Patrick A. J. M. de Jongh

Bio: Patrick A. J. M. de Jongh is an academic researcher from University of Warwick. The author has contributed to research in topics: Polymer & Polymerization. The author has an hindex of 8, co-authored 13 publications receiving 146 citations.

Dual Stimuli-Responsive Comb Polymers from Modular N-Acylated Poly(aminoester)-Based Macromonomers

Abstract: We report the synthesis of dual-responsive N-acylated poly(aminoester) (NPAE)-based comb polymers with varying molecular composition and monomer sequence via a combination of spontaneous zwitterionic copolymerization and redox-initiated reversible addition–fragmentation chain transfer (RRAFT) polymerization. NPAE macromonomers were synthesized from different nucleophilic (MN), for example, 2-ethyl-2-oxazoline (EtOx) or 2-ethyl-2-oxazine (EtOz), and electrophilic monomers (ME), for example, acrylic acid (AA) or 2-carboxyethyl acrylate (CEA), to tune the hydrophilicity and sequence of the systems. The latter was found to influence the thermal properties and stability of the respective comb polymers. Turbidity investigations in aqueous solution revealed a dual-responsive behavior of the comb polymers being responsive to both temperature and pH changes due to ω-carboxylic end groups of the NPAE-based macromonomers. Additional methylene groups in the NPAE backbone rendered the corresponding systems more hydrop...

Carboxylated Cy5-labeled comb polymers passively diffuse the cell membrane and target mitochondria

Abstract: A detailed understanding of the cellular uptake and trafficking of nanomaterials is essential for the design of "smart" intracellular drug delivery vehicles. Typically, cellular interactions can be tailored by endowing materials with specific properties, for example, through the introduction of charges or targeting groups. In this study, water-soluble carboxylated N-acylated poly(amino ester)-based comb polymers of different degree of polymerization and side-chain modification were synthesized via a combination of spontaneous zwitterionic copolymerization and redox-initiated reversible addition-fragmentation chain-transfer polymerization and fully characterized by 1H NMR spectroscopy and size exclusion chromatography. The comb polymers showed no cell toxicity against NIH/3T3 and N27 cell lines nor hemolysis. Detailed cellular association and uptake studies by flow cytometry and confocal laser scanning microscopy (CLSM) revealed that the carboxylated polymers were capable of passively diffusing cell membranes and targeting mitochondria. The interplay of pendant carboxylic acids of the comb polymers and the Cy5-label was identified as major driving force for this behavior, which was demonstrated to be applicable in NIH/3T3 and N27 cell lines. Blocking of the carboxylic acids through modification with 2-methoxyethylamine and poly(2-ethyl-2-oxazoline) or replacement of the dye label with a different dye (e.g., fluorescein) resulted in an alteration of the cellular uptake mechanism toward endocytosis as demonstrated by CLSM. In contrast, partial modification of the carboxylic acid groups allowed to retain the cellular interaction, hence, rendering these comb polymers a highly functional mitochondria targeted carrier platform for future drug delivery applications and imaging purposes.

Functional Brush Poly(2-ethyl-2-oxazine)s: Synthesis by CROP and RAFT, Thermoresponsiveness and Grafting onto Iron Oxide Nanoparticles.

Abstract: Brush polymers are highly functional polymeric materials combining the properties of different polymer classes and have found numerous applications, for example, in nanomedicine. Here, the synthesis of functional phosphonate-ester-bearing brush polymers based on poly(2-oxazine)s is reported through a combination of cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazine and reversible addition-fragmentation chain transfer (RAFT) polymerization. In this way, a small library of well-defined (Đ ≤ 1.17) poly(oligo(2-ethyl-2-oxazine) methacrylate) P(OEtOzMA)n brushes with tunable lower critical solution temperature (LCST) behavior and negligible cell toxicity is prepared. Upon deprotection, the phosphonic acid end-group of the P(OEtOzMA)n brush enables the successful grafting-onto iron oxide nanoparticles (IONPs). Colloidal stability of the particle suspension in combination with suitable magnetic resonance imaging (MRI) relaxivities demonstrates the potential of these particles for future applications as negative MRI contrast agents.

50th Anniversary Perspective: RAFT Polymerization—A User Guide

Abstract: This Perspective summarizes the features and limitations of reversible addition–fragmentation chain transfer (RAFT) polymerization, highlighting its strengths and weaknesses, as our understanding of the process, from both a mechanistic and an application point of view, has matured over the past 20 years. It is aimed at both experts in the field and newcomers, including undergraduate and postgraduate students, as well as nonexperts in polymerization who are interested in developing their own polymeric structures by exploiting the simple setup of a RAFT polymerization.

Biomedical applications of biodegradable polymers

Abstract: Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. To fit functional demand, materials with desired physical, chemical, biological, biomechanical, and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications.

Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis.

Abstract: In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers.

Mass spectrometry in polymer chemistry: A state-of-the-art up-date

Abstract: Two decades after the introduction of matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), soft ionization mass spectrometry represents a powerful toolset for the structural investigation of synthetic polymers. The present review highlights the current state-of-the-art, covering the latest developments of novel techniques, enabling instrumentation as well as the important applications of soft ionization MS from the beginning of 2008. Special attention is paid to the role that soft ionization MS has played in the mechanistic investigation of radical polymerization processes since 2005. © 2010 The Royal Society of Chemistry.

Multi-functionalized sequence-defined oligomers from a single building block

Abstract: Two decades of progress in the field of living and controlled polymerizations, combined with the elaboration of efficient conjugation reactions, greatly contributed to the elegant preparation of functionalized macromolecular architectures. However, these state-of-the-art methodologies, while providing a high degree of structural and topological control, are inadequate tools for controlling the polymer microstructure. Crucial parameters like primary structure (i.e. monomer sequence) and tacticity largely remain unmastered by current man-made approaches. Expectations for the next generation synthetic polymers include their performance as single chains, ability to fold and self-regulate, and to sense specific molecules and/or catalyze reactions. These precisely functionalized linear polymers should exhibit sharply defined and tailored structure-activity relationships, analogous to Nature’s delicately engineered macromolecules. Therefore, progress towards reliable sequence-controlled polymerization, enabling preprogrammed distribution of multiple functional groups along the backbone, is drawing attention in a growing number of research groups worldwide. Pioneering efforts to control the primary structure of functionalized polymers have been based on several approaches, such as different reactivity ratios of vinyl monomers, spatial prearrangement of monomers on a (macromolecular) template or, as recently demonstrated, the action of a small-molecule machine. Other attempts use (automated) sequential addition of building blocks on a solid or liquid support, leading to sequence control as a result of iterative coupling steps, thereby omitting the need for pre-organization. These protocols, established for peptide and oligonucleotide synthesis, present considerable drawbacks for sequence-controlled polymerization: they generally require the use of protecting groups and the restricted number of readily available building blocks (‘monomer alphabet’) equipped with the appropriate functional handle can further hamper the preparation of tailor-made functionalized sequences. The development of new chemical protocols for chain elongation, often on a solid support, resulting in sequence-defined (macro)molecular structures with unique backbones and side chain functionalities, or fragments thereof that could be combined to obtain sequence controlled polymers, is therefore highly desirable. We here report on a new coupling strategy for the controlled generation of sequence-defined multi-functionalized oligomers on solid support in a protecting group-free approach, inspired by the ‘submonomer’ synthetic protocol for the preparation of functionalized peptoids, via thiolactone-based chemistry. While the generated oligomers are small in size, reconstitution approaches could further allow the synthesis of larger chains, featuring designed and repetitive display of carefully selected and well-positioned functional entities.