Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers

Abstract

Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy.

Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors

“…Also, EVs may be taken up by immune cells, leading to immunosuppression [17]. More recently, EVs have even gained a role in cancer diagnosis and therapy [18][19][20] as biomarker molecules that may be identified in different primary tumors with high sensitivity and specificity [21]. Regarding pancreatic cancer, Kalluri and colleagues found that glypican-1 (GPC1), a cell surface proteoglycan, is specifically enriched in circulating exosomes (30-200 nm endosome-derived EVs).…”

Effectiveness of a Controlled 5-FU Delivery Based on FZD10 Antibody-Conjugated Liposomes in Colorectal Cancer In vitro Models

“…The encapsulation efficiency (EE%) of 5-FU encapsulated in 5-FU/LPs or anti-FZD10/5-FU/LPs was evaluated according to the following formula: EE% = Wt/Wi × 100 where Wt is the amount of drug effectively incorporated into the liposomal formulation and Wi the total quantity of 5-FU initially added during the preparation. To evaluate the drug content, samples were lyophilized and treated with methanol (1:100 dilution) and then the absorbance spectra (Perkin Elmer Double beam UV-Visible Spectrophotometer Lambda Bio 20) were recorded at 265 nm versus a methanol solution containing the same lipid mixture used for liposome preparation (baseline) [ 20 ]. Three measurements were performed on three different batches for each liposomes formulation.…”

“…A constant Extra-High Tension (EHT) value of 3.00 kV and a working distance (WD) ranging from 1.8 to 3 mm were set for the FE-SEM observation. For each experiment and sample, a representative FE-SEM micrograph was selected after the collection of a set of images resulting from three replications of the same experiment [ 20 ].…”

“…The hydrodynamic diameter (size), the size distribution and the colloidal stability of the liposomal formulations were detected using a Zetasizer Nano ZS, Malvern Instruments Ltd., Worcestershire, UK (DTS 5.00), as previously reported [ 20 ]. Three measurements were performed on at least three different batches of each vesicles formulation, and results are reported together with the corresponding standard deviation.…”

“…Indeed, numerous studies proved that FZDs play a crucial role in different cancer functions, thus promoting proliferation, migration, invasion, angiogenesis, and also chemoresistance. Furthermore, modulation of expression levels for specific FZD depending on up- or downregulation of the corresponding messenger RNA (mRNA) was observed in different cancers tissues [ 15 , 16 , 17 , 18 , 19 , 20 ]. Among the FZD proteins, FZD10 was suggested to be one of the most promising receptors for the development of targeted therapy of CRC.…”