Myriad of advancement has been made to identify naturally abundant substances for use as therapeutic agents. Host defence peptides (eukaryotic cells) from animal venoms have been identified to possess substantial anticancer properties. However, their therapeutic potential cannot be fully realized without acontrolled delivery mechanism because of off-target toxicity, non-specificity, complement activation issues and unfavorable pharmacokinetics, all contributed to negatively to translate these agents to clinic. Towards a safer, translatable approach, we have developed a viable chemical methodology based on well-defined, self-assembled polymeric nano-architecture for controlled delivery of venom peptides.?Although our methodology is applicable for peptides of 5-30 aa, as a specific example, a well-studied cytolytic peptide, Melittin (26 aa), was selected for preliminary studies. The melitin-incorporated polymeric nanoparticles (hydrodynamic diameter: 50 � 5nm) were prepared by applying a post-incubation methodology. The parent nanoparticles were self-assembled as aqueous suspension of amphiphilic diblock-co-polymer PS-b-PAA and Polyoxyethylene (20) cetyl ether. These particles showed significant stability over time and the release of melittin remained well controlled in time and concentration dependent manner. The cytotoxicity of these nanoparticles was studied in MCF-7 and MDA-MB231 breast cancer cells using MTT assay and showed IC50 value of 50nM. This construct promises to address the serious off-target toxicity of the membrane-bound venom peptides when systemically delivered and simultaneously protects the integrity of the peptide itself that may complicate systemic application. The presentation will discuss characterization and application of these particles using dynamic light scattering, atomic force microscopy, transmission electron microscopy, electrophoretic potential, and cytotoxicity analysis. We anticipate this unique anticancer agent found in nature coupled with the delivery approach has the potential for the development of a novel anticancer treatment.

Controlled and safer therapeutic delivery of venom toxins using well-defined polymeric nanoparticles for cancer inhibition

248th National Meeting (2014)

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