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Toll-like receptor (TLR) agonists are being developed as anti-cancer therapeutics due to their potent immunostimulatory properties. However, clinical trials testing TLR agonists as monotherapy have often failed to demonstrate significant improvement over standard of care. We hypothesized that the anti-cancer efficacy of TLR agonist immunotherapy could be improved by combinatorial approaches. To prevent increased toxicity, often seen with systemic combination therapies, we developed a hydrogel to deliver TLR agonist combinations at low doses, locally, during cancer debulking surgery. Using tumor models of WEHI 164 and bilateral M3–9-M sarcoma and CT26 colon carcinoma, we assessed the efficacy of pairwise combinations of poly(I:C), R848, and CpG in controlling local and distant tumor growth. We show that combination of the TLR3 agonist poly(I:C) and TLR7/8 agonist R848 drives anti-tumor immunity against local and distant tumors. In addition, combination of local poly(I:C) and R848 sensitized tumors to systemic immune checkpoint blockade, improving tumor control. Mechanistically, we demonstrate that local therapy with poly(I:C) and R848 recruits inflammatory monocytes to the tumor draining lymph nodes early in the anti-tumor response. Finally, we provide proof of concept for intraoperative delivery of poly(I:C) and R848 together via a surgically applicable biodegradable hydrogel. [ABSTRACT FROM AUTHOR]

Achieving high transfection efficiencies and tumour cell specificity are key milestones in the development of non-viral gene delivery agents. Here, we demonstrate the effectiveness of a dendronised polymer system functionalised with a targeting peptide to achieve highly selective transient transfection of liver cancer cells over normal non-transformed hepatocytes. The highly specific delivery agent has potential applications in gene therapy and may be worthy of further investigation for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

We present a series of synthetic polymer hydrogels which break the traditional correlation between pore size and mechanical properties. The hydrogels are prepared from a dendronised polymer architecture based on a methacrylate copolymer to which poly(amido amine) dendrons are attached. Our approach will be useful in tailoring hydrogels for tissue engineering, controlled drug release, and flexible electronics. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX) is a widely used chemotherapy drug that is associated with numerous side effects and limited bioavailability. Macromolecular conjugates of DTX may improve drug targeting, solubility, reduce off-target toxicity, and overcome mechanisms of multidrug resistance. However, most polymer conjugates of DTX investigated to date make use of biopolymers, which are of fixed structure and are not well suited to optimisation and subsequent reaction to introduce further functionality. Here, we show the preparation of synthetic copolymer conjugates of DTX with drug loading of up to 20% w/w that also has potential for tuning backbone hydrophilicity and the number of reactive sites for conjugation. The intermediates produced are comprehensively characterised, as are the macromolecular conjugates, which are tested in the MCF-7 human breast adenocarcinoma cell line to assess toxicity and anticancer efficacy. The conjugates produced have IC50 values within one order of magnitude of DTX, as expected for slow release of DTX by ester hydrolysis. The results suggest that the system is promising for delivery of DTX and future work may examine conjugates of a wider molecular weight range, optimisation of DTX and PEG conjugation efficiency, and in vivo biodistribution. [ABSTRACT FROM AUTHOR]

The utility of dendrimers as effective carriers for targeted drug delivery and imaging has been facilitated by a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape characteristics, and multivalency. Dendrimer–quantum dot (QD) nanocomposites have traditionally been synthesised by electrostatic self-assembly of preformed dendrimers and QDs, but higher generations are associated with limited flexibility and increased cytotoxicity. In this paper, we report the fabrication of CdTe QD nanoparticles using a dendronised linear copolymer bearing thiolated fourth-generation poly(amido amine) (PAMAM) dendrons as the capping and stabilising agent. We demonstrate this approach enables synthesis of nanocomposites with aqueous and photophysical stability. This paper describes the synthesis of green and yellow CdTe QD–dendronised polymer nanocomposites in situ using a partially thiolated dendronised polymer as capping agent and stabiliser. [ABSTRACT FROM AUTHOR]

Polymers are an attractive anchoring platform for the synthesis of radioimmunoconjugates. They enable independent control over the amount of radioisotope loading and antibody attachment, which is pivotal in developing tailorable formulations for personalised medicine. Herein, we report the synthesis of p(HEMA-ran-GMA) for the conjugation of lutetium ions and rituximab as a functional platform for radioimmunotherapy. We demonstrate the suitability of this platform using non-Hodgkin's lymphoma cells. [ABSTRACT FROM AUTHOR]

Herein we report a new class of G-quadruplex stabilising ligands, multicarbazoles, which display high G-quadruplex DNA selectivity in the presence of 250 times excess duplex DNA. We report the synthesis of these compounds in moderate to high yields. Ligands in the series with optimal G-quadruplex selectivity contain an N-propylamino chain length where the amino functionalities are either pyrrolidine or piperidine. [ABSTRACT FROM AUTHOR]

The composition of the protein corona formed on poly(ethylene glycol)-functionalized (PEGylated) poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs) was qualitatively and quantitatively compared to the protein corona on non-PEGylated PGMA NPs. Despite the reputation of PEGylated NPs for stealth functionality, we demonstrate the preferential enrichment of specific serum proteins of varied biological function in the protein corona on PEGylated NPs when compared to non-PEGylated NPs. Additionally, we suggest that the base material of polymeric NPs plays a role in the preferential enrichment of select serum proteins to the hard corona. [ABSTRACT FROM AUTHOR]

Chalcones, prepared in high yield in polyethylene glycol, Mw= 300 (PEG300), were screened for inhibition of the thrombin-mediated release of pro-inflammatory interleukin-6 (IL-6) and interleukin-8 (IL-8) from the A549 lung epithelial cell line. Several show significant down-regulation of these pro-inflammatory mediators in a dose-dependant manner with one exhibiting pro-inflammatory properties. Computational studies on selected chalcones revealed a detailed understanding of the structure, electron density and biological activity relationship. [ABSTRACT FROM AUTHOR]

The use of marble in construction is limited by its susceptibility to water spill and weathering. Here, a series of poly (2,2,2-trifluoroethyl methacrylate) (PTFEMA) and poly (methacrylic acid) (PMAA) blend films have been coated on a marble surface to test their water spill and weathering protection capability. The morphologies of the coated polymer films on marble (i.e. surface defects and roughness) were investigated using atomic force microscopy (AFM). The hydrophobicity, adhesion strength and wear resistance of the coated films on marble were evaluated using water contact angle measurement, peel test and nanoindentation, respectively. An optimal combination of characteristics was seen when blending small amounts of PMAA (5% < x < 20 %) with PTFEMA. For these blends, the adhesion to marble and wear resistance of the coated films increased strongly over a pure PTFEMA coating, while maintaining a beneficial high water contact angle. [ABSTRACT FROM AUTHOR]