Unit polyion complex (uPIC) nanocarrier for siRNA delivery to glioblastoma and pancreatic cancer, Cancer Science

There are critical issues in siRNA therapeutics, as follows, 1) siRNA is immediately degraded in extracellular milieu, such as bloodstream, 2) the size of siRNA is -5nm, so siRNA is readily excreted from the kidney to the urine, and 3) the negative charge of siRNA repels the negatively charged cell membrane, inhibiting the cellular uptake of siRNA. Thus, many previous studies have encapsulated siRNA into -100 nm-sized nanoparticles to stabilize it. However, refractory cancers have tight barriers that prevent the penetration of such nanoparticles into cancer cells. To overcome these hurdles, a new type of siRNA nanocarrier is developed for the cancer-targeted siRNA delivery, using a Y-shaped block catiomer (YBC) with precisely regulated chain length and precisely neutralize their charges. Indeed, two YBCs are bound to a single siRNA in the bloodstream, generating a dynamic polyin-pair, termed uPIC. Owing to both high stability in the bloodstream and ultra-small (or optimal) size (-18 nm) to penetrate fibrotic tissues, uPIC efficiently delivers siRNA into murine models of fibrotic pancreatic cancer and glioblastoma, exerting the significant anticancer activity in vivo.