Near-Infrared-Activated Fluorescence Resonance Energy Transfer-Based Nanocomposite to Sense MMP2-Overexpressing Oral Cancer Cells

Abstract

The matrix metalloproteinases (MMPs) are well-known mediators that are activated in tumor progression. MMP2 is a kind of gelatinase in extracellular matrix remodeling and cancer metastasis processes. MMP2 secretion increased in many types of cancer diseases, and its abnormal expression is associated with a poor prognosis. We fabricated a nanocomposite that sensed MMP2 expression by a red and blue light change. This nanocomposite consisted of an upconversion nanoparticle (UCNP), MMP2-sensitive peptide, and CuInS2/ZnS quantum dot (CIS/ZnS QD). An UCNP is composed of NaYF4:Tm/Yb@NaYF4:Nd/Yb, which has multiple emissions at UV/blue-visible wavelengths under 808 nm laser excitation. The conjugated CIS/ZnS QD showed the red-visible fluorescence though the FRET process. The two fluorophores were connected by a MMP2-sensitive peptide to form a novel MMP2 biosensor, named UCNP@p-QD. UCNP@p-QD was highly biocompatible according to cell viability assay. The FRET-based biosensor was employed in the MMP2 determination in vitro and in vivo. Furthermore, it was administrated into the tumor-bearing mouse to check MMP2 expression. UCNP@p-QD could be a promising tool for biological study and biomedical application. In this study, we demonstrated that the CIS/ZnS QD improved the upconversion intensity through a near-infrared-induced FRET process. This nanocomposite has the advantage of light penetration, excellent biocompatibility, and high sensitivity to sense MMP2. The near-infrared-induced composites are a potential inspiration for use in biomedical applications.

Multichannel Fluorescence Microscopy: Advantages of Going beyond a Single Emission

“…Thus, the fluorescence reporters can be tailored to respond to the presence of these specific macromolecules using functional peptides. [110][111][112][113] As an example, Chan et al [114] developed a nanocomposite formed by QDs attached to an upconverting nanoparticle (UCNP) which was able to change its emission color in the presence of matrix metalloproteinase 2 (MMP2), which is overexpressed in damaged and inflamed tissue, and in cells surrounding the invading front of metastatic tumors. The sensitivity of the nanocomposite emission to the presence of MMP2 was obtained through the functional peptide which linked the two types of NPs and allowed the FRET process to take place: the UCNPs emitted blue light under 800 nm excitation that was partially absorbed by the QDs which emitted red light (Figure 3A.1).…”

Emerging Biosensors for Oral Cancer Detection and Diagnosis—A Review Unravelling Their Role in Past and Present Advancements in the Field of Early Diagnosis

“…When compared to a standard sandwich ELISA system, the addition of 3DN-CNTs increased the sensitivity of a developed biosensor by almost twenty times [ 103 ]. Upconversion nanoparticles (UCNPs) [ 104 , 105 ], which display photon upconversion phenomena when activated by incident near-infrared (NIR) light with emission in the visible region of the electromagnetic spectrum, are other prominent types of NMs in biosensing. It has been reported that biocompatible UCNP composites based on fluorescence resonance energy transfer (FRET) may detect OSCC biomarkers using energy changes in the red and blue wavelength ranges.…”

The Peptide Functionalized Inorganic Nanoparticles for Cancer-Related Bioanalytical and Biomedical Applications

“…The peptide functionalized NPs have been extensively employed to construct biosensors/assays with various detection principles for detection of different analytes (some typical examples are included in Table 1 ) [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ,…”

“…With the multiple advantages including robust and high photostability, low toxicity, and deep tissue penetration with minimal autofluorescence background, UCNPs are rapidly emerging as strong contenders for the traditional down conversion-based fluorescence NPs/fluorescence dyes in biosensor construction because UCNPs are able to convert near-infrared (NIR) light into higher-energy and multicolor UV–visible emission light [ 6 , 7 , 8 ]. Recently, peptide-functionalized UCNP-based fluorescence resonance energy transfer (FRET) systems have been also used to detect various enzymes [ 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. UCNPs are normally synthesized in organic phase for obtaining high fluorescence quantum yield and low nanocrystal defect.…”