Fluorescent nanodiamonds (FNDs) are nontoxic and photostable nanomaterials, ideal for long-term in vivo imaging applications. This paper reports that FNDs with a size of approximately 140 nm can be covalently conjugated with folic acid (FA) for receptor-mediated targeting of cancer cells at the single-particle level. The conjugation is made by using biocompatible polymers, such as polyethylene glycol, as crosslinked buffer layers. Ensemble-averaged measurements with flow cytometry indicate that more than 50% of the FA-conjugated FND particles can be internalized by the cells (such as HeLa cells) through receptor-mediated endocytosis, as confirmed by competitive inhibition assays. Confocal fluorescence microscopy reveals that these FND particles accumulate in the perinuclear region. The absolute number of FNDs internalized by HeLa cells after 3 h of incubation at a particle concentration of 10 microg mL(-1) is in the range of 100 particles per cell. The receptor-mediated uptake process is further elucidated by single-particle tracking of 35-nm FNDs in three dimensions and real time during the endocytosis.
Hydrogels
with robust wet adhesion are desirable for
applications
in aqueous environments. Wet adhesion arising from synergy between
hydrophobic and catechol components in mussel foot proteins has been
highlighted. However, optimizing hydrogels with multiple components
is challenging because of their complex structure–property
relationships. Herein, high-throughput screening of a series of hydrophobic
alkyl monomers and adhesive catechol derivatives was used to systematically
develop wet adhesive hydrogels. Short alkyl chains promote wet adhesion
by repelling water at the adhesive interface, whereas long alkyl chains
form strong hydrophobic interactions inside the hydrogel network that
impede or dissipate energy for wet adhesion. The optimized wet adhesive
hydrogel, containing short alkyl chain, was applied for rapid hemostasis
and wound healing because of the synergistic effect of catechol and
alkyl groups and its immunomodulation ability, which is revealed through
a transcriptomic analysis. Conductive nanocomponents were incorporated
into the optimized hydrogel to produce a wearable device, which was
used for continuous monitoring human electrocardiogram (ECG) during
swimming, and in situ epicardial ECG on a porcine living and beating
heart. This study demonstrated an efficient and generalized molecular
design strategy for multifunctional wet adhesive hydrogels.
Background
This study investigated the use of nanodiamond particles (NDs) as a promising material for drug delivery in vivo and in vitro.
Methods
HepG2 cells (a human hepatic carcinoma cell line) were used to determine the characteristics of a nanodiamond-doxorubicin complex (ND-DOX) when taken up by cells in vitro using laser scanning confocal microscopy and dialysis experiments. We also compared the survival rate and histopathology of tumor-bearing mice after treatment with NDs or ND-DOX in vivo.
Results
In vitro investigation showed that ND-DOX has slow and sustained drug release characteristics compared with free doxorubicin. In vivo, the survival rate of tumor-bearing mice treated with ND-DOX was four times greater than that of mice treated with free doxorubicin. Interestingly, the survival rate in mice treated with NDs alone was close to that of mice treated with free doxorubicin. This indicates that treatment with ND-DOX can prolong the lifespan of tumor-bearing mice significantly compared with conventional doxorubicin and that NDs can have this effect as well. Histopathological analysis showed that neither the NDs nor ND-DOX were toxic to the kidney, liver, or spleen in contrast with the well-known toxic effects of free doxorubicin on the kidney and liver. Further, both the bare NDs and ND-DOX could suppress tumor growth effectively.
Conclusion
NDs can potentially prolong survival, and ND-DOX may act as a nanodrug with promising chemotherapeutic efficacy and safety.
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