Folate-PEG Conjugates of a Far-Red Light-Activatable Paclitaxel Prodrug to Improve Selectivity toward Folate Receptor-Positive Cancer Cells

ACS Omega
Pritam ThapaYoungjae You

Abstract

We recently demonstrated the far-red light-activatable prodrug of paclitaxel (PTX), Pc-(L-PTX)2. Upon illumination with a 690 nm laser, Pc-(L-PTX)2 showed combinational cell killing from rapid photodynamic therapy damage by singlet oxygen, followed by sustained chemotherapy effects from locally released PTX. However, its high lipophilicity (log D7.4 > 3.1) caused aggregation in aqueous solutions and has nonselectivity toward cancer cells. To solve these important problems, we prepared folic acid (FA)-conjugated and photoactivatable prodrugs of PTX with a polyethylene glycol (PEG) spacer of various chain lengths: FA-PEG n -Pc-L-PTX [n = 0 (0k, 5), ∼23 (1k, 7a), ∼45 (2k, 7b), ∼80 (3.5k, 7c), or ∼114 (5k, 7d)]. The PEGylated prodrugs 7a-d had a much improved hydrophilicity compared with the non-PEGylated prodrug, Pc-(L-PTX)2. As the PEG length increased, the hydrophilicity of the prodrug increased (log D7.4 values: 1.28, 0.09, -0.24, and -0.59 for 1k, 2k, 3.5k, and 5k PEG prodrugs, respectively). Fluorescence spectral data suggested that the PEGylated prodrugs had good solubility in the culture medium at lower concentrations (<1-2 μM), but showed fluorescence quenching due to limited solubility at higher concentrations (>2 μM). Dy...Continue Reading

References

Mar 18, 1994·Science·R GrefR Langer
Jan 1, 1996·Annual Review of Nutrition·A C Antony
Jun 24, 1998·Journal of the National Cancer Institute·T J DoughertyQ Peng
Sep 19, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·S Wang, P S Low
Aug 21, 2001·Clinical Pharmacokinetics·J M HarrisM Modi
Sep 3, 2002·Advanced Drug Delivery Reviews·Yingjuan Lu, Philip S Low
Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
May 2, 2003·Nature Reviews. Cancer·Dennis E J G J DolmansRakesh K Jain
Apr 20, 2004·Advanced Drug Delivery Reviews·Philip S Low, Asok C Antony
Mar 16, 2006·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Peter K Kaiser, UNKNOWN Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group
Jul 21, 2006·The Journal of Physical Chemistry. B·Esben SkovsenPeter R Ogilby
Aug 12, 2006·Bioorganic & Medicinal Chemistry Letters·Walter A HennePhilip S Low
Jan 17, 2007·Lasers in Medical Science·Michael H Gold
Mar 19, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gianfranco PasutOddone Schiavon
Mar 17, 2010·International Journal of Pharmaceutics·Fabienne DanhierVéronique Préat
Apr 29, 2010·Chemical Communications : Chem Comm·Xiong-Jie JiangDennis K P Ng
May 17, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Michael D'AngelicaJinru Shia
May 28, 2011·CA: a Cancer Journal for Clinicians·Patrizia AgostinisJakub Golab
Sep 29, 2011·International Journal of Pharmaceutics·Yanhua LiuZhonggui He
Jun 6, 2012·Expert Opinion on Drug Delivery·Lesheng TengRobert J Lee
Sep 18, 2012·Journal of Biomaterials Applications·Linlin ZhaoSo Yeon Kim
Dec 15, 2012·Nano Reviews·Grant L ZwickeConstance J Jeffery
Dec 18, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Daniel C ChristophFred R Hirsch
Feb 21, 2013·Clinical Endoscopy·Ron R Allison, Keyvan Moghissi
Jan 10, 2013·ACS Medicinal Chemistry Letters·Abugafar M L HossionYoungjae You
Aug 12, 2014·Nature Reviews. Drug Discovery·Samir MitragotriRobert Langer
Mar 31, 2015·PloS One·Brian M NecelaEdith A Perez
Jun 13, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J A LedermannT Thigpen
Dec 10, 2015·Annals of the American Thoracic Society·Gal ShafirsteinChukwumere E Nwogu

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Citations

Apr 1, 2018·Chemistry : a European Journal·André Luiz TessaroSalvatore Sortino
Aug 17, 2018·Photochemistry and Photobiology·Goutam GhoshAlexander Greer
Dec 29, 2019·Photochemistry and Photobiology·Bharathiraja SubramaniyanYoungjae You
May 13, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Fengrong ZhangHuiyu Liu
Nov 2, 2019·MedChemComm·Jorge Peiró CadahíaMads H Clausen
Jun 10, 2020·Drug Development Research·Prashant S KharkarKhushwant S Yadav
Apr 8, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Qiang LiWei-Hong Zhu
Mar 18, 2021·Pharmaceutical Development and Technology·Afaf H Al-NadafNouf N Mahmoud
Mar 19, 2021·Chemical Society Reviews·Yufei XueNicolas Hans Voelcker
Jul 13, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mengjie LiYoungjae You
Jul 20, 2020·Anti-cancer Agents in Medicinal Chemistry·Shiyu ChenRunliang Feng
Jul 16, 2020·Journal of Medicinal Chemistry·Summer Y Y HaDennis K P Ng
Oct 31, 2020·Chemical Reviews·Roy WeinstainPetr Klán

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Methods Mentioned

BETA
nuclear magnetic resonance
Fluorescence
dynamic light scattering

Software Mentioned

Prism
GraphPad
iNMR

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