Targeted Graphene Oxide Networks: Cytotoxicity and Synergy with Anticancer Agents.

An effective strategy to inhibit endocytosis in cancer cells is presented where modified net-type graphene oxide (GO) sheets, bound with multiple cell surface receptors, are introduced and synthesized as novel anticancer agents. The results suggest that the binding connects GO sheets with neighboring lipid rafts, neutralizes endocytosis, and causes metabolic deprivation. As a result, tumor cell survival and proliferation are reduced.

Precise control of drug loading and release of an NSAID-polymer conjugate for long term osteoarthritis intra-articular drug delivery.

A facile synthesis method of polymer diclofenac conjugates (PDCs) based on biocompatible polyurethane chemistry that provides a high drug loading and offers a high degree of control over diclofenac (DCF) release kinetics is described. DCF incorporating monomer was reacted with ethyl-l-lysine diisocyanate (ELDI) and different amounts of polyethylene glycol (PEG) in a one-step synthesis to yield polymers with pendent diclofenac distributed along the backbone. By adjusting the co-monomers feed ratio, the drug loading could be tailored accordingly to give DCF loading of up to 38 w/w%.

Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers.

With the recent emergence of reports on resistant Gram-negative 'superbugs', infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed 'structurally nanoengineered antimicrobial peptide polymers' (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy.

Controlled Formation of Star Polymer Nanoparticles via Visible Light Photopolymerization.

A recently developed visible light mediated photocontrolled radical polymerization technique using trithiocarbonates (i.e., conventional RAFT agents) as the sole control agent in the absence of additional photoinitiators or catalysts is utilized for the synthesis of core cross-linked star (CCS) polymer nanoparticles.

Polypeptide films via N-carboxyanhydride ring-opening polymerization (NCA-ROP): past, present and future.

The formation of surface-grafted polypeptide films and interfaces via N-carboxyanhydride ring-opening polymerization (NCA-ROP) holds great potential for the facile preparation of next-generation multifunctional and responsive materials with excellent biocompatibility, biodegradability, tunable conformations and chemical functionalities. Therefore, the aim of this feature article is to provide a topical review of developments in the area of polypeptide films derived through NCA-ROP. It is evident that studies reported thus far have only started to unveil the full potential of peptide-based interfaces and materials, and with continued advancements it is anticipated that the strategic combination of NCA-ROP with modern synthetic chemistries will continue to yield versatile platforms for broader applications in the fields of polymer therapeutics, tissue engineering, (bio)nanocoatings, (bio)chemosensors, catalysis and separation technologies.

Assembly of free-standing polypeptide films via the synergistic combination of hyperbranched macroinitiators, the grafting-from approach, and cross-chain termination.

Cross-linked polypeptide-based films are fabricated via a novel and robust method employing surface-initiated ring opening polymerization of α-amino acid N-carboxyanhydrides (NCA-ROP). The judicious combination of amine-based hyperbranched macroinitiators and benzyl ester-protected NCA derivatives promotes network formation by cross-chain terminations, which allows the formation of stable cross-linked peptide-based capsules in a one-pot system.

Stabilization of peptide-based vesicles via in situ oxygen-mediated cross-linking.

Reversible vesicles from poly(L-glutamic acid)(65) -block-poly[(L-lysine)-ran-(L-3,4-dihydroxyphenylalanine)](75) [PLGA(65)-b-P(LL-r-DOPA)(75)] block copolypeptide adopt different configurations depending on the surrounding pH. At pH = 3, AFM and TEM images show ellipsoidal morphologies, whereas at pH = 12 both TEM and AFM reveal the formation of hollow vesicles. At pH = 12, the P(LL-r-DOPA) block forms the internal layer of the vesicle shell and the subsequent oxygen-mediated oxidation of the phenolic groups of the DOPA lead to the formation of quinonic intermediates, which undergo intermolecular dimerization to stabilize the vesicles via in situ cross-linking.

Folic acid conjugated amino acid-based star polymers for active targeting of cancer cells.

Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L-cystine)(core)) with peripheral allyl functionalities were synthesized by sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs) via the arm-first approach, using N-(trimethylsilyl)allylamine as the initiator. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic acid conjugate via thiol-ene click chemistry afforded poly(PEG-b-L-lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with folic acid targeting moieties. Similarly, a control was prepared without folic acid, using just PEG.

Star polymers composed entirely of amino acid building blocks: a route towards stereospecific, biodegradable and hierarchically functionalized stars.

Highly functionalized water soluble core cross-linked star (CCS) polymers having degradable cores and hierarchical functionalities spanning from the peripheral groups along the arms to the core have been synthesized entirely from amino acid building blocks. The core-isolated moieties were shown to undergo further reactions, such as click chemistry, as well as being capable of encapsulating water-insoluble drugs.

Chemical modification of gelatin by a natural phenolic cross-linker, tannic acid.

Chemical modification of gelatin by a natural phenolic compound tannic acid (TA) at pH 8 was studied, and the properties of the modified gelatin materials were examined. The cross-linking effect was predominant when the TA content was lower, resulting in the formation of a partially insoluble cross-link network. The cross-linking structure was stable even under boiling, and the protein matrix became rigid, whereas the mechanical properties were enhanced.

Chemical cross-linking gelatin with natural phenolic compounds as studied by high-resolution NMR spectroscopy.

Cross-linking gelatin with natural phenolic compound caffeic acid (CA) or tannic acid (TA) above pH 9 resulted in formation of insoluble hydrogels. The cross-linking reactivity was controlled by variation of pH, the concentration of the gelatin solution, or the amount of CA or TA used in the reaction. The cross-linking chemistry was studied by high-resolution NMR technique in both solution and solid state via investigation on small molecular model systems or using (13)C enriched caffeic acid (LCA) in the reaction with gelatin.