The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.

http://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.5b00671

Light-Controlled Radical Polymerization: Mechanisms, Methods, and Applications

Exosomes, a subgroup of extracellular vesicles (EVs), have been recognized as important mediators of long distance intercellular communication and are involved in a diverse range of biological processes. Because of their ideal native structure and characteristics, exosomes are promising nanocarriers for clinical use. Exosomes are engineered at the cellular level under natural conditions, but successful exosome modification requires further exploration. The focus of this paper is to summarize passive and active loading approaches, as well as specific exosome modifications and examples of the delivery of therapeutic and imaging molecules. Examples of exosomes derived from a variety of biological origins are also provided. The biocompatible characteristics of exosomes, with suitable modifications, can increase the stability and efficacy of imaging probes and therapeutics while enhancing cellular uptake. Challenges in clinical translation of exosome-based platforms from different cell sources and the advantages of each are also reviewed and discussed.

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Engineering exosomes as refined biological nanoplatforms for drug delivery.

Recently, polymerization-induced self-assembly (PISA) has become widely recognized as a robust and efficient route to produce block copolymer nanoparticles of controlled size, morphology, and surface chemistry. Several reviews of this field have been published since 2012, but a substantial number of new papers have been published in the last three years. In this Perspective, we provide a critical appraisal of the various advantages offered by this approach, while also pointing out some of its current drawbacks. Promising future research directions as well as remaining technical challenges and unresolved problems are briefly highlighted.

http://pubs.acs.org/doi/pdf/10.1021/acs.macromol.5b02602

A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly.

Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.

/pdf/liposomes-and-polymersomes-a-comparative-review-towards-cell-2fz82kdmcz.pdf

Liposomes and polymersomes: a comparative review towards cell mimicking.

The field of 3D printing is continuing its rapid development in both academic and industrial research environments. The development of 3D printing technologies has opened new implementations in rapid prototyping, tooling, dentistry, microfluidics, biomedical devices, tissue engineering, drug delivery, etc. Among different 3D printing techniques, photopolymerization-based process (such as stereolithography and digital light processing) offers flexibility over the final properties of the 3D printed materials (such as optical, chemical, and mechanical properties) using versatile polymer chemistry. The strategy behind the 3D photopolymerization is based on using monomers/oligomers in liquid state (in the presence of photoinitiators) that can be photopolymerized (via radical or cationic mechanism) upon exposure to light source of different wavelengths (depending on the photoinitiator system). An overview of recent evolutions in the field of photopolymerization-based 3D printing and highlights of novel 3D print...

Photopolymerization in 3D Printing

Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications Cyrille Boyer,*,†,‡ Nathaniel Alan Corrigan,‡ Kenward Jung,‡ Diep Nguyen,‡ Thuy-Khanh Nguyen,‡ Nik Nik M. Adnan,†,‡ Susan Oliver,†,‡ Sivaprakash Shanmugam,‡ and Jonathan Yeow†,‡ †Australian Centre for Nanomedicine, and ‡Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney 2052, Australia

Copper-Mediated Living Radical Polymerization (Atom Transfer Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications

The application of photochemistry to polymer and material science has led to the development of complex yet efficient systems for polymerization, polymer post-functionalization, and advanced materials production. Using light to activate chemical reaction pathways in these systems not only leads to exquisite control over reaction dynamics, but also allows complex synthetic protocols to be easily achieved. Compared to polymerization systems mediated by thermal, chemical, or electrochemical means, photoinduced polymerization systems can potentially offer more versatile methods for macromolecular synthesis. We highlight the utility of light as an energy source for mediating photopolymerization, and present some promising examples of systems which are advancing materials production through their exploitation of photochemistry.

/pdf/seeing-the-light-advancing-materials-chemistry-through-4jb2o1rrgq.pdf

Seeing the Light: Advancing Materials Chemistry through Photopolymerization.

In this Perspective, we summarize recent progress in polymerization-induced self-assembly (PISA) for the rational synthesis of block copolymer nanoparticles with various morphologies. Much of the PISA literature has been based on thermally initiated reversible addition–fragmentation chain transfer (RAFT) polymerization. Herein, we pay particular attention to alternative PISA protocols, which allow the preparation of nanoparticles with improved control over copolymer morphology and functionality. For example, initiation based on visible light, redox chemistry, or enzymes enables the incorporation of sensitive monomers and fragile biomolecules into block copolymer nanoparticles. Furthermore, PISA syntheses and postfunctionalization of the resulting nanoparticles (e.g., cross-linking) can be conducted sequentially without intermediate purification by using various external stimuli. Finally, PISA formulations have been optimized via high-throughput polymerization and recently evaluated within flow reactors for facile scale-up syntheses.

Emerging trends in polymerization-induced self-assembly

Nanoparticle size, surface charge and material composition are known to affect the uptake of nanoparticles by cells. However, whether nanoparticle shape affects transport across various barriers inside the cell remains unclear. Here we used pair correlation microscopy to show that polymeric nanoparticles with different shapes but identical surface chemistries moved across the various cellular barriers at different rates, ultimately defining the site of drug release. We measured how micelles, vesicles, rods and worms entered the cell and whether they escaped from the endosomal system and had access to the nucleus via the nuclear pore complex. Rods and worms, but not micelles and vesicles, entered the nucleus by passive diffusion. Improving nuclear access, for example with a nuclear localization signal, resulted in more doxorubicin release inside the nucleus and correlated with greater cytotoxicity. Our results therefore demonstrate that drug delivery across the major cellular barrier, the nuclear envelope, is important for doxorubicin efficiency and can be achieved with appropriately shaped nanoparticles.

Pair correlation microscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release

The requirement for deoxygenation in controlled/living radical polymerisation (CLRP) places significant limitations on its widespread implementation by necessitating the use of large reaction volumes, sealed reaction vessels as well as requiring access to specialised equipment such as a glove box and/or inert gas source. As a result, in recent years there has been intense interest in developing strategies for overcoming the effects of oxygen inhibition in CLRP and therefore remove the necessity for deoxygenation. In this review, we highlight several strategies for achieving oxygen tolerant CLRP including: “polymerising through” oxygen, enzyme mediated deoxygenation and the continuous regeneration of a redox-active catalyst. In order to provide further clarity to the field, we also establish some basic parameters for evaluating the degree of “oxygen tolerance” that can be achieved using a given oxygen scrubbing strategy. Finally, we propose some applications that could most benefit from the implementation of oxygen tolerant CLRP and provide a perspective on the future direction of this field.

Jonathan Yeow

Papers

Copper-Mediated Living Radical Polymerization (Atom Transfer Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications

Seeing the Light: Advancing Materials Chemistry through Photopolymerization.

Emerging trends in polymerization-induced self-assembly

Pair correlation microscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release

Up in the air: oxygen tolerance in controlled/living radical polymerisation