eprintid: 10170783
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/17/07/83
datestamp: 2023-05-26 12:18:39
lastmod: 2023-05-26 12:18:39
status_changed: 2023-05-26 12:18:39
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Al-Natour, Mohammad
creators_name: Yousif, Mohamed D
creators_name: Cavanagh, Robert
creators_name: Abouselo, Amjad
creators_name: Apebende, Edward A
creators_name: Ghaemmaghami, Amir M
creators_name: Kim, Dong-Hyun
creators_name: Aylott, Jonathan W
creators_name: Taresco, Vincenzo
creators_name: Chauhan, Veeren M
creators_name: Alexander, Cameron
title: Facile Dye-Initiated Polymerization of Lactide-Glycolide Generates Highly Fluorescent Poly(lactic-co-glycolic Acid) for Enhanced Characterization of Cellular Delivery
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G08
keywords: Science & Technology, Physical Sciences, Polymer Science, PLGA NANOPARTICLES, DRUG-DELIVERY, STABILITY, RELEASE, SYSTEM
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Poly(lactic-co-glycolic acid) (PLGA) is a versatile synthetic copolymer that is widely used in pharmaceutical applications. This is because it is well-tolerated in the body, and copolymers of varying physicochemical properties are readily available via ring-opening polymerization. However, native PLGA polymers are hard to track as drug delivery carriers when delivered to subcellular spaces, due to the absence of an easily accessible "handle" for fluorescent labeling. Here we show a one-step, scalable, solvent-free, synthetic route to fluorescent blue (2-aminoanthracene), green (5-aminofluorescein), and red (rhodamine-6G) PLGA, in which every polymer chain in the sample is fluorescently labeled. The utility of initiator-labeled PLGA was demonstrated through the preparation of nanoparticles, capable of therapeutic subcellular delivery to T-helper-precursor-1 (THP-1) macrophages, a model cell line for determining in vitro biocompatibility and particle uptake. Super resolution confocal fluorescence microscopy imaging showed that dye-initiated PLGA nanoparticles were internalized to punctate regions and retained bright fluorescence over at least 24 h. In comparison, PLGA nanoparticles with 5-aminofluorescein introduced by conventional nanoprecipitation/encapsulation showed diffuse and much lower fluorescence intensity in the same cells and over the same time periods. The utility of this approach for in vitro drug delivery experiments was demonstrated through the concurrent imaging of the fluorescent drug doxorubicin (λex = 480 nm, λem = 590 nm) with carrier 5-aminofluorescein PLGA, also in THP-1 cells, in which the intracellular locations of the drug and the polymer could be clearly visualized. Finally, the dye-labeled particles were evaluated in an in vivo model, via delivery to the nematode Caenorhabditis elegans, with bright fluorescence again apparent in the internal tract after 3 h. The results presented in this manuscript highlight the ease of synthesis of highly fluorescent PLGA, which could be used to augment tracking of future therapeutics and accelerate in vitro and in vivo characterization of delivery systems prior to clinical translation.
date: 2020-03-17
date_type: published
publisher: AMER CHEMICAL SOC
official_url: https://doi.org/10.1021/acsmacrolett.9b01014
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1943351
doi: 10.1021/acsmacrolett.9b01014
medium: Print-Electronic
lyricists_name: Yousif, Mohamed
lyricists_id: MYOUS16
actors_name: Yousif, Mohamed
actors_id: MYOUS16
actors_role: owner
funding_acknowledgements: [University of Petra]; EP/P006485/1 [Engineering and Physical Sciences Research Council]; EP/N03371X/1 [Engineering and Physical Sciences Research Council]; EP/H005625/1 [Engineering and Physical Sciences Research Council]; BB/L013827/1 [Biotechnology and Biological Sciences Research Council]; WM150086 [Royal Society [Wolfson Research Merit Award]]; EP/N009126/1 [Engineering and Physical Sciences Research Council]; BB/L013827/1 [BBSRC]; BB/R012415/1 [BBSRC]; EP/P006485/1 [EPSRC]; EP/N009126/1 [EPSRC]; EP/N03371X/1 [EPSRC]; EP/H005625/1 [EPSRC]
full_text_status: public
publication: ACS Macro Letters
volume: 9
number: 3
pagerange: 431-437
pages: 7
event_location: United States
issn: 2161-1653
citation:        Al-Natour, Mohammad;    Yousif, Mohamed D;    Cavanagh, Robert;    Abouselo, Amjad;    Apebende, Edward A;    Ghaemmaghami, Amir M;    Kim, Dong-Hyun;                 ... Alexander, Cameron; + view all <#>        Al-Natour, Mohammad;  Yousif, Mohamed D;  Cavanagh, Robert;  Abouselo, Amjad;  Apebende, Edward A;  Ghaemmaghami, Amir M;  Kim, Dong-Hyun;  Aylott, Jonathan W;  Taresco, Vincenzo;  Chauhan, Veeren M;  Alexander, Cameron;   - view fewer <#>    (2020)    Facile Dye-Initiated Polymerization of Lactide-Glycolide Generates Highly Fluorescent Poly(lactic-co-glycolic Acid) for Enhanced Characterization of Cellular Delivery.                   ACS Macro Letters , 9  (3)   pp. 431-437.    10.1021/acsmacrolett.9b01014 <https://doi.org/10.1021/acsmacrolett.9b01014>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10170783/1/pub%201.pdf