Treatment of Dutch rat models of glioma using EphrinA1-PE38/GM-CSF chitosan nanoparticles by in situ activation of dendritic cells

Abstract

Although dendritic cells (DCs) used in DC-based immunotherapy are loaded with tumor-associated antigens, the antitumor immune response is effectively stimulated in cytotoxic specific T lymphocytes (CTLs), thereby achieving targeted killing of tumor cells without harming surrounding normal cells. This makes it a highly promising new form of therapy. In this study, we successfully created chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles and transplanted them into tumor-bearing rats, resulting in the effective killing of glioma tissue and a prolonged life span. Further immunohistochemistry and flow cytometry studies revealed that the treatment was effective in increasing the number of dendritic cell activations under an immunomodulatory response. These results suggest that chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles may be effective in inducing in situ activation of DCs in glioma-bearing rats, thereby generating DC vaccines in vivo.

Eph Receptor Tyrosine Kinases in Tumor Immunity

“…Additionally, ephrin-A1 has been used to activate DCs in a rat glioma model (22). The data from these preclinical models suggest that these DC vaccines induce immune responses and decrease tumor burden, though the findings invite further investigation.…”

<p>Nanoparticle Drug Delivery System for Glioma and Its Efficacy Improvement Strategies: A Comprehensive Review</p>

“…57 Dendritic polymers can improve drug release and biocompatibility. 58 Macromolecular block copolymer micelles have a long cycle capacity and high stability. 59…”

Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications

“…For example, liposomes, microspheres, gels and biodegradable polymer nanoparticles are being engineered to replace conventional formulations and administration methods, and have demonstrated early success, particularly in cancer therapy (see summary Table 2) [142][143][144][145]. Nanoparticle Chitosan-coated Ephrin-A1-PE38/GM-CSF nanoparticles [163] Eph-targeted liposomes have been formulated for the delivery of multiple therapeutic cargoes, including small molecule therapeutics, miRNAs, siRNAs and gene therapies. Efforts to target liposomes to Eph receptors include the EphA2-targeted delivery of doxorubicin and siRNA from nanoliposomes [146], EphA10-targeted delivery of doxorubicin and siRNA from lipoplexes [147], and EphA2-targeted delivery of doxorubicin from liposomes [148].…”

“…Nanoparticles have also been used to deliver novel recombinant proteins. For example, chitosan-coated nanoparticles bearing the recombinant protein Ephrin-A1-PE38/GM-CF were demonstrated to have anti-tumor activity in rats [163].…”