Cationic Poly(Amino Acid) Vaccine Adjuvant for Promoting Both Cell-Mediated and Humoral Immunity Against Influenza Virus.

Powerful adjuvants to augment vaccine efficacy with a less immunogenic vaccine system are in great demand. In this study, a novel squalene-based cationic poly(amino acid) adjuvant (CASq) that elicits both cellular (Th1) and humoral (Th2) immune responses is developed. CASq is demonstrated to promote cellular uptake of viral antigen and stimulate macrophages, leading to active production of interleukin-12. Furthermore, co-administration of inactivated pdm H1N1 vaccine with CASq significantly increases the generation of antigen-specific antibodies and T cell immune responses in mice, as well as resulting in complete prevention of disease symptoms and protection against lethal infection.

Host Cell Mimic Polymersomes for Rapid Detection of Highly Pathogenic Influenza Virus via a Viral Fusion and Cell Entry Mechanism.

Highly pathogenic avian influenza virus (HPAIV) infections have occurred continuously and crossed the species barrier to humans, leading to fatalities. A polymerase chain reaction based molecular test is currently the most sensitive diagnostic tool for HPAIV; however, the results must be analyzed in centralized diagnosis systems by a trained individual. This requirement leads to delays in quarantine and isolation. To control the spread of HPAIV, rapid and accurate diagnostics suitable for field testing are needed, and the tests must facilitate a differential diagnosis between HPAIV and low pathogenic avian influenza virus (LPAIV), which undergo cleavage specifically by trypsin- or furin-like proteases, respectively. In this study, a differential avian influenza virus rapid test kit is developed and evaluated in vitro and using clinical specimens from HPAIV H5N1-infected animals. It is demonstrated that this rapid test kit provides highly sensitive and specific detection of HPAIV and LPAIV and is thus a useful field diagnostic tool for H5N1 HPAIV outbreaks and for rapid quarantine control of the disease.

Correction: Stent containing CD44-targeting polymeric prodrug nanoparticles that release paclitaxel and gemcitabine in a time interval-controlled manner for synergistic human biliary cancer therapy.

Correction for 'Stent containing CD44-targeting polymeric prodrug nanoparticles that release paclitaxel and gemcitabine in a time interval-controlled manner for synergistic human biliary cancer therapy' by Dayeon Yun et al., J. Mater. Chem. B, 2017, 5, 6317-6324.

Stent containing CD44-targeting polymeric prodrug nanoparticles that release paclitaxel and gemcitabine in a time interval-controlled manner for synergistic human biliary cancer therapy.

The use of drug-eluting stents (DESs) is a promising strategy for non-vascular diseases, especially human biliary cancer. However, the implementation of DESs suffers from two major obstacles: the side effects of drugs and the difficulty of controlling the drug release. These problems can be overcome if the stent elutes targeting nanoparticles that release drugs at time intervals that are dictated by the mechanisms of those drugs. We designed temporally controlled polymeric multi-prodrug nanoparticles (TCMPNs) that can be eluted from stents comprising polyurethane (PU) nanofiber as a polymeric matrix and paclitaxel (PTX)-loaded, CD44-targeting, hyaluronic acid-conjugated poly(lactic-co-glycolic acid) and gemcitabine (GEM) (P-H-G). TCMPNs enable two different types of drugs to be released temporally; PTX is released first owing to the collapse of the structure in the endosomes, and GEM, which induces synergistic anticancer activities, is hydrolyzed from P-H-G later in response to low pH. Embedded in the PU nanofiber, the TCMPNs demonstrate low initial burst behavior and sustainable release of the prodrug in vitro. Furthermore, TCMPN-eluting stents (TESs) exhibit continuous synergistic efficacy as available targeted cellular uptake prodrug delivery systems in tumor-bearing mice. These results demonstrate that this technology will open up cancer therapy by combining localized delivery and functional multi-drug-loaded nanoparticles.

Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells.

Real-time quantitative and qualitative analyses of metastasis-associated proteases are critical for precise diagnosis and novel therapeutic treatment of advanced cancers. However, conventional methods based on DNA, peptides, and proteins require sophisticated chemistry and additional processes to expose detection moieties, and they lack elements of temporal control, which limit their applicability. We designed unique protease-activatable polymersomes (PeptiSomes) for high sensitivity, in situ quantitative analysis of activating membrane-type 1 matrix metalloproteinases (MT1-MMP, MMP14). To do this, we first synthesized an amphiphilic block polymer-peptide and a copolypeptide based on mPEG-b-pLeu and MT1-peptide-b-pLeu, respectively. Amphiphilic self-assembled PeptiSomes in water were capable of disassembling and releasing the encapsulated self-quenched fluorescence dye (calcein) via enzymatic activation by MT1-MMP. Our PeptiSome system may potentially prevent the initiation and progression of cancer metastasis. Furthermore, the PeptiSome approach described here is likely to facilitate the development of rapid protease assay techniques and further extend the role of proteases as metastasis indicators and therapeutic targets.