A Rationally Optimized Nanoparticle System for the Delivery of RNA Interference Therapeutics into Pancreatic Tumors in Vivo

Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemic...

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Published inBiomacromolecules Vol. 17; no. 7; pp. 2337 - 2351
Main Authors Teo, Joann, McCarroll, Joshua A, Boyer, Cyrille, Youkhana, Janet, Sagnella, Sharon M, Duong, Hien T. T, Liu, Jie, Sharbeen, George, Goldstein, David, Davis, Thomas P, Kavallaris, Maria, Phillips, Phoebe A
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 11.07.2016
Subjects
Animals
Cell Survival - drug effects
Drug Delivery Systems
Humans
Methacrylates - chemistry
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Nylons - chemistry
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Polymers - chemistry
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Tubulin - chemistry
Tubulin - genetics
Tubulin - metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Abstract Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition–fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly­(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly­[oligo­(ethylene glycol) methyl ether methacrylate] (POEGMA). We showed that star-POEGMA polymers could readily self-assemble with siRNA to form nanoparticles. The star-POEGMA polymers were nontoxic to normal cells and delivered siRNA with high efficiency to pancreatic cancer cells to silence a gene (TUBB3/βIII-tubulin) which is currently undruggable using chemical agents, and is involved in regulating tumor growth and metastases. Notably, systemic administration of star-POEGMA-siRNA resulted in high accumulation of siRNA to orthotopic pancreatic tumors in mice and silenced βIII-tubulin expression by 80% at the gene and protein levels in pancreatic tumors. Together, these novel findings provide strong rationale for the use of star-POEGMA polymers as delivery vehicles for siRNA to pancreatic tumors.
AbstractList Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition-fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA). We showed that star-POEGMA polymers could readily self-assemble with siRNA to form nanoparticles. The star-POEGMA polymers were nontoxic to normal cells and delivered siRNA with high efficiency to pancreatic cancer cells to silence a gene (TUBB3/βIII-tubulin) which is currently undruggable using chemical agents, and is involved in regulating tumor growth and metastases. Notably, systemic administration of star-POEGMA-siRNA resulted in high accumulation of siRNA to orthotopic pancreatic tumors in mice and silenced βIII-tubulin expression by 80% at the gene and protein levels in pancreatic tumors. Together, these novel findings provide strong rationale for the use of star-POEGMA polymers as delivery vehicles for siRNA to pancreatic tumors.
Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition–fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly­(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly­[oligo­(ethylene glycol) methyl ether methacrylate] (POEGMA). We showed that star-POEGMA polymers could readily self-assemble with siRNA to form nanoparticles. The star-POEGMA polymers were nontoxic to normal cells and delivered siRNA with high efficiency to pancreatic cancer cells to silence a gene (TUBB3/βIII-tubulin) which is currently undruggable using chemical agents, and is involved in regulating tumor growth and metastases. Notably, systemic administration of star-POEGMA-siRNA resulted in high accumulation of siRNA to orthotopic pancreatic tumors in mice and silenced βIII-tubulin expression by 80% at the gene and protein levels in pancreatic tumors. Together, these novel findings provide strong rationale for the use of star-POEGMA polymers as delivery vehicles for siRNA to pancreatic tumors.
Author Liu, Jie
Sharbeen, George
Youkhana, Janet
Davis, Thomas P
Teo, Joann
McCarroll, Joshua A
Duong, Hien T. T
Phillips, Phoebe A
Boyer, Cyrille
Goldstein, David
Kavallaris, Maria
Sagnella, Sharon M
AuthorAffiliation Centre for Advanced Macromolecular Design, School of Chemical Engineering
Department of Chemistry
UNSW Australia
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences
Monash University
Australian Centre for NanoMedicine
Prince of Wales Clinical School
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
Tumour Biology and Targeting Program, Children’s Cancer Institute, Lowy Cancer Research Centre
Prince of Wales Hospital
University of Warwick
Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School
AuthorAffiliation_xml – name: UNSW Australia
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– name: Department of Chemistry
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– name: University of Warwick
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– name: Monash University
– name: Prince of Wales Hospital
– name: Australian Centre for NanoMedicine
– name: Tumour Biology and Targeting Program, Children’s Cancer Institute, Lowy Cancer Research Centre
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– name: Centre for Advanced Macromolecular Design, School of Chemical Engineering
