Journal of drug targeting
-
Journal of drug targeting · May 2006
EGFR-targeted immunoliposomes derived from the monoclonal antibody EMD72000 mediate specific and efficient drug delivery to a variety of colorectal cancer cells.
We hypothesized that immunoliposomes (ILs) constructed using Fab' from the humanized anti-EGFR monoclonal antibody, EMD72000, can provide efficient intracellular drug delivery in EGFR-overexpressing colorectal tumor cells. ILs were constructed modularly with various MAb fragments, including Fab' from EMD72000 (matuzumab) or C225 (cetuximab, Erbitux) covalently linked to stabilized liposomes containing chemotherapeutic drugs or probes. Immunoliposome preparation was optimized, including Fab' reduction and linkage, and evaluated for specific binding and cytotoxicity in epidermal growth factor receptor (EGFR)--overexpressing colorectal cancer cell lines in vitro. ⋯ ILs derived from EMD72000-Fab' were used to deliver doxorubicin to EGFR-overexpressing target cells in vitro. Immunoliposomal doxorubicin was significantly more cytotoxic than the corresponding non-targeted liposomal drug in target cells, such as HCT116, while equivalent in cells lacking EGFR-overexpression, such as Colo205. We conclude that EGFR-targeted ILs derived from the humanized MAb EMD72000 provide efficient and targeted delivery of anticancer drugs in colorectal cancer cells overexpressing EGFR.
-
Journal of drug targeting · May 2006
Enhancement of antitumor effect of doxorubicin by its complexation with gamma-cyclodextrin in pegylated liposomes.
In the present study, we examined tissue distribution and the antitumor effect of doxorubicin (DOX) after intravenous injection of the pegylated liposomes entrapping the DOX complex with gamma-cyclodextrin (gamma-CyD) (complex-in-liposome) in BALB/c mice bearing colon-26 tumor cells, compared with those of DOX solution, pegylated liposomes entrapping DOX alone (DOX-in-liposome), pegylated liposomes entrapping gamma-CyD (CyD-in-liposome) and the binary system of DOX-in-liposome and CyD-in-liposome. When injected to the mice, complex-in-liposome provided the high DOX levels in plasma and solid tumors, compared with the other preparations. Reflecting the result, complex-in-liposome elicited the retardation of tumor growth and the improvement of survival rate without suppression of increase in the body weight of mice. These results suggest the potential use of pegylated liposomes entrapping the DOX complex with gamma-CyD for a promising carrier for improvement of antitumor effects of DOX.
-
Double stranded short interfering RNAs (siRNAs) mediate gene silencing in a sequence specific manner. By virtue of their specific gene silencing activity and owing to the recent discoveries on their plasmid and virus driven expression, siRNAs are being widely adopted in research and therapeutics. ⋯ One major obstacle in developing RNA interference (RNAi) therapy is the delivery of siRNAs to the target cells. Combination of novel molecular targeting technologies, such as recombinant protein technology and ribosome display technology, will enable to deliver gene silencing agents to target cells specifically and efficiently.