Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery

Young Wook Won, Sun Mi Yoon, Chung Hee Sonn, Kyung-Mi Lee, Yong Hee Kim

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3839-3848
Number of pages10
JournalACS Nano
Volume5
Issue number5
DOIs
Publication statusPublished - 2011 May 24

Fingerprint

tanespimycin
gelatins
Succinic Acid
Gelatin
inhibitors
Self assembly
self assembly
delivery
Nanoparticles
nanoparticles
Tumors
drugs
tumors
Biocompatible Materials
Biomaterials
HSP90 Heat-Shock Proteins
polysaccharides
biocompatibility
Dynamic light scattering
Polysaccharides

Keywords

  • 17-AAG
  • Alpha-tocopheryl succinate
  • Anticancer drug delivery
  • Nanoparticles
  • Recombinant human gelatin
  • Self-assembly

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery. / Won, Young Wook; Yoon, Sun Mi; Sonn, Chung Hee; Lee, Kyung-Mi; Kim, Yong Hee.

In: ACS Nano, Vol. 5, No. 5, 24.05.2011, p. 3839-3848.

Research output: Contribution to journalArticle

Won, Young Wook ; Yoon, Sun Mi ; Sonn, Chung Hee ; Lee, Kyung-Mi ; Kim, Yong Hee. / Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery. In: ACS Nano. 2011 ; Vol. 5, No. 5. pp. 3839-3848.
@article{c82b40982eb8447f9200f98ea65d8413,
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.",
keywords = "17-AAG, Alpha-tocopheryl succinate, Anticancer drug delivery, Nanoparticles, Recombinant human gelatin, Self-assembly",
author = "Won, {Young Wook} and Yoon, {Sun Mi} and Sonn, {Chung Hee} and Kyung-Mi Lee and Kim, {Yong Hee}",
year = "2011",
month = "5",
day = "24",
doi = "10.1021/nn200173u",
language = "English",
volume = "5",
pages = "3839--3848",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery

AU - Won, Young Wook

AU - Yoon, Sun Mi

AU - Sonn, Chung Hee

AU - Lee, Kyung-Mi

AU - Kim, Yong Hee

PY - 2011/5/24

Y1 - 2011/5/24

N2 - 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.

AB - 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.

KW - 17-AAG

KW - Alpha-tocopheryl succinate

KW - Anticancer drug delivery

KW - Nanoparticles

KW - Recombinant human gelatin

KW - Self-assembly

UR - http://www.scopus.com/inward/record.url?scp=80051497797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051497797&partnerID=8YFLogxK

U2 - 10.1021/nn200173u

DO - 10.1021/nn200173u

M3 - Article

VL - 5

SP - 3839

EP - 3848

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 5

ER -