SERS Quantification of Galunisertib Delivery in Colorectal Cancer Cells by Plasmonic‐Assisted Diatomite Nanoparticles

Abstract

therapies for CRC treatment, like systemic chemotherapy and immunotherapy, are expensive and invasive since they fail to target cancer cells selectively, causing severe toxicity on normal tissues besides side effects. [2][3][4][5] The epithelial-to-mesenchymal transition (EMT) is a dynamic multistep process involved in several physiological and pathological conditions, including cancer. [6] Notably, EMT in CRC is associated with an invasive, metastatic, and chemoresistant phenotype. [7] In contrast, the mesenchymal-to-epithelial transition (MET), is the reverse program of EMT in metastases and is characterized by the upregulation of epithelial adhesive proteins such as E-CADHERIN, and downregulation of mesenchymal proteins, such as SNAIL-1 and TWIST-1. Slowing EMT or even reversing the process in metastases inducing a MET program not only is a powerful therapeutic approach alone, but can also assist in increasing the efficacy of other anticancer treatments. Among the molecular pathways promoting tumorigenesis in CRC, the transforming growth factor-β (TGF-β) is described as a crucial factor in EMT induction. [8] Fighting the CRC with the TGF-β receptor I-specific inhibitor Galunisertib (LY2157299, LY) has been proposed as a powerful strategy to reduce tumor growth and the risk of relapse. [8] However, LY is cleared predominantly by cytochrome P450 3A4 (CYP3A4) oxidative metabolism in the The small molecule Galunisertib (LY2157299, LY) shows multiple anticancer activities blocking the transforming growth factor-β1 receptor, responsible for the epithelial-to-mesenchymal transition (EMT) by which colorectal cancer (CRC) cells acquire migratory and metastatic capacities. However, frequent dosing of LY can produce highly toxic metabolites. Alternative strategies to reduce drug side effects can rely on nanoscale drug delivery systems that have led to a medical revolution in the treatment of cancer, improving drug efficacy and lowering drug toxicity. Here, a hybrid nanosystem (DNP-AuNPs-LY@Gel) made of a porous diatomite nanoparticle decorated with plasmonic gold nanoparticles, in which LY is retained by a gelatin shell, is proposed. The multifunctional capability of the nanosystem is demonstrated by investigating the efficient LY delivery, the enhanced EMT reversion in CRCs and the intracellular quantification of drug release with a sub-femtogram resolution by surface-enhanced Raman spectroscopy (SERS). The LY release trigger is the pH sensitivity of the gelatin shell to the CRC acidic microenvironment. The drug release is real-time monitored at single-cell level by analyzing the SERS signals of LY in CRC cells. The higher efficiency of LY delivered by the DNP-AuNPs-LY@Gel complex paves the way to an alternative strategy for lowering drug dosing and consequent side effects.

Biosensing Using SERS Active Gold Nanostructures

“…SERS-based sensors can be used to monitor certain physiological processes as well as the real-time release of drugs in living cells [124]. Managò et al, recently demonstrated the use of hybrid nanoparticles, consisting of diatomite nanoparticles decorated with gold nanospheres and covered by a pH-sensitive gelatin shell, for label-free imaging of the nanovector localization and local SERS-sensing of the intracellular release of galunisertib in living colorectal cancer cells (see Figure 8e-g).…”

Underwater Light Manipulation by the Benthic Diatom Ctenophora pulchella: From PAR Efficient Collection to UVR Screening

“…In particular, it has been observed the ability of valves of several centric species to collect and confine photosynthetic active radiation (PAR) in intense hot-spots [15][16][17], and, in several cases, both valves and girdles have shown to behave like photonic crystal slabs [18,19]. Since the XIX century up to recent days, physical and chemical properties of the frustule have been exploited in several fields [20], comprising microscope objectives quality testing [7], water filtration [21], forensic science [22], optics and photonics [19,23], plasmonics [24,25], catalysis [26], biochemical sensing [27,28], solar energy harvesting [29,30], biomedicine and drug delivery [31,32].…”

SERS Sensing of Bacterial Endotoxin on Gold Nanoparticles

“…When an incident laser beam interacts with metallic nanostructures, plasma oscillations of metallic NPs enhance the Raman signals of molecules adsorbed or close to the metallic surface up to 6-7 orders of magnitude (15). Therefore, due to the Raman fingerprint, SERS-based sensing allows to identify and quantify molecules with excellent sensitivity and reproducibility in different environments, thereby enabling the use of the SERS technique for numerous biomedical and biosensing applications (16)(17)(18)(19)(20). Indirect SERS sensing, based on the combined use of a SERS tag and a selective aptamer-based binding, has been demonstrated for quantitative detection of endotoxins in a solution (21).…”