This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made with regard to the development of electrospinning methods and engineering of electrospun nanofibers to suit or enable various applications. We aim to provide a comprehensive overview of electrospinning, including the principle, methods, materials, and applications. We begin with a brief introduction to the early history of electrospinning, followed by discussion of its principle and typical apparatus. We then discuss its renaissance over the past two decades as a powerful technology for the production of nanofibers with diversified compositions, structures, and properties. Afterward, we discuss the applications of electrospun nanofibers, including their use as "smart" mats, filtration membranes, catalytic supports, energy harvesting/conversion/storage components, and photonic and electronic devices, as well as biomedical scaffolds. We highlight the most relevant and recent advances related to the applications of electrospun nanofibers by focusing on the most representative examples. We also offer perspectives on the challenges, opportunities, and new directions for future development. At the end, we discuss approaches to the scale-up production of electrospun nanofibers and briefly discuss various types of commercial products based on electrospun nanofibers that have found widespread use in our everyday life.

Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications

The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo

The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.

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Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

Advances in nanoparticle synthesis and engineering have produced nanoscale agents affording both therapeutic and diagnostic functions that are often referred to by the portmanteau 'nanotheranostics'. The field is associated with many applications in the clinic, especially in cancer management. These include patient stratification, drug-release monitoring, imaging-guided focal therapy and post-treatment response monitoring. Recent advances in nanotheranostics have expanded this notion and enabled the characterization of individual tumours, the prediction of nanoparticle-tumour interactions, and the creation of tailor-designed nanomedicines for individualized treatment. Some of these applications require breaking the dogma that a nanotheranostic must combine both therapeutic and diagnostic agents within a single, physical entity; instead, it can be a general approach in which diagnosis and therapy are interwoven to solve clinical issues and improve treatment outcomes. In this Review, we describe the evolution and state of the art of cancer nanotheranostics, with an emphasis on clinical impact and translation.

Rethinking cancer nanotheranostics.

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.

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

Intolerance to oxygen is a key limitation in many reactions and particularly in controlled radical polymerizations. Here we introduce the use of enzymes such as glucose oxidase (GOx) to deoxygenate reversible addition–fragmentation chain transfer polymerizations (Enz-RAFT), facilitating the preparation of highly controlled polymers in vessels open to ambient oxygen. Because the removal of oxygen is so efficient, very low concentrations of GOx and initiator can be used, enabling excellent control which is demonstrated by pseudoliving polymerization kinetics and the preparation of multiblock copolymers with narrow molecular weight distributions (Mw/Mn < 1.15). GOx retains sufficient activity to facilitate polymerization not only in aqueous solutions but also in a range of water/organic solvent mixtures, and we demonstrate the use of this technique to perform open vessel Enz-RAFT polymerizations in various methanol and dioxane/water mixtures.

Highly Controlled Open Vessel RAFT Polymerizations by Enzyme Degassing

The complexity of polymer-protein interactions makes rational design of the best polymer architecture for any given biointerface extremely challenging, and the high throughput synthesis and screening of polymers has emerged as an attractive alternative. A porphyrin-catalysed photoinduced electron/energy transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerisation was adapted to enable high throughput synthesis of complex polymer architectures in dimethyl sulfoxide (DMSO) on low-volume well plates in the presence of air. The polymerisation system shows remarkable oxygen tolerance, and excellent control of functional 3- and 4-arm star polymers. We then apply this method to investigate the effect of polymer structure on protein binding, in this case to the lectin concanavalin A (ConA). Such an approach could be applied to screen the structure-activity relationships for any number of polymer-protein interactions.

An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure-Activity Relationships.

The synthesis of well-defined polymers in a low-volume, combinatorial fashion has long been a goal in polymer chemistry. Here, we report the preparation of a wide range of highly controlled homo and block co-polymers by Enz-RAFT (enzyme-assisted reversible addition–fragmentation chain transfer) polymerization in microtiter plates in the open atmosphere. The addition of 1 μm glucose oxidase (GOx) to water/solvent mixtures enables polymerization reactions to proceed in extremely low volumes (40 μL) and low radical concentrations. This procedure provides excellent control and high conversions across a range of monomer families and molecular weights, thus avoiding the need to purify for screening applications. This simple technique enables combinatorial polymer synthesis in microtiter plates on the benchtop without the need of highly specialized synthesizers and at much lower volumes than is currently possible by any other technique.

Combinatorial Low-Volume Synthesis of Well-Defined Polymers by Enzyme Degassing

https://www.materialstoday.com/download/50976/

Adam J. Gormley

Papers

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

Highly Controlled Open Vessel RAFT Polymerizations by Enzyme Degassing

An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure-Activity Relationships.

Combinatorial Low-Volume Synthesis of Well-Defined Polymers by Enzyme Degassing

Guided delivery of polymer therapeutics using plasmonic photothermal therapy