Immunotherapy
is regarded as a potential strategy to combat cancer,
especially when immunotherapy is combined with appropriate chemotherapy.
However, the immunosuppressive tumor microenvironment (TME) and serious
side effects extremely limit the application of immunotherapy. Herein,
a self-stabilized hyaluronic acid nanoparticle is synthesized for
tumor-targeted delivery of doxorubicin (DOX), cisplatin (CDDP), and
resiquimod (R848) in osteosarcoma immunochemotherapy, which is referred
to as CDDPNPDOX&R848. CDDPNPDOX&R848 exhibits sufficient stability, great pH responsibility,
and brilliant tumor-targeting accumulation in vivo, which make it suitable for further in vivo applications.
After intravenous injection, CDDPNPDOX&R848 can release the loaded cargoes under the acidic TME continuously.
DOX can induce tumor cell apoptosis in combination with CDDP and trigger
immunogenic cell death. More importantly, the immune-activated TME
created by R848 can facilitate tumor-associated antigen presentation
and antitumor immunity elicitation. Benefiting from the synergistic
effect of chemotherapy and immunotherapy, the growth of tumors and
lung metastasis was greatly inhibited by CDDPNPDOX&R848 in the K7M2 orthotopic osteosarcoma mouse model. Thus, this intelligent
codelivery platform might be a competitive candidate for osteosarcoma
immunochemotherapy.
In oral squamous cell carcinoma (OSCC), abnormal expression of microRNAs has been extensively reported. MiR-let-7a has been validated as a critical regulator of multiple cancers, but the biological process involved and its potential role in OSCC remain unknown.We first analyzed the differential expression of miR-let-7a in cancer tissues, adjacent noncancerous tissues and cell lines. The functional role of miR-let-7a in OSCC cell lines was evaluated by using colony formation assays, cell proliferation and transwell invasion assays in vitro. In addition, subcutaneous xenotransplantation of miR-let-7a transfected cells into nude mouse model was carried out to explore the potential function of miR-let-7a in vivo.miR-let-7a levels were found to be significantly downregulated in OSCC tissues compared with matched normal tissues (n = 60), and lower expression of miR-let-7a was related to poor prognosis in OSCC patients. Overexpression of MiR-let-7a induced a suppression in proliferation, invasion and migration and inhibited tumourigenesis in the nude mouse model. We also determined that c-Myc may serve as a direct target of miR-let-7a; furthermore, upregulated c-Myc expression could partially rescue the effects caused by miR-let-7a overexpression. miR-let-7a is low expression in OSCC, and promotes tumor development by directly targeting c-Myc. Our results may provide a potential therapeutic role for miR-let-7a in human OSCC.
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