Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics

Nanocarriers encapsulating nucleic acids or protein therapeutics are important tools for modulating biodistribution and enhancing intracellular delivery of biologics. We have recently developed inverse Flash NanoPrecipitation (iFNP), demonstrating its effectiveness in encapsulating biologics at high...

Full description

Bibliographic Details
Main Authors: Chester Markwalter, Leon Wang, Ola Sharaf, Prashanth Padakanti, Mark Esposito, Brian Wilson, Eric Blankemeyer, Sean Carlin, Abass Alavi, Robert K. Prud'homme
Format: Article
Language:English
Published: Andover House Inc. 2022-12-01
Series:Precision Nanomedicine
Online Access:https://precisionnanomedicine.com/article/57619-polymeric-nanocarriers-co-encapsulating-pet-probes-and-protein-therapeutics
_version_ 1798006886864257024
author Chester Markwalter
Leon Wang
Ola Sharaf
Prashanth Padakanti
Mark Esposito
Brian Wilson
Eric Blankemeyer
Sean Carlin
Abass Alavi
Robert K. Prud'homme
author_facet Chester Markwalter
Leon Wang
Ola Sharaf
Prashanth Padakanti
Mark Esposito
Brian Wilson
Eric Blankemeyer
Sean Carlin
Abass Alavi
Robert K. Prud'homme
author_sort Chester Markwalter
collection DOAJ
description Nanocarriers encapsulating nucleic acids or protein therapeutics are important tools for modulating biodistribution and enhancing intracellular delivery of biologics. We have recently developed inverse Flash NanoPrecipitation (iFNP), demonstrating its effectiveness in encapsulating biologics at high loadings and encapsulation efficiency. Here, we present the biodistribution of two iFNP nanocarriers using 64Cu positron emission tomography imaging in a murine adenocarcinoma xenograft model characterized by elevated macrophage content. Two nanocarriers with similar sizes and surfaces were prepared. iFNP produces core-shell-corona nanocarriers where the hydrophobic shell layer in one case was poly(lactic acid) (PLA), and the other nanocarrier shell was poly(styrene) (PS). While the expectation was that the biodistribution and clearance of both nanocarriers would be similar, it was found that the clearance of the PS nanocarrier oc-curred in less than 3 hours while the PLA nanocarrier exhibited sustained circulation times. The mechanism of nanocarrier instability for the PS shell nanocarrier manifests as the development of a negative surface charge due to the exposure of the anionic nanocarrier inner core. The stable PLA-based formulation exhibited circulation times greater than 24 hours and enhanced accumu-lation in the lymphatics and the tumor relative to the unstable formulation. The novel mecha-nism of encapsulation by iFNP motivates the fundamental studies on nanoparticle biodistribu-tion reported here.
first_indexed 2024-04-11T13:01:32Z
format Article
id doaj.art-590de6680bf241d796ca6122cfa61f91
institution Directory Open Access Journal
issn 2639-9431
language English
last_indexed 2024-04-11T13:01:32Z
publishDate 2022-12-01
publisher Andover House Inc.
record_format Article
series Precision Nanomedicine
spelling doaj.art-590de6680bf241d796ca6122cfa61f912022-12-22T04:22:55ZengAndover House Inc.Precision Nanomedicine2639-94312022-12-01Polymeric nanocarriers co-encapsulating PET probes and protein therapeuticsChester MarkwalterLeon WangOla SharafPrashanth PadakantiMark EspositoBrian WilsonEric BlankemeyerSean CarlinAbass AlaviRobert K. Prud'hommeNanocarriers encapsulating nucleic acids or protein therapeutics are important tools for modulating biodistribution and enhancing intracellular delivery of biologics. We have recently developed inverse Flash NanoPrecipitation (iFNP), demonstrating its effectiveness in encapsulating biologics at high loadings and encapsulation efficiency. Here, we present the biodistribution of two iFNP nanocarriers using 64Cu positron emission tomography imaging in a murine adenocarcinoma xenograft model characterized by elevated macrophage content. Two nanocarriers with similar sizes and surfaces were prepared. iFNP produces core-shell-corona nanocarriers where the hydrophobic shell layer in one case was poly(lactic acid) (PLA), and the other nanocarrier shell was poly(styrene) (PS). While the expectation was that the biodistribution and clearance of both nanocarriers would be similar, it was found that the clearance of the PS nanocarrier oc-curred in less than 3 hours while the PLA nanocarrier exhibited sustained circulation times. The mechanism of nanocarrier instability for the PS shell nanocarrier manifests as the development of a negative surface charge due to the exposure of the anionic nanocarrier inner core. The stable PLA-based formulation exhibited circulation times greater than 24 hours and enhanced accumu-lation in the lymphatics and the tumor relative to the unstable formulation. The novel mecha-nism of encapsulation by iFNP motivates the fundamental studies on nanoparticle biodistribu-tion reported here.https://precisionnanomedicine.com/article/57619-polymeric-nanocarriers-co-encapsulating-pet-probes-and-protein-therapeutics
spellingShingle Chester Markwalter
Leon Wang
Ola Sharaf
Prashanth Padakanti
Mark Esposito
Brian Wilson
Eric Blankemeyer
Sean Carlin
Abass Alavi
Robert K. Prud'homme
Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
Precision Nanomedicine
title Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
title_full Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
title_fullStr Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
title_full_unstemmed Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
title_short Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics
title_sort polymeric nanocarriers co encapsulating pet probes and protein therapeutics
url https://precisionnanomedicine.com/article/57619-polymeric-nanocarriers-co-encapsulating-pet-probes-and-protein-therapeutics
work_keys_str_mv AT chestermarkwalter polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT leonwang polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT olasharaf polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT prashanthpadakanti polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT markesposito polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT brianwilson polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT ericblankemeyer polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT seancarlin polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT abassalavi polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics
AT robertkprudhomme polymericnanocarrierscoencapsulatingpetprobesandproteintherapeutics