TY - JOUR
T1 - Novel Core–Shell Polyamine Phosphate Nanoparticles Self-Assembled from PEGylated Poly(allylamine hydrochloride) with Low Toxicity and Increased In Vivo Circulation Time
AU - Andreozzi, Patrizia
AU - Simó, Cristina
AU - Moretti, Paolo
AU - Porcel, Joaquin Martinez
AU - Lüdtke, Tanja Ursula
AU - Ramirez, Maria de los Angeles
AU - Tamberi, Lorenza
AU - Marradi, Marco
AU - Amenitsch, Heinz
AU - Llop, Jordi
AU - Ortore, Maria Grazia
AU - Moya, Sergio Enrique
N1 - Funding Information:
The authors thank Elettra Synchrotron for beamtime allocation. The authors acknowledge the CERIC‐ERIC Consortium for the access to experimental facilities. The authors thank Multimodal 3D for 3D image analysis. The authors also thank Dr. Richard Murry for correcting the manuscript. S.E.M. and J.L. thank the MAT2017‐88752‐R and CTQ2017‐87637‐R Retos projects, respectively, from the Ministerio de Economía, Industria y Competitividad, Gobierno de España. This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency—Grant No. MDM‐2017‐0720.
Funding Information:
The authors thank Elettra?Synchrotron?for beamtime allocation. The authors acknowledge the CERIC-ERIC Consortium for the access to experimental facilities. The authors thank Multimodal 3D for 3D image analysis. The authors also thank Dr. Richard Murry for correcting the manuscript. S.E.M. and J.L. thank the MAT2017-88752-R and CTQ2017-87637-R Retos projects, respectively, from the Ministerio de Econom?a, Industria y Competitividad, Gobierno de Espa?a. This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency?Grant No. MDM-2017-0720.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/9/2
Y1 - 2021/9/2
N2 - An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico-chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X-ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of 18F labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non-PEGylated ones.
AB - An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico-chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X-ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of 18F labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non-PEGylated ones.
KW - biological fate
KW - polyamine phosphate nanoparticles
KW - polyethylene glycol
KW - self assembly
KW - small angle X-ray scattering
UR - http://www.scopus.com/inward/record.url?scp=85110515295&partnerID=8YFLogxK
U2 - 10.1002/smll.202102211
DO - 10.1002/smll.202102211
M3 - Article
C2 - 34278713
AN - SCOPUS:85110515295
SN - 1613-6810
VL - 17
JO - Small
JF - Small
IS - 35
M1 - 2102211
ER -