Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle

The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delive...

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Veröffentlicht in:Biomacromolecules 2024-06, Vol.25 (6), p.3360-3372
Hauptverfasser: Bao, Qingming, Bao, Mingming, Xiao, Hai, Ganbold, Tsogzolmaa, Han, Shuqin, Baigude, Huricha
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container_end_page 3372
container_issue 6
container_start_page 3360
container_title Biomacromolecules
container_volume 25
creator Bao, Qingming
Bao, Mingming
Xiao, Hai
Ganbold, Tsogzolmaa
Han, Shuqin
Baigude, Huricha
description The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.
doi_str_mv 10.1021/acs.biomac.4c00025
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identifier ISSN: 1525-7797
ispartof Biomacromolecules, 2024-06, Vol.25 (6), p.3360-3372
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source MEDLINE; ACS Publications
subjects adenosine
Animals
beta-Glucans - chemistry
beta-Glucans - pharmacology
Cell Line, Tumor
curdlan
cytokines
Drug Delivery Systems - methods
endocytosis
Ligands
lungs
macrophages
Macrophages - drug effects
Macrophages - metabolism
mannose
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
metastasis
Mice
Mice, Inbred C57BL
nanoparticles
Nanoparticles - chemistry
neoplasms
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - pharmacology
oligonucleotides
polymers
RNA
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - chemistry
RNA, Small Interfering - pharmacology
synergism
therapeutics
Tumor-Associated Macrophages - drug effects
title Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle
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