title: Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery.
abstract: A wide variety of drug delivery systems have been developed for the delivery of anticancer agents. One of the most frequently used natural biomaterials in drug delivery systems is polysaccharides; however, they are difficult to digest and to eliminate from the body after systemic administration due to their high molecular weight natures and the absence of degrading enzymes. Therefore, the development of degradable and eliminable natural biomaterials is critical for successful in vivo applications. In the present study, we report the development of self-assembled biodegradable nanoparticles based on recombinant human gelatin (rHG) modified with alpha-tocopheryl succinate (TOS). The rHG-TOS nanoparticles efficiently encapsulated 17-AAG (17-allylamino-17-demethoxygeldanamycin), a small molecular anticancer drug targeting heat shock protein 90. The formation of 17-AAG-loaded nanoparticles was confirmed using TEM and dynamic light scattering analysis and found to be within the size of 90-220 nm. The loading efficiency, sustained release pattern, and stability of 17-AAG from the rHG-TOS nanoparticles were determined using HPLC. Furthermore, the passive targeting of rHG-TOS nanoparticles to the tumor area via enhanced permeability and retention effect was examined by noninvasive live animal imaging in a tumor mouse model. Finally, the 17-AAG-loaded nanoparticles were nonimmunogenic and more efficient than free 17-AAG in manifesting an anticancer effect in the tumor model. Overall, our data demonstrate rHG-TOS as a promising tool for the delivery of 17-AAG featuring therapeutic efficacy and biocompatibility.
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, 17, Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Yoon
authors.forename: Chung Hee
authors.initials: CH
authors.lastname: Sonn
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D005780:Gelatin / Q000737:chemistry* / Q000235:genetics; D005960:Glucosides / Q000737:chemistry / Q000627:therapeutic use*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: C424886:17-aldehedeyloxy-19-glucopyranosyloxy-lab-8,13-dien-15-iol; D005960:Glucosides; D018841:HSP90 Heat-Shock Proteins; D053769:Nanocapsules; D011994:Recombinant Proteins; D013729:Terpenes; D005780:Gelatin; D024502:alpha-Tocopherol