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.

/pdf/principles-of-nanoparticle-design-for-overcoming-biological-4c2c5quqtc.pdf

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.

/pdf/cancer-nanomedicine-progress-challenges-and-opportunities-3dukbks14n.pdf

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

Poly(alkyl cyanoacrylate) nanosystems include various types of nanoparticles suitable to achieve in vivo drug delivery in a well controlled manner. Starting from general features on the synthesis of alkyl cyanoacrylate monomers and of their polymerization, this chapter aims to discuss how these monomers and corresponding polymers can be used to design drug delivery nanosystems with different properties.

Poly(Alkyl Cyanoacrylate) Nanosystems

Polymer–Protein/Peptide Bioconjugates

Drug-polymer conjugates that can self-assemble into nanoparticles are promising drug delivery systems that improve the drug bioavailability and allow their controlled release. However, despite the possibility of reaching high drug loadings, the efficiency of the drug release, mediated by cleavage of the drug-polymer linker, is a key parameter to obtain significant anticancer activity. To overcome the limitations of experimental characterizations and to gain a better understanding of such systems, we conducted a coarse-grained molecular dynamics simulation study on four representative drug-polymer conjugates obtained by the "drug-initiated" method and studied their supramolecular organization upon self-assembly. The prodrugs were composed of either a gemcitabine or a paclitaxel anticancer drug, either a propanoate or a diglycolate linker, and a polyisoprene chain. Our simulations gave crucial information concerning the spatial organization of the different components (e.g., drug, linker, polymer, etc.) into the nanoparticles and revealed that the linkers are not fully accessible to the solvent. Notably, some cleavage sites were either poorly hydrated or partially solvated. These observations might account for the low efficiency of drug release from the nanoparticles, particularly when the linker is too short and/or not hydrophilic/solvated enough. We believe that our theoretical study could be adapted to other types of polymer prodrugs and could guide the design of new polymer prodrug nanoparticles with improved drug release efficiency.

Supramolecular Organization of Polymer Prodrug Nanoparticles Revealed by Coarse-Grained Simulations

Process of polymerization comprises radical polymerization of the monomer in mini-emulsion, micro-emulsion or emulsion in the presence of at least one water-soluble alkoxyamine. A polymerization process comprises radical polymerization of the monomer in mini-emulsion, micro-emulsion or emulsion in the presence of at least one water-soluble alkoxyamine of formula (I). R 11-3C alkyl; and R 2alkaline metal such as Li, Na or K, or ammonium ion such as NH 4 +>, NBu 4 +> or NHBu 3 +>. Independent claims are also included for: (1) preparation of multiblock polymers comprising preparing a first block, introducing a second monomer or a mixture of monomers-different from the first block without stopping the agitation, without recooling or other interruption, and optionally introducing a monomer or a mixture of monomers different from the second block (where the polymer blocks are constituted based on the nature of the monomers); (2) polymer particle comprising a polymer obtained by the process; and (3) a latex comprising a group of particles. [Image].

Polymerization process, useful to prepare multiblock (co)polymers, comprises radical polymerization of monomer in mini-emulsion, micro-emulsion or emulsion in the presence of water-soluble alkoxyamine

The simple, one step synthesis of aqueous suspensions of amphiphilic nanoparticles is presented. Those particles are prepared in the batch heterophase polymerization of styrene or n-butyl acrylate, using a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator. The nitroxide-mediated controlled growth of the hydrophobic block leads to the formation of poly(sodium acrylate)-b-polystyrene or poly(sodium acrylate)-b-poly(n-butyl acrylate) amphiphilic diblock copolymers, able to self-assemble in water simultaneously to the growth step. When the diblock copolymers become strongly asymmetrical, with a short poly(sodium acrylate) block and a long hydrophobic one, the formed hairy nanoparticles are analogous to amphiphilic diblock copolymer crew-cut micelles.

Aqueous suspension of amphiphilic diblock copolymer nanoparticles prepared in situ from a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator

Julien Nicolas

Papers

Poly(Alkyl Cyanoacrylate) Nanosystems

Polymer–Protein/Peptide Bioconjugates

Supramolecular Organization of Polymer Prodrug Nanoparticles Revealed by Coarse-Grained Simulations

Polymerization process, useful to prepare multiblock (co)polymers, comprises radical polymerization of monomer in mini-emulsion, micro-emulsion or emulsion in the presence of water-soluble alkoxyamine

Aqueous suspension of amphiphilic diblock copolymer nanoparticles prepared in situ from a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator