Target-induced hot spot construction for sensitive and selective surface-enhanced Raman scattering detection of matrix metalloproteinase MMP-9.

Studies have found that matrix metalloproteinase-9 (MMP-9) plays a significant role in cancer cell invasion, metastasis, and tumor growth. But it is a challenge to go for highly sensitive and selective detection and targeting of MMP-9 due to the similar structure and function of the MMP proteins family. Herein, a novel surface-enhanced Raman scattering (SERS) sensing strategy was developed based on the aptamer-induced SERS "hot spot" formation for the extremely sensitive and selective determination of MMP-9. To develop the nanosensor, one group of gold nanospheres was modified with MMP-9 aptamer and its complementary strand DNA1, while DNA2 (complementary to DNA1) and the probe molecule 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) were grafted on the surface of the other group of gold nanospheres. In the absence of MMP-9, DTNB located on the 13-nm gold nanospheres has only generated a very weak SERS signal. However, when MMP-9 is present, the aptamer preferentially binds to the MMP-9 to construct MMP-9-aptamer complex. The bare DNA1 can recognize and bind to DNA2, which causes them to move in close proximity and create a SERS hot spot effect. Due to this action, the SERS signal of DTNB located at the nanoparticle gap is greatly enhanced, achieving highly sensitive detection of MMP-9. Since the hot spot effect is caused by the aptamer that specifically recognizes MMP-9, the approach exhibits excellent selectivity for MMP-9 detection. Based on the benefits of both high sensitivity and excellent selectivity, this method was used to distinguish the difference in MMP-9 levels between normal and cancer cells as well as the expression of MMP-9 from cancer cells with different degrees of metastasis. In addition, this strategy can accurately reflect the dynamic changes in intracellular MMP-9 levels, stimulated by the MMP-9 activator and inhibitor. This strategy is expected to be transformed into a new technique for diagnosis of specific cancers related to MMP-9 and assessing the extent of cancer occurrence, development and metastasis.

Clickable Polymer Ligand-Functionalized Iron Oxide Nanocubes: A Promising Nanoplatform for 'Local Hot Spots' Magnetically Triggered Drug Release.

Exploiting the local heat on the surface of magnetic nanoparticles (MNPs) upon exposure to an alternating magnetic field (AMF) to cleave thermal labile bonds represents an interesting approach in the context of remotely triggered drug delivery. Here, taking advantages of a simple and scalable two-step ligand exchange reaction, we have prepared iron oxide nanocubes (IONCs) functionalized with a novel multifunctional polymer ligand having multiple catechol moieties, furfuryl pendants, and polyethylene glycol (PEG) side chains. Catechol groups ensure a strong binding of the polymer ligands to the IONCs surface, while the PEG chains provide good colloidal stability to the polymer-coated IONCs. More importantly, furfuryl pendants on the polymer enable to click the molecules of interest (either maleimide-fluorescein or maleimide-doxorubicin) via a thermal labile Diels-Alder adduct. The resulting IONCs functionalized with a fluorescein/doxorubicin-conjugated polymer ligand exhibit good colloidal stability in buffer saline and serum solution along with outstanding heating performance in aqueous solution or even in viscous media (81% glycerol/water) when exposed to the AMF of clinical use. The release of conjugated bioactive molecules such as fluorescein and doxorubicin could be boosted by applying AMF conditions of clinical use (16 kAm-1 and 110 kHz). It is remarkable that the magnetic hyperthermia-mediated release of the dye/drug falls in the concentration range 1.0-5.0 µM at an IONCs dose as low as 0.5 gFe/L and at no macroscopical temperature change. This local release effect makes this magnetic nanoplatform a potential tool for drug delivery with remote magnetic hyperthermia actuation and with a dose-independent action of MNPs.

A surface-enhanced Raman scattering aptasensor for Escherichia coli detection based on high-performance 3D substrate and hot spot effect.

A surface-enhanced Raman scattering (SERS) aptasensor was established for highly sensitive and selective detection of Escherichia coli (E. coli). Chitosan hydrogel modified with E. coli aptamer (Apt) functionalized silver nanoparticles was constructed as a SERS 3D substrate for specific bacteria enrichment, while the Raman signaling molecule 4-mercaptobenzoic acid and E. coli Apt modified gold nanostars were prepared for the sensitive quantification of E. coli. The aptasensor exhibits intense electromagnetic field enhancement in multiple hot spot regions, including the spikes and the gap between adjacent nanostars and that between gold nanostars and silver nanoparticles. Due to the hot spot effect coupled with the selective recognition ability, a detection limit of 3.46 CFU/mL with a wide dynamic linearized range from 3.2 × 101 to 3.2 × 107 CFU/mL could be achieved without other non-target bacteria interference. Moreover, this SERS aptasensor was applied to detect E. coli in actual samples with a good recovery rate (>90%). Therefore, the developed SERS aptasensor paves a new avenue for the detection in the field of food safety and environmental pollution by replacing the corresponding aptamers.

Plant Biomarker Recognition by Molecular Imprinting Based Localized Surface Plasmon Resonance Sensor Array: Performance Improvement by Enhanced Hotspot of Au Nanostructure.

Detection of plant volatile organic compounds (VOCs) enables monitoring of pests and diseases in agriculture. We previously revealed that a localized surface plasmon resonance (LSPR) sensor coated with a molecularly imprinted sol-gel (MISG) can be used for cis-jasmone vapor detection. Although the selectivity of the LSPR sensor was enhanced by the MISG coating, its sensitivity was decreased. Here, gold nanoparticles (AuNPs) were doped in the MISG to enhance the sensitivity of the LSPR sensor through hot spot generation. The size and amount of AuNPs added to the MISG were investigated and optimized. The sensor coated with the MISG containing 20 µL of 30 nm AuNPs exhibited higher sensitivity than that of the sensors coated with other films. Furthermore, an optical multichannel sensor platform containing different channels that were bare and coated with four types of MISGs was developed to detect plant VOCs in single and binary mixtures. Linear discriminant analysis, k-nearest neighbor (KNN), and naïve Bayes classifier approaches were used to establish plant VOC identification models. The results indicated that the KNN model had good potential to identify plant VOCs quickly and efficiently (96.03%). This study demonstrated that an LSPR sensor array coated with a AuNP-embedded MISG combined with a pattern recognition approach can be used for plant VOC detection and identification. This research is expected to provide useful technologies for agricultural applications.