Extracellular vesicles (EVs), naturally occurring nanosized vesicles secreted from cells, are essential for intercellular communication. They carry unique biomolecules on the surface or interior that are of great interest as biomarkers for various pathological conditions such as cancer. In this work, we use highresolution atomic force microscopy (AFM) and spectroscopy (AFS) techniques to demonstrate differences between EVs derived from colon cancer cells and colon epithelial cells at the singlevesicle level. We observe that EV populations are significantly increased in the cancer cell media compared to the normal cell EVs. We show that both EVs display an EV marker, CD9, while EVs derived from the cancer cells are slightly higher in density. Hyaluronan (HA) is a nonsulfated glycosaminoglycan linked to malignant tumor growth according to recent reports. Interestingly, at the single-vesicle level, colon cancer EVs exhibit significantly increased HA surface densities compared to the normal EVs. Spectroscopic measurements such as Fourier transform infrared (FT-IR), circular dichroism (CD), and Raman spectroscopy unequivocally support the AFM and AFS measurements. To our knowledge, it represents the first report of detecting HA-coated EVs as a potential colon cancer biomarker. Taken together, this sensitive approach will be useful in identifying biomarkers in the early stages of detection and evaluation of cancer.
The
significant role of a vesicle is well recognized; however,
only lately has the advancement in biomedical applications started
to uncover their usefulness. Although the concept of vesicles originates
from cell biology, it later transferred to chemistry and material
science to develop nanoscale artificial vesicles for biomedical applications.
Herein, we examine different synthetic and biological vesicles and
their applications in the biomedical field in general. As our understanding
of biological vesicles increases, more suitable biomimicking synthetic
vesicles will be developed. The comparative discussion between synthetic
and natural vesicles for biomedical applications is a relevant topic,
and we envision this could enable the development of a proper approach
to realize the next-generation treatment goals.
To
realize a customizable biogenic delivery platform, herein we
propose combining cell-derived extracellular vesicles (EVs) derived
from breast cancer cell line MCF-7 with synthetic cationic liposomes
using a fusogenic agent, polyethylene glycol (PEG). We performed a
fluorescence resonance energy transfer (FRET)-based lipid-mixing assay
with varying PEG 1000 concentrations (0%, 15%, and 30%) correlated
with flow cytometry-based analysis and supported by dimensional analysis
by dynamic light scattering (DLS), transmission electron microscopy
(TEM), and atomic force microscopy (AFM) to validate our fusion strategy.
Our data revealed that these hybrid vesicles at a particular concentration
of PEG (∼15%) improved the cellular delivery efficiency of
a model siRNA molecule to the EV parental breast cancer cells, MCF-7,
by factors of 2 and 4 compared to the loaded liposome and EV precursors,
respectively. The critical rigidity/pliability balance of the hybrid
systems fused by PEG seems to be playing a pivotal role in improving
their delivery capability. This approach can provide clinically viable
delivery solutions using EVs.
Cancer
cells secrete extracellular vesicles (EVs) covered with
a carbohydrate polymer, hyaluronan (HA), linked to tumor malignancy.
Herein, we have unravelled the contour lengths of HA on a single cancer
cell-derived EV surface using single-molecule force spectroscopy (SMFS),
which divulges the presence of low molecular weight HA (LMW-HA <
200 kDa). We also discovered that these LMW-HA-EVs are significantly
more elastic than the normal cell-derived EVs. This intrinsic elasticity
of cancer EVs could be directly allied to the LMW-HA abundance and
associated labile water network on EV surface as revealed by correlative
SMFS, hydration dynamics with fluorescence spectroscopy, and molecular
dynamics simulations. This method emerges as a molecular biosensor
of the cancer microenvironment.
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