Multifunctional Envelope-type Nano Device as non-viral gene delivery system for cancer therapy

In this study, we developed a multifunctional envelope-type nano device (MEND) as a non-viral siRNA delivery system for cancer, which can induce the knockdown of tumor specific genes and anti-tumor effect with no toxicity. First, we measured antigen presentation of OVA encapsulated R8-MEND in dendritic cell (DC). As a result, R8-MEND showed specific MHC class I presentation, although showed low MHC class II presentation. Moreover, mice subcutaneously immunized by R8-MEND were showed significant antitumor effect compared with control mice. Next, we prepared GALA/DMEND encapsulating siRNA core condensed with protamine. To investigate antitumor effects, we immunized DCs which were silenced SOCS1 by GALA/DMEND to mice. As a result, SOCS1- silenced DC significantly suppressed tumor growth compared with control DC. Therefore, we succeeded in enhancing antitumor effect by silencing SOCS1 of DC with GALA/DMEND. For systemic siRNA delivery, HT1080 cells were s.c. inoculated into nude mice. After i.v. injection to tumor-bearing mice, GALA/PEG-MEND exhibited high systemic stability and accumulated in tumor tissue. Target □-actin expression in tumor tissue was knockdowned more than 60% after administration of GALA/PEG-MEND (4mg siRNA/kg), which resulted in suppression of tumor growth (特願2010-39667). Serum level of ALT remained normal value, and body weight was unchanged after i.v. administration of GALA/PEG-MEND. These results suggested that GALA/PEG-MEND should be a valuable siRNA delivery system for in vivo tumor and siRNA therapeutics.

In this study, we developed a multifunctional envelope-type nano device (MEND) as a non-viral siRNA delivery system for cancer, which can induce the knockdown of tumor specific genes and anti-tumor effect with no toxicity. First, we measured antigen presentation of OVA encapsulated R8-MEND in dendritic cell (DC). As a result, R8-MEND showed specific MHC class I presentation, although showed low MHC class II presentation. Moreover, mice subcutaneously immunized by R8-MEND were showed significant antitumor effect compared with control mice. Next, we prepared GALA/DMEND encapsulating siRNA core condensed with protamine. To investigate antitumor effects, we immunized DCs which were silenced SOCS1 by GALA/DMEND to mice. As a result, SOCS1- silenced DC significantly suppressed tumor growth compared with control DC. Therefore, we succeeded in enhancing antitumor effect by silencing SOCS1 of DC with GALA/DMEND. For systemic siRNA delivery, HT1080 cells were s.c. inoculated into nude mice. After i.v. injection to tumor-bearing mice, GALA/PEG-MEND exhibited high systemic stability and accumulated in tumor tissue. Target □-actin expression in tumor tissue was knockdowned more than 60% after administration of GALA/PEG-MEND (4mg siRNA/kg), which resulted in suppression of tumor growth (特願2010-39667). Serum level of ALT remained normal value, and body weight was unchanged after i.v. administration of GALA/PEG-MEND. These results suggested that GALA/PEG-MEND should be a valuable siRNA delivery system for in vivo tumor and siRNA therapeutics.