Photocontrolled Growth of Cross-Linked Nanonetworks.

We report the preparation of photoresponsive nanomaterials and the increase of their nanoscopic size through a "photogrowth" mechanism. The photogrowable nanonetworks (PGNNs) were synthesized by cross-linking two components, a thiolated acrylate copolymer and a symmetrical bismaleimide trithiocarbonate (TTC), utilizing thiol-maleimide click chemistry. With this strategy, nanonetwork growth was achieved through a photoinduced polymerization from the integrated trithiocarbonate by either direct photolysis or photoredox catalysis. Via direct photolysis, we generated a series of expanded particles by polymerizing methyl acrylate (MA) under irradiation with violet light (400 nm) over a period of 1, 3, and 6 h, starting from a 58 nm parent particle, resulting in particles of increased sizes of 77, 156, and 358 nm, respectively. Nanoparticle expansion reactions catalyzed by 10-phenylphenothiazine (PTH) were experienced to progress faster in 20 and 30 min to reach particle sizes of 195 and 300 nm. The addition of the photoredox catalyst to the expansion polymerizations with MA resulted in an increased control over the dispersity of the particles as well as of the promoted disassembly products. In this work, we demonstrated that nanoparticle structures designed as cross-linked networks with integrated trithiocarbonates can be expanded by photocontrolled radical polymerizations (photo-CRPs) in the presence or absence of a photoredox catalyst. These proof-of-concept experiments showcase the dynamic growth and integration of functional units into existing scaffolds and open up the possibility to prepare highly tailorable nanomaterials.

Matrices for combined delivery of proteins and synthetic molecules.

With the increasing advancement of synergistic, multimodal approaches to influence the treatment of infectious and non-infectious diseases, we witness the development of enabling techniques merging necessary complexity with leaner designs and effectiveness. Systems- and polypharmacology ask for multi-potent drug combinations with many targets to engage with the biological system. These demand drug delivery designs for one single drug, dual drug release systems and multiple release matrices in which the macromolecular structure allows for higher solubilization, protection and sequential or combined release profiles. As a result, nano- and micromaterials have been evolved from mono- to dual drug carriers but are also an essential part to establish multimodality in polymeric matrices. Surface dynamics of particles creating interfaces between polymer chains and hydrogels inspired the development not only of biomedical adhesives but also of injectable hydrogels in which the nanoscale material is both, adhesive and delivery tool. These complex delivery systems are segmented into two delivery subunits, a polymer matrix and nanocarrier, to allow for an even higher tolerance of the incorporated drugs without adding further synthetic demands to the nanocarrier alone. The opportunities in these quite novel approaches for the delivery of small and biological therapeutics are remarkable and selected examples for applications in cancer and bone treatments are discussed.

Precise Microscale Polymeric Networks through Piezoelectronic Inkjet Printing.

Microsized particles are versatile drug delivery systems with applications as inhalants, implants, and vaccines. An ideal fabrication technique is envisioned to provide particles with controlled size dimensions and is facile, without excessive loss of drug during incorporation, modulated morphologies and release kinetics. In this work, we report on the utilization of a set of polymeric building blocks such as allyl- functionalized polycarbonates, semibranched poly(glycidol allylglycidyl ether)s, and dithiol-PEG cross-linkers to form microsized networks in controlled size dimensions of 18-12 µm, 12-8 µm, and 1-2 µm with modulated morphologies and hydrophilicity based on the ratio of the polycarbonate or polyglycidol building blocks. Piezoelectric ink jet printing allows for the direct printing of these polymeric structures onto substrates, after which the printed droplet is cross-linked via UV light using thiol-ene click reactions. By varying the ratio of the allyl-functionalized building block droplets from being purely prepared either from polycarbonate (PC), polyglycidol (PG) backbones or in a ratio of 70/30 of functionalized polycarbonates and polyglycidols, the droplets can be either printed in DMSO or water. Preliminary studies to control the particle sizes not only through the droplet volume but also by reducing the polymer concentration by 20%, resulted in another set of 70/30 polycarbonate/polyglycidol micron sized networks with an observed corresponding size reduction of 20%. With this, we have developed a facile technique to prepare microsized hydrogel particles with homogeneous and attractive size dimensions that can be directly prepared without using lithography methodologies. The strength of the approach is the set of unique polymeric building blocks that in combination with the new technique allows for a modulation of hydrophilicity and morphologies to form promising drug delivery candidates to carry and release synthetic as well as biological cargo.