ag/HLNAs). Such a SERS device has an enhancement factor of $2.79\times 10^7$, a limit of detection (LOD) up to 10${}^{-12}$M for Rhodamine 6G (R6G) analytes, and a relative standard deviation (RSD) smaller than 10%, demonstrating high uniformity. Besides, for pesticide detections, the device achieves an LOD of 10${}^{-8}$M for thiram molecules. It indicates that the proposed SERS device has a promising opportunity in detecting toxic organic pesticides.

Docetaxel-based chemotherapy, as the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), has succeeded in helping quite a number of patients to improve quality of life and prolong survival time. However, almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially. This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy (SERS). A total of 32 mCPRC patients who underwent docetaxel chemotherapy at our center from July 2016 to March 2018 were included in this study. Patients were dichotomized in prostate-specific antigen (PSA) response group ($n=17$) versus PSA failure group ($n=15$) according to the response to docetaxel. In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline ($q$0) and after 1 cycle of docetaxel chemotherapy ($q$1). Comparing Raman peaks of serum samples at baseline ($q$0) between two groups, significant differences revealed at the peaks of 638, 810, 890 ($p<0.05$) and 1136cm${}^{-1}$ ($p<0.01$). The prediction models of peak 1363cm${}^{-1}$ and principal component analysis and linear discriminant analysis (PCA–LDA) based on Raman data were established, respectively. The sensitivity and specificity of the prediction models were 71%, 80% and 69%, 78% through the way of leave-one-out cross-validation. According to the results of five-cross-validation, the PCA–LDA model revealed an accuracy of 0.73 and AUC of 0.83.

Surface-enhanced Raman scattering (SERS) spectroscopy is presented as a sensitive and specific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer. In order for clinical application of SERS technique, an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive, stable and highly reproducible Raman signals. In this contribution, we determined the ideal conditions for bulk synthesis of Raman reporter (Ra) molecules embedded silver-gold core-shell nanoparticles (Au@Ra@ AgNPs) using hydroquinone as reducing agent of silver nitrate. By using UV-Vis spectroscopy, Raman spectroscopy and transmission electron microscopy (TEM), we found that a 2:1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal. Through stability testing of the optimized Au@Ra@AgNPs over a two-week period, these SERS nanotags were found to be stable with minimal signal change occurred. The stability of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis, thus, we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody, in which the stability of bioconjugated SERS nanotags was tested over eight days. Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conjugated SERS nanotags, indicating the great potential of the synthesized SERS nanotags for future applications which require large, reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.