Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

Graphene-Like Two-Dimensional Materials

Controlled/living radical polymerization: Features, developments, and perspectives

Current status and future perspectives in atom transfer radical polymerization (ATRP) are presented. Special emphasis is placed on mechanistic understanding of ATRP, recent synthetic and process development, and new controlled polymer architectures enabled by ATRP. New hybrid materials based on organic/inorganic systems and natural/synthetic polymers are presented. Some current and forthcoming applications are described.

Atom Transfer Radical Polymerization (ATRP): Current Status and Future Perspectives

Polymeric Nanoparticles for Drug Delivery

Despite recent intensive research, especially focused on the design of different nitroxide structures, the control of methacrylic esters is still an important challenge for NMP. This chapter aims at covering not only the main reasons for the difficulty achieving NMP of methacrylates but also the most successful strategies that have been developed to control the polymerization of such monomers by NMP.

Chapter 7:NMP of Methacrylic Esters: How to Circumvent a Long-time Obstacle

The synthesis of degradable vinyl polymer nanoparticles/latexes in aqueous dispersed media is receiving much attention, particularly for biomedical applications and plastic pollution control, as it can circumvent the severe limitations associated with emulsification of preformed degradable polymers. Polymerisation-induced self-assembly (PISA), which enables the in-situ formation of aqueous suspensions of diblock copolymer nano-objects of high solids content, has become a very popular polymerization process due to its many advantages in terms of simplicity, robustness, scalability and versatility. However, the preparation of degradable vinyl polymer nanoparticles by direct aqueous PISA has never been reported. This severely limits the use of PISA in biomedical and environmental applications. Herein, we report the first aqueous emulsion PISA able to generate degradable vinyl polymer nanoparticles. It relies on radical ring-opening polymerization-induced self-assembly (rROPISA) of traditional vinyl monomers ( n -butyl acrylate or styrene) with dibenzo[c,e]oxepane-5-thione (DOT), a thionolactone that features high stability in protic solvents and favourable reactivity with many vinyl monomers, and is a precursor of labile thioester groups in the main chain. Stable aqueous suspensions of thioester-containing diblock copolymer nanoparticles were obtained with both vinyl monomers. Extensive degradation of the copolymers and the nanoparticles was successfully demonstrated under aminolytic or basic conditions. Given the success of the PISA process within the polymer community, this work has the potential to greatly expand its use in many areas, from nanomedicine (providing an extension to biocompatible vinyl polymers) to sustained materials in the context of the polymer circular economy.

Degradable Vinyl Polymer Nanoparticles/Latexes by Aqueous Nitroxide-Mediated Polymerization-Induced Self-Assembly

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Increasing the Hydrophilicity of Cyclic Ketene Acetals Improves the Hydrolytic Degradation of Vinyl Copolymers and the Interaction of Glycopolymer Nanoparticles with Lectins.

La presente invention concerne un procede de polymerisation radicalaire en emulsion, mini-emulsion ou micro-emulsion mettant en œuvre au moins une alcoxyamine hydrosoluble. Ce procede permet de preparer des (co)polymeres multiblocs, notamment diblocs et triblocs.

Julien Nicolas

Papers

Polymeric Nanoparticles for Drug Delivery

Chapter 7:NMP of Methacrylic Esters: How to Circumvent a Long-time Obstacle

Degradable Vinyl Polymer Nanoparticles/Latexes by Aqueous Nitroxide-Mediated Polymerization-Induced Self-Assembly

Increasing the Hydrophilicity of Cyclic Ketene Acetals Improves the Hydrolytic Degradation of Vinyl Copolymers and the Interaction of Glycopolymer Nanoparticles with Lectins.

Procede de polymerisation radicalaire en emulsion mettant en oeuvre des alcoxyamines hydrosolubles