End-Group Dye-Labeled Poly(hemiacetal ester) Block Copolymers: Enhancing Hydrolytic Stability and Loading Capacity for Micellar (Immuno-)Drug Delivery

被引:3
作者
Bixenmann, Leon [1 ,2 ]
Ahmad, Taufiq [3 ]
Stephan, Fabian [2 ]
Nuhn, Lutz [1 ,2 ]
机构
[1] Julius Maximilians Univ Wurzburg, Inst Funct Mat & Biofabricat, Dept Chem & Pharm, D-97070 Wurzburg, Germany
[2] Max Planck Inst Polymer Res, D-55128 Mainz, Germany
[3] Univ Hosp Wurzburg, Inst Funct Mat & Biofabricat, Dept Funct Mat Med & Dent, D-97070 Wurzburg, Germany
关键词
RING-OPENING POLYMERIZATION; ACYLAL HYDROLYSIS; MECHANISM; POLYMERS; OXIRANES; NANOGELS; ALCOHOLS; KINETICS;
D O I
10.1021/acs.biomac.4c01229
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers' in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly(hemiacetal ester)s for (immuno)drug delivery purposes.
引用
收藏
页码:7958 / 7974
页数:17
相关论文
共 58 条
[21]   KINETICS AND MECHANISM OF THE HYDROLYSIS OF 1-ARYLOXYETHYL ALKANOATES [J].
HALL, CD ;
GOULDING, CW .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1995, (07) :1471-1477
[22]   Kinetics and mechanism of the hydrolysis of tetrahydro-2-furyl and tetrahydropyran-2-yl alkanoates [J].
Hall, CD ;
Le, VT .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1998, (06) :1483-1488
[23]   Enzyme-Responsive Amphiphilic PEG-Dendron Hybrids and Their Assembly into Smart Micellar Nanocarriers [J].
Harnoy, Assaf J. ;
Rosenbaum, Ido ;
Tirosh, Einat ;
Ebenstein, Yuval ;
Shaharabani, Rona ;
Beck, Roy ;
Amir, Roey J. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2014, 136 (21) :7531-7534
[24]   Core Crosslinking of Biodegradable Block Copolymer Micelles Based on Poly(ester carbonate) [J].
Hu, Xiuli ;
Chen, Xuesi ;
Wei, Jizheng ;
Liu, Shi ;
Jing, Xiabin .
MACROMOLECULAR BIOSCIENCE, 2009, 9 (05) :456-463
[25]   Materials engineering for immunomodulation [J].
Hubbell, Jeffrey A. ;
Thomas, Susan N. ;
Swartz, Melody A. .
NATURE, 2009, 462 (7272) :449-460
[26]   Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators [J].
Huppertsberg, Anne ;
Kaps, Leonard ;
Zhong, Zifu ;
Schmitt, Sascha ;
Stickdorn, Judith ;
Deswarte, Kim ;
Combes, Francis ;
Czysch, Christian ;
De Vrieze, Jana ;
Kasmi, Sabah ;
Choteschovsky, Niklas ;
Klefenz, Adrian ;
Medina-Montano, Carolina ;
Winterwerber, Pia ;
Chen, Chaojian ;
Bros, Matthias ;
Lienenklaus, Stefan ;
Sanders, Niek N. ;
Koynov, Kaloian ;
Schuppan, Detlef ;
Lambrecht, Bart N. ;
David, Sunil A. ;
De Geest, Bruno G. ;
Nuhn, Lutz .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2021, 143 (26) :9872-9883
[27]   Cationic Ring-Opening Co- and Terpolymerizations of Lactic Acid-Derived 1,3-Dioxolan-4-ones with Oxiranes and Vinyl Ethers: Nonhomopolymerizable Monomer for Degradable Co- and Terpolymers [J].
Hyoi, Kano ;
Kanazawa, Arihiro ;
Aoshima, Sadahito .
ACS MACRO LETTERS, 2019, 8 (02) :128-133
[28]   Ring-Expansion Living Cationic Polymerization via Reversible Activation of a Hemiacetal Ester Bond [J].
Kammiyada, Hajime ;
Konishi, Akito ;
Ouchi, Makoto ;
Sawamoto, Mitsuo .
ACS MACRO LETTERS, 2013, 2 (06) :531-534
[29]   pH-degradable, bisphosphonate-loaded nanogels attenuate liver fibrosis by repolarization of M2-type macrophages [J].
Kaps, Leonard ;
Huppertsberg, Anne ;
Choteschovsky, Niklas ;
Klefenz, Adrian ;
Durak, Feyza ;
Schroers, Babara ;
Diken, Mustafa ;
Eichler, Emma ;
Rosigkeit, Sebastian ;
Schmitt, Sascha ;
Leps, Christian ;
Schulze, Alicia ;
Foerster, Friedrich ;
Bockamp, Ernesto ;
De Geest, Bruno G. ;
Koynov, Kaloian ;
Raeder, Hans-Joachim ;
Tenzer, Stefan ;
Marini, Federico ;
Schuppan, Detlef ;
Nuhn, Lutz .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2022, 119 (12)
[30]   Post-Polymerization Modifications to Prepare Biomedical Nanocarriers with Varying Internal Structures, their Properties and Impact on Protein Corona Formation [J].
Kockelmann, Johannes ;
Zentel, Rudolf ;
Nuhn, Lutz .
MACROMOLECULAR CHEMISTRY AND PHYSICS, 2023, 224 (24)