4PD functionalized dendrimers: A flexible tool for in vivo gene silencing of tumor-educated myeloid cells

Serena Zilio, Jennifer L. Vella, Adriana C. De La Fuente, Pirouz M. Daftarian, Donald Weed, Angel Kaifer, Ilaria Marigo, Kevin Leone, Vincenzo Bronte, Paolo Serafini

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways. In this article, we describe the 4PD nanoplatform, which allows the in vivo preferential transfection and in vivo tracking of TEMCs with the desired RNAs. This platform is based on the conjugation of CD124/IL-4Ra-targeting peptide with G5 PAMAM dendrimers as the loading surface and can convey therapeutic or experimental RNAs of interest. When injected i.v. in mice bearing CT26 colon carcinoma or B16 melanoma, the 4PD nanoparticles predominantly accumulate at the tumor site, transfecting intratumoral myeloid cells. The use of 4PD to deliver a combination of STAT3- and C/EBPb-specific short hairpin RNA or miR-142-3p confirmed the importance of these genes and microRNAs in TEMC biology and indicates that silencing of both genes is necessary to increase the efficacy of immune interventions. Thus, the 4PD nanoparticle can rapidly and cost effectively modulate and assess the in vivo function of microRNAs and mRNAs in TEMCs.

Original languageEnglish (US)
Pages (from-to)4166-4177
Number of pages12
JournalJournal of Immunology
Volume198
Issue number10
DOIs
StatePublished - May 15 2017

Fingerprint

Dendrimers
Gene Silencing
Myeloid Cells
Neoplasms
MicroRNAs
Nanoparticles
RNA
Gene Knockout Techniques
Experimental Melanomas
Small Interfering RNA
Transfection
Cell Biology
Colon
Neoplasm Metastasis
Technology
Carcinoma
Costs and Cost Analysis
Messenger RNA
Peptides
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

4PD functionalized dendrimers : A flexible tool for in vivo gene silencing of tumor-educated myeloid cells. / Zilio, Serena; Vella, Jennifer L.; De La Fuente, Adriana C.; Daftarian, Pirouz M.; Weed, Donald; Kaifer, Angel; Marigo, Ilaria; Leone, Kevin; Bronte, Vincenzo; Serafini, Paolo.

In: Journal of Immunology, Vol. 198, No. 10, 15.05.2017, p. 4166-4177.

Research output: Contribution to journalArticle

Zilio, Serena ; Vella, Jennifer L. ; De La Fuente, Adriana C. ; Daftarian, Pirouz M. ; Weed, Donald ; Kaifer, Angel ; Marigo, Ilaria ; Leone, Kevin ; Bronte, Vincenzo ; Serafini, Paolo. / 4PD functionalized dendrimers : A flexible tool for in vivo gene silencing of tumor-educated myeloid cells. In: Journal of Immunology. 2017 ; Vol. 198, No. 10. pp. 4166-4177.
@article{ef9acb90b0da4bd2aebf030370ae0b7b,
title = "4PD functionalized dendrimers: A flexible tool for in vivo gene silencing of tumor-educated myeloid cells",
abstract = "Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways. In this article, we describe the 4PD nanoplatform, which allows the in vivo preferential transfection and in vivo tracking of TEMCs with the desired RNAs. This platform is based on the conjugation of CD124/IL-4Ra-targeting peptide with G5 PAMAM dendrimers as the loading surface and can convey therapeutic or experimental RNAs of interest. When injected i.v. in mice bearing CT26 colon carcinoma or B16 melanoma, the 4PD nanoparticles predominantly accumulate at the tumor site, transfecting intratumoral myeloid cells. The use of 4PD to deliver a combination of STAT3- and C/EBPb-specific short hairpin RNA or miR-142-3p confirmed the importance of these genes and microRNAs in TEMC biology and indicates that silencing of both genes is necessary to increase the efficacy of immune interventions. Thus, the 4PD nanoparticle can rapidly and cost effectively modulate and assess the in vivo function of microRNAs and mRNAs in TEMCs.",
author = "Serena Zilio and Vella, {Jennifer L.} and {De La Fuente}, {Adriana C.} and Daftarian, {Pirouz M.} and Donald Weed and Angel Kaifer and Ilaria Marigo and Kevin Leone and Vincenzo Bronte and Paolo Serafini",
year = "2017",
month = "5",
day = "15",
doi = "10.4049/jimmunol.1600833",
language = "English (US)",
volume = "198",
pages = "4166--4177",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - 4PD functionalized dendrimers

T2 - A flexible tool for in vivo gene silencing of tumor-educated myeloid cells

AU - Zilio, Serena

AU - Vella, Jennifer L.

AU - De La Fuente, Adriana C.

AU - Daftarian, Pirouz M.

AU - Weed, Donald

AU - Kaifer, Angel

AU - Marigo, Ilaria

AU - Leone, Kevin

AU - Bronte, Vincenzo

AU - Serafini, Paolo

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways. In this article, we describe the 4PD nanoplatform, which allows the in vivo preferential transfection and in vivo tracking of TEMCs with the desired RNAs. This platform is based on the conjugation of CD124/IL-4Ra-targeting peptide with G5 PAMAM dendrimers as the loading surface and can convey therapeutic or experimental RNAs of interest. When injected i.v. in mice bearing CT26 colon carcinoma or B16 melanoma, the 4PD nanoparticles predominantly accumulate at the tumor site, transfecting intratumoral myeloid cells. The use of 4PD to deliver a combination of STAT3- and C/EBPb-specific short hairpin RNA or miR-142-3p confirmed the importance of these genes and microRNAs in TEMC biology and indicates that silencing of both genes is necessary to increase the efficacy of immune interventions. Thus, the 4PD nanoparticle can rapidly and cost effectively modulate and assess the in vivo function of microRNAs and mRNAs in TEMCs.

AB - Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways. In this article, we describe the 4PD nanoplatform, which allows the in vivo preferential transfection and in vivo tracking of TEMCs with the desired RNAs. This platform is based on the conjugation of CD124/IL-4Ra-targeting peptide with G5 PAMAM dendrimers as the loading surface and can convey therapeutic or experimental RNAs of interest. When injected i.v. in mice bearing CT26 colon carcinoma or B16 melanoma, the 4PD nanoparticles predominantly accumulate at the tumor site, transfecting intratumoral myeloid cells. The use of 4PD to deliver a combination of STAT3- and C/EBPb-specific short hairpin RNA or miR-142-3p confirmed the importance of these genes and microRNAs in TEMC biology and indicates that silencing of both genes is necessary to increase the efficacy of immune interventions. Thus, the 4PD nanoparticle can rapidly and cost effectively modulate and assess the in vivo function of microRNAs and mRNAs in TEMCs.

UR - http://www.scopus.com/inward/record.url?scp=85019670042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019670042&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1600833

DO - 10.4049/jimmunol.1600833

M3 - Article

C2 - 28396317

AN - SCOPUS:85019670042

VL - 198

SP - 4166

EP - 4177

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -