Diabetic wounds are one of the debilitating complications that affect up to 20% of diabetic patients. Despite the advent of extensive therapies, the recovery rate is unsatisfactory, and approximately, 25% of patients undergo amputation, thereby demanding alternative therapeutic strategies. On the basis of the individual therapeutic roles of the miR-155 inhibitor and mesenchymal stem cells (MSC)derived exosomes, we conjectured that the combination of the miR-155 inhibitor and MSC-derived exosomes would have synergy in diabetic wound healing. Herein, miR-155-inhibitor-loaded MSC-derived exosomes showed synergistic effects in keratinocyte migration, restoration of FGF-7 levels, and anti-inflammatory action, leading to accelerated wound healing mediated by negative regulation of miR-155, using an in vitro co-culture model and in vivo mouse model of the diabetic wound. Furthermore, treatment with miR-155-inhibitor-loaded MSC-derived exosomes led to enhanced collagen deposition, angiogenesis, and re-epithelialization in diabetic wounds. This study revealed the therapeutic potential of miR-155-inhibitor-loaded MSC-derived exosomes in diabetic wound healing and opened the doors for encapsulating miRNAs along with antibiotics within the MSC-derived exosomes toward improved management of chronic, nonhealing diabetic wounds.
Cisplatin resistance is one of the
major concerns in the treatment
of oral squamous cell carcinoma (OSCC). Accumulating evidence suggests
microRNA (miRNA) dysregulation as one of the mediators of chemoresistance.
Toward this, our previous study revealed the role of exosomal microRNA-155
(miR-155) in cisplatin resistance via downregulation of FOXO3a, a
direct target of miR-155, and induction of epithelial-to-mesenchymal
transition in OSCC. In the present study, we demonstrate the therapeutic
potential of miR-155 inhibitor-laden exosomes in the sensitization
of a cisplatin-resistant (cisRes) OSCC 3D tumor spheroid
and xenograft mouse model. The cisRes OSSC 3D tumor spheroid
model recapitulated the hallmarks of solid tumors such as enhanced
hypoxia, reactive oxygen species, and secretory vascular endothelial
growth factor. Further treatment with miR-155 inhibitor-loaded exosomes
showed the upregulation of FOXO3a and induction of the mesenchymal-to-epithelial
transition with improved sensitization to cisplatin in cisRes tumor spheroids and xenograft mouse model. Moreover, the exosomal
miR-155 inhibitor suppressed the stem-cell-like property as well as
drug efflux transporter protein expression in cisplatin-resistant
tumors. Taken together, our findings, for the first time, established
that the miR-155 inhibitor-loaded exosomes reverse chemoresistance
in oral cancer, thereby providing an alternative therapeutic strategy
for the management of refractory oral cancer patients.
:
The discovery of miRNAs has been one of the revolutionary developments and has led to the advent
of new diagnostic and therapeutic opportunities for the management of cancer. In this regard, miRNA dysregulation has been shown to play a critical role in various stages of tumorigenesis, including tumor invasion, metastasis as well as angiogenesis. Therefore, miRNA profiling can provide accurate fingerprints for the development of diagnostic and therapeutic platforms. This review discusses the recent discoveries of miRNA-based
tools for early detection of cancer as well as disease monitoring in cancers that are common, like breast, lung,
hepatic, colorectal, oral and brain cancer. Based on the involvement of miRNA in different cancers as oncogenic miRNA or tumor suppressor miRNA, the treatment with miRNA inhibitors or mimics is recommended.
However, the stability and targeted delivery of miRNA remain the major limitations of miRNA delivery. In relation to this, several nanoparticle-based delivery systems have been reported which have effectively delivered
the miRNA mimics or inhibitors and showed the potential for transforming these advanced delivery systems
from bench to bedside in the treatment of cancer metastasis and chemoresistance. Based on this, we attempted
to uncover recently reported advanced nanotherapeutic approaches to deliver the miRNAs in the management
of different cancers.
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