Regeneration
and functional recovery of peripheral nerves remain formidable due
to the inefficient physical and chemical cues in the available nerve
guidance conduits (NGCs). Introducing micropatterns and bioactive
substances into the inner wall of NGCs can effectively regulate the
behavior of Schwann cells, the elongation of axons, and the phenotype
of macrophages, thereby aiding the regeneration of injured nerve.
In this study, linear micropatterns with ridges and grooves of 3/3,
5/5, 10/10, and 30/30 μm were created on poly(d,l-lactide-co-caprolactone) (PLCL) films following
with surface aminolysis and electrostatic adsorption of graphene oxide
(GO) nanosheets. The GO-modified micropatterns could significantly
accelerate the collective migration of Schwann cells (SCs) and migration
of SCs from their spheroids in vitro. Moreover, the SCs migrated directionally
along the stripes with a fastest rate on the 3/3-GO film that had
the largest cell adhesion force. The neurites of N2a cells were oriented
along the micropatterns, and the macrophages tended to differentiate
into the M2 type on the 3/3-GO film judged by the higher expression
of Arg 1 and IL-10. The systematic histological and functional assessments
of the regenerated nerves at 4 and 8 weeks post-surgery in vivo confirmed
that the 3/3-GO NGCs had better performance to promote the nerve regeneration,
and the CMAP, NCV, wet weight of gastrocnemius muscle, positive S100β
and NF200 area percentages, and average myelinated axon diameter were
more close to those of the autograft group at 8 weeks. This type of
NGCs thus has a great potential for nerve regeneration.
Tumor-associated
macrophages (TAMs) that exist in tumor microenvironment
promote tumor progression and have been suggested as a promising therapeutic
target for cancer therapy in preclinical studies. Development of theranostic
systems capable of specific targeting, imaging, and ablation of TAMs
will offer clinical benefits. Here we constructed a theranostic probe,
namely, TPE-Man, by attaching mannose moieties to a red-emissive and
AIE (aggregation-induced emission)-active photosensitizer. TPE-Man
can specifically recognize a mannose receptor that is overexpressed
on TAMs by the sugar–receptor interaction and enables fluorescent
visualization of the mannose-receptor-positive TAMs in high contrast.
The histologic study of mouse tumor sections further verifies TPE-Man’s
excellent targeting specificity being comparable with the commercial
mannose-receptor antibody. TAMs can be effectively eradicated upon
exposure to white light irradiation via a photodynamic therapy effect.
To our knowledge, this is the first small molecular theranostic probe
for TAMs that revealed combined advantages of low cost, high targeting
specificity, fluorescent light-up imaging, and efficient photodynamic
ablation.
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