Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.
Uveal melanoma (UM) is the most common primary intraocular
malignancy
in adults. However, challenges in early diagnosis, high risk of liver
metastasis, and lack of effective targeted therapy lead to poor prognosis
and high mortality of UM. Therefore, generating an effective molecular
tool for UM diagnosis and targeted treatment is of great significance.
In this study, a UM-specific DNA aptamer, PZ-1, was successfully developed,
which could specifically distinguish molecular differences between
UM cells and noncancerous cells with nanomolar-range affinity and
presented excellent recognition ability for UM in vivo and clinical
UM tissues. Subsequently, the binding target of PZ-1 on UM cells was
identified as JUP (junction plakoglobin) protein, which held great
potential as a biomarker and therapeutic target for UM. Meanwhile,
the strong stability and internalization capacity of PZ-1 were also
determined, and a UM-specific aptamer-guided “nanoship”
was engineered to load and selectively release doxorubicin (Dox) to
targeted UM cells, with lower toxicity to nontumor cells. Taken together,
the UM-specific aptamer PZ-1 could serve as a molecular tool to discover
the potential biomarker for UM and to achieve the targeted therapy
of UM.
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