Novel pH responsive vesicles for siRNA delivery to the tumor.

In the last decades anticancer therapy has devoted many efforts in developing supramolecular drug carriers based on the physical assembly of “smart” polymers. These systems can be exploited to improve the site selectivity to target tissues preserving the therapeutic activity of unstable drugs while reducing their systemic side-effects. Block amphiphilic copolymers can be assembled in vesicles that can be loaded with hydrophilic and/or hydrophobic drugs. In this work we have synthesized a triblock pH-responsive polymer to be assembled in vesicles for the delivery of siRNA to cancer cells with the aim of engineering a colloidal drug delivery system able to undergo passive accumulation in the cancer tissue by EPR effect. Introduction of folic acid ligands able to target folic acid receptor FR-α, overexpressed by many cancer tissues1, at the surface of the vesicles will confer active targeting capacity to the system. The vesicles forming polymer was synthesized in order to respond to the acid environment in the endosomal compartment with prompt disassembly of the nanocarrier and consequent siRNA release. Appropriate siRNA sequence will be chosen to silence the expression of the α1 subunit of the Na+/K+ATPase that is often upregulated in lung cancer cells and selectively reduce their proliferation2.