-
Je něco špatně v tomto záznamu ?
Polycation fluorination improves intraperitoneal siRNA delivery in metastatic pancreatic cancer
Y. Hang, S. Tang, W. Tang, D. Větvička, C. Zhang, Y. Xie, F. Yu, A. Yu, D. Sil, J. Li, RK. Singh, D. Oupický
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
R01 CA228524
NCI NIH HHS - United States
R01 CA235863
NCI NIH HHS - United States
- MeSH
- halogenace * MeSH
- lidé MeSH
- malá interferující RNA MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní * farmakoterapie MeSH
- polyelektrolyty MeSH
- tkáňová distribuce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Intraperitoneal (IP) administration of therapeutics promises to help the treatment of cancers originated from organs in the peritoneal cavity. In this study, we evaluated how physicochemical properties of self-assembled polycation/siRNA nanoparticles affect their IP delivery efficacy in an orthotopic PDAC model. We have examined the effect of covalent polycation modification with lipophobic and hydrophobic tetrafluoro-p-toluic acid (TFTA), hydrophobic cholesterol, and hydrophilic poly(ethylene glycol) respectively. The surface charge of the three different nanoparticles was also modulated by coating the surface with serum albumin. We found that positively charged fluorine-containing particles with lipophobic properties based on a mixture of positively charged polymeric AMD3100 CXCR4 antagonist (PAMD) and PAMD modified with TFTA (mPAMD-TFTA)/siRNA displayed the best cell uptake and transfection efficacy in vitro. Biodistribution evaluation of the nanoparticles in a syngeneic orthotopic PDAC model revealed that the fluorine-containing formulation also achieved the highest PDAC tumor accumulation after IP administration. With a combination of CXCR4 inhibition by PAMD and PLK1 downregulation by siRNA, the treatment with mPAMD-TFTA/siPLK1 showed significant inhibition of both primary and metastatic PDAC tumors. Overall, our study provides insights into and guides the design of the nanoparticles for improved IP delivery of siRNA in PDAC.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21025747
- 003
- CZ-PrNML
- 005
- 20211026133541.0
- 007
- ta
- 008
- 211013s2021 ne f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.jconrel.2021.03.028 $2 doi
- 035 __
- $a (PubMed)33774121
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ne
- 100 1_
- $a Hang, Yu $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 245 10
- $a Polycation fluorination improves intraperitoneal siRNA delivery in metastatic pancreatic cancer / $c Y. Hang, S. Tang, W. Tang, D. Větvička, C. Zhang, Y. Xie, F. Yu, A. Yu, D. Sil, J. Li, RK. Singh, D. Oupický
- 520 9_
- $a Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Intraperitoneal (IP) administration of therapeutics promises to help the treatment of cancers originated from organs in the peritoneal cavity. In this study, we evaluated how physicochemical properties of self-assembled polycation/siRNA nanoparticles affect their IP delivery efficacy in an orthotopic PDAC model. We have examined the effect of covalent polycation modification with lipophobic and hydrophobic tetrafluoro-p-toluic acid (TFTA), hydrophobic cholesterol, and hydrophilic poly(ethylene glycol) respectively. The surface charge of the three different nanoparticles was also modulated by coating the surface with serum albumin. We found that positively charged fluorine-containing particles with lipophobic properties based on a mixture of positively charged polymeric AMD3100 CXCR4 antagonist (PAMD) and PAMD modified with TFTA (mPAMD-TFTA)/siRNA displayed the best cell uptake and transfection efficacy in vitro. Biodistribution evaluation of the nanoparticles in a syngeneic orthotopic PDAC model revealed that the fluorine-containing formulation also achieved the highest PDAC tumor accumulation after IP administration. With a combination of CXCR4 inhibition by PAMD and PLK1 downregulation by siRNA, the treatment with mPAMD-TFTA/siPLK1 showed significant inhibition of both primary and metastatic PDAC tumors. Overall, our study provides insights into and guides the design of the nanoparticles for improved IP delivery of siRNA in PDAC.
- 650 _2
- $a nádorové buněčné linie $7 D045744
- 650 12
- $a halogenace $7 D054879
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a nádory slinivky břišní $x farmakoterapie $7 D010190
- 650 _2
- $a polyelektrolyty $7 D000071228
- 650 _2
- $a malá interferující RNA $7 D034741
- 650 _2
- $a tkáňová distribuce $7 D014018
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Extramural $7 D052061
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Tang, Siyuan $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Tang, Weimin $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Větvička, David $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA; Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Zhang, Chuhan $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Xie, Ying $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Yu, Fei $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Yu, Ao $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Sil, Diptesh $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Li, Jing $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Singh, Rakesh K $u Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- 700 1_
- $a Oupický, David $u Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: david.oupicky@unmc.edu
- 773 0_
- $w MED00002621 $t Journal of controlled release : official journal of the Controlled Release Society $x 1873-4995 $g Roč. 333, č. - (2021), s. 139-150
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/33774121 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20211013 $b ABA008
- 991 __
- $a 20211026133547 $b ABA008
- 999 __
- $a ok $b bmc $g 1714676 $s 1146254
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2021 $b 333 $c - $d 139-150 $e 20210325 $i 1873-4995 $m Journal of controlled release $n J Controlled Release $x MED00002621
- GRA __
- $a R01 CA228524 $p NCI NIH HHS $2 United States
- GRA __
- $a R01 CA235863 $p NCI NIH HHS $2 United States
- LZP __
- $a Pubmed-20211013
