Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs
Sun-Hee Cho,1,* Ji Hyeon Hong,2,* Young-Woock Noh,1 Eunji Lee,2 Chang-Soo Lee,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 2Graduate School of Analytical Science and Technology, Chungnam National University...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2016
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4b73bc8c609e413da542129c2e604bb5 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4b73bc8c609e413da542129c2e604bb5 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4b73bc8c609e413da542129c2e604bb52021-12-02T02:41:15ZRaspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs1178-2013https://doaj.org/article/4b73bc8c609e413da542129c2e604bb52016-10-01T00:00:00Zhttps://www.dovepress.com/raspberry-like-polygamma-glutamic-acid--hydrogel-particles-for-ph-depe-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sun-Hee Cho,1,* Ji Hyeon Hong,2,* Young-Woock Noh,1 Eunji Lee,2 Chang-Soo Lee,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 2Graduate School of Analytical Science and Technology, Chungnam National University, 3Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: In this research, we synthesized bioderived poly(amino acid) hydrogel particles that showed pH-dependent membrane-disrupting properties and controlled cytosolic delivery of antitumor drugs. Poly(γ-glutamic acid) (γ-PGA) that has been produced extensively using bacteria, especially those of Bacillus subtilis species, was modified with cholesterol (γ-PGA/Chol), and the γ-PGA/Chol conjugates were used to form polymeric nanoparticles the size of 21.0±1.1 nm in aqueous solution. When the polymeric nanoparticles were mixed with doxorubicin (Dox), raspberry-like hydrogel particles (RBHPs) were formed by the electrostatic interaction between the cationically charged Dox and the anionically charged nanoparticles. The average size and surface charge of the RBHPs in aqueous solution were 444.9±122.5 nm and -56.44 mV, respectively. The loaded amount of Dox was approximately 63.9 µg/mg of RBHPs. The RBHPs showed controlled drug release behavior in both in vitro and ex vivo cell-based experiments. Through fluorescence microscopy and fluorescence-activated cell sorting, the cellular uptake of RBHPs into human cervical cancer cells (HeLa) was analyzed. The cytotoxic effect, evaluated by the methyl tetrazolium salt assay, was dependent on both the concentration of RBHPs and the treatment time. The pH-dependent membrane-disrupting properties of the RBHPs and the subsequent cytosolic delivery of Dox were evaluated using a standard hemolysis assay. Upon an increase in hydrophobicity at the lysosomal acidic pH, RBHPs could easily interact, penetrate cell membranes, and destabilize them. Taken together, the data suggested that RBHPs could be used as drug delivery carriers after loading with other therapeutic drugs, such as proteins or small interfering RNA for cancer therapy. Keywords: hydrogel particles, controlled release, endosomal escape, antitumorCho SHHong JHNoh YWLee ELee CSLim YTDove Medical Pressarticlehydrogel particlescytosolic deliveryantitumornanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5621-5632 (2016) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
hydrogel particles cytosolic delivery antitumor nanoparticles Medicine (General) R5-920 |
| spellingShingle |
hydrogel particles cytosolic delivery antitumor nanoparticles Medicine (General) R5-920 Cho SH Hong JH Noh YW Lee E Lee CS Lim YT Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| description |
Sun-Hee Cho,1,* Ji Hyeon Hong,2,* Young-Woock Noh,1 Eunji Lee,2 Chang-Soo Lee,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 2Graduate School of Analytical Science and Technology, Chungnam National University, 3Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: In this research, we synthesized bioderived poly(amino acid) hydrogel particles that showed pH-dependent membrane-disrupting properties and controlled cytosolic delivery of antitumor drugs. Poly(γ-glutamic acid) (γ-PGA) that has been produced extensively using bacteria, especially those of Bacillus subtilis species, was modified with cholesterol (γ-PGA/Chol), and the γ-PGA/Chol conjugates were used to form polymeric nanoparticles the size of 21.0±1.1 nm in aqueous solution. When the polymeric nanoparticles were mixed with doxorubicin (Dox), raspberry-like hydrogel particles (RBHPs) were formed by the electrostatic interaction between the cationically charged Dox and the anionically charged nanoparticles. The average size and surface charge of the RBHPs in aqueous solution were 444.9±122.5 nm and -56.44 mV, respectively. The loaded amount of Dox was approximately 63.9 µg/mg of RBHPs. The RBHPs showed controlled drug release behavior in both in vitro and ex vivo cell-based experiments. Through fluorescence microscopy and fluorescence-activated cell sorting, the cellular uptake of RBHPs into human cervical cancer cells (HeLa) was analyzed. The cytotoxic effect, evaluated by the methyl tetrazolium salt assay, was dependent on both the concentration of RBHPs and the treatment time. The pH-dependent membrane-disrupting properties of the RBHPs and the subsequent cytosolic delivery of Dox were evaluated using a standard hemolysis assay. Upon an increase in hydrophobicity at the lysosomal acidic pH, RBHPs could easily interact, penetrate cell membranes, and destabilize them. Taken together, the data suggested that RBHPs could be used as drug delivery carriers after loading with other therapeutic drugs, such as proteins or small interfering RNA for cancer therapy. Keywords: hydrogel particles, controlled release, endosomal escape, antitumor |
| format |
article |
| author |
Cho SH Hong JH Noh YW Lee E Lee CS Lim YT |
| author_facet |
Cho SH Hong JH Noh YW Lee E Lee CS Lim YT |
| author_sort |
Cho SH |
| title |
Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| title_short |
Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| title_full |
Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| title_fullStr |
Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| title_full_unstemmed |
Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| title_sort |
raspberry-like poly(γ-glutamic acid) hydrogel particles for ph-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/4b73bc8c609e413da542129c2e604bb5 |
| work_keys_str_mv |
AT chosh raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs AT hongjh raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs AT nohyw raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs AT leee raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs AT leecs raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs AT limyt raspberrylikepolygammaglutamicacidhydrogelparticlesforphdependentcellmembranepassageandcontrolledcytosolicdeliveryofantitumordrugs |
| _version_ |
1718402282884694016 |