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  surname: Teo
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Cites_doi 10.1038/nnano.2011.166
10.1002/asia.201300262
10.1142/S179398441241005X
10.1517/17425247.5.4.371
10.1073/pnas.1309566110
10.1021/nl803487r
10.1038/nrc3180
10.1248/bpb.b13-00059
10.3389/fonc.2014.00153
10.1158/2159-8290.CD-12-0429
10.1016/j.progpolymsci.2015.02.002
10.1038/nrm2085
10.1038/mt.2013.32
10.18632/oncotarget.2664
10.1038/nbt.2614
10.1021/ar800075n
10.3389/fphys.2014.00002
10.1016/S0002-9440(10)64800-6
10.1038/nbt.2612
10.1021/bm1014014
10.1016/j.ymthe.2005.02.010
10.1073/pnas.1411393111
10.1016/j.jconrel.2011.09.093
10.1016/j.canlet.2011.05.002
10.1021/ma0018087
10.3390/molecules200713313
10.1038/nrd2614
10.1021/bm4003199
10.1056/NEJMra0901557
10.1021/ma300410v
10.1016/j.ejpb.2007.09.002
10.1016/j.jconrel.2012.03.015
10.1056/NEJMoa1208760
10.1016/j.nano.2012.05.002
10.18632/oncotarget.2946
10.1158/0008-5472.CAN-07-2477
10.1021/mp400049e
10.1021/bm2006455
10.1042/BJ20080474
10.1038/mt.2011.263
10.1021/ml400082b
10.1158/0008-5472.CAN-07-1077
10.1111/j.1365-2559.2007.02792.x
10.1021/bm800797j
10.1021/bm401526d
10.1021/bm500422v
10.1517/17425247.2014.877442
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References ref9/cit9
ref45/cit45
ref6/cit6
ref36/cit36
ref3/cit3
ref27/cit27
ref18/cit18
ref11/cit11
ref25/cit25
ref16/cit16
ref29/cit29
ref32/cit32
ref23/cit23
ref39/cit39
ref14/cit14
ref8/cit8
ref5/cit5
ref31/cit31
ref2/cit2
ref43/cit43
ref34/cit34
ref37/cit37
ref28/cit28
ref40/cit40
ref20/cit20
ref17/cit17
ref10/cit10
ref26/cit26
ref35/cit35
ref19/cit19
ref21/cit21
ref12/cit12
ref15/cit15
ref42/cit42
ref46/cit46
ref41/cit41
ref22/cit22
ref13/cit13
ref33/cit33
ref4/cit4
ref30/cit30
ref47/cit47
ref1/cit1
ref24/cit24
ref38/cit38
ref44/cit44
ref7/cit7
References_xml – ident: ref33/cit33
  doi: 10.1038/nnano.2011.166
– ident: ref32/cit32
  doi: 10.1002/asia.201300262
– ident: ref41/cit41
  doi: 10.1142/S179398441241005X
– ident: ref21/cit21
  doi: 10.1517/17425247.5.4.371
– ident: ref34/cit34
  doi: 10.1073/pnas.1309566110
– ident: ref47/cit47
  doi: 10.1021/nl803487r
– ident: ref19/cit19
  doi: 10.1038/nrc3180
– ident: ref22/cit22
  doi: 10.1248/bpb.b13-00059
– ident: ref6/cit6
  doi: 10.3389/fonc.2014.00153
– ident: ref10/cit10
  doi: 10.1158/2159-8290.CD-12-0429
– ident: ref16/cit16
  doi: 10.1016/j.progpolymsci.2015.02.002
– ident: ref2/cit2
  doi: 10.1038/nrm2085
– ident: ref9/cit9
  doi: 10.1038/mt.2013.32
– ident: ref24/cit24
  doi: 10.18632/oncotarget.2664
– ident: ref44/cit44
  doi: 10.1038/nbt.2614
– ident: ref31/cit31
  doi: 10.1021/ar800075n
– ident: ref3/cit3
  doi: 10.3389/fphys.2014.00002
– ident: ref27/cit27
  doi: 10.1016/S0002-9440(10)64800-6
– ident: ref43/cit43
  doi: 10.1038/nbt.2612
– ident: ref15/cit15
  doi: 10.1021/bm1014014
– ident: ref36/cit36
  doi: 10.1016/j.ymthe.2005.02.010
– ident: ref35/cit35
  doi: 10.1073/pnas.1411393111
– ident: ref5/cit5
  doi: 10.1016/j.jconrel.2011.09.093
– ident: ref26/cit26
  doi: 10.1016/j.canlet.2011.05.002
– ident: ref23/cit23
  doi: 10.1021/ma0018087
– ident: ref39/cit39
  doi: 10.3390/molecules200713313
– ident: ref4/cit4
  doi: 10.1038/nrd2614
– ident: ref11/cit11
  doi: 10.1021/bm4003199
– ident: ref1/cit1
  doi: 10.1056/NEJMra0901557
– ident: ref30/cit30
  doi: 10.1021/ma300410v
– ident: ref42/cit42
  doi: 10.1016/j.ejpb.2007.09.002
– ident: ref38/cit38
  doi: 10.1016/j.jconrel.2012.03.015
– ident: ref8/cit8
  doi: 10.1056/NEJMoa1208760
– ident: ref37/cit37
  doi: 10.1016/j.nano.2012.05.002
– ident: ref7/cit7
  doi: 10.18632/oncotarget.2946
– ident: ref46/cit46
  doi: 10.1158/0008-5472.CAN-07-2477
– ident: ref18/cit18
  doi: 10.1021/mp400049e
– ident: ref12/cit12
  doi: 10.1021/bm2006455
– ident: ref40/cit40
  doi: 10.1042/BJ20080474
– ident: ref20/cit20
  doi: 10.1038/mt.2011.263
– ident: ref14/cit14
  doi: 10.1021/ml400082b
– ident: ref25/cit25
  doi: 10.1158/0008-5472.CAN-07-1077
– ident: ref28/cit28
  doi: 10.1111/j.1365-2559.2007.02792.x
– ident: ref17/cit17
  doi: 10.1021/bm800797j
– ident: ref29/cit29
  doi: 10.1021/bm401526d
– ident: ref13/cit13
  doi: 10.1021/bm500422v
– ident: ref45/cit45
  doi: 10.1517/17425247.2014.877442
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Snippet Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer....
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SubjectTerms Animals
Cell Survival - drug effects
Drug Delivery Systems
Humans
Methacrylates - chemistry
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Nylons - chemistry
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Polymers - chemistry
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Tubulin - chemistry
Tubulin - genetics
Tubulin - metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Title A Rationally Optimized Nanoparticle System for the Delivery of RNA Interference Therapeutics into Pancreatic Tumors in Vivo
URI http://dx.doi.org/10.1021/acs.biomac.6b00185
https://www.ncbi.nlm.nih.gov/pubmed/27305597
Volume 17
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