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Protein therapeutics have gained momentum in recent years and become a pillar in treating many diseases and the only choice in several ailments. Protein therapeutics are highly specific, tunable, and less toxic than conventional small drug molecules. However, reaping the full benefits of therapeutic proteins in the clinics is often hindered by issues of immunogenicity and short half‐life due essentially to fast renal clearance and enzymatic degradation. Advances in polymer chemistry and protein engineering allowed overcoming some of these limitations. Strategies to prolong the half‐life of proteins rely on increasing their size and stability and/or fusing them to endogenous proteins (albumin, Fc fragment of antibody) to hijack physiological pathways involved in protein recycling. On the downside, these modifications might alter therapeutic proteins structure and function. Therefore, a compromise between half‐life and activity is sought. This review covers half‐life extension strategies using natural and synthetic polymers as well as fusion to other proteins and sheds light on genetic engineering strategies and chemical and enzymatic reactions to achieve this goal. Promising strategies and successful applications in the clinics are highlighted. [ABSTRACT FROM AUTHOR]

The aim of the present study was to synthesize a novel biopolymeric micelle based on punicic acid (PA) and polyacrylamide (PAM) for carrying chemotherapeutic drugs used in prostate cancer treatment. A polymer composite micelle was prepared by chemical conjugation between PAM and PA. The micelles were prepared by self‐assembly via film casting followed by ultrasonication method. The successful production of PAMPA copolymeric micelles was confirmed using FTIR, 1H‐NMR, and TEM. Then, flutamide was loaded in the designed nanomicelles and they were characterized. The cell cytotoxicity of the micelles was studied on PC3 cells of prostate cancer. The prepared nanomicelles showed the particle size of 88 nm, PDI of 0.246, zeta potential of −9 mV, drug loading efficiency of 94.5%, drug release of 85.6% until 10 hours in pH 7.4 and CMC of 74.13 μg/ml. The cell viability in blank nanocarriers was about 70% in PC3 cells at concentration of 25 μM. More significant cytotoxic effects were seen for flutamide loaded micelles at this concentration compared to the free drug. The results suggest that the PAMPA co‐polymeric nanomicelles can be utilized as an effective carrier to enhance the cytotoxic effects of flutamide in prostate cancer. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) from peripheral blood account genetic information for cancer diagnosis and overall disease monitoring. Analysis of 'liquid biopsy' holds immense promise as it may lead to new approaches for cancer treatment. The study reports effective and continuous flow microchannel system for isolating CTCs using transferrin conjugated 3D matrix synthesized by crosslinking polyethylene glycol-Fe3O4 nanostructures for rapid and efficient capturing of CTCs. The platform provides option of using multiple microchannel units in series that can influence higher cell-capture efficiency due to increasing cell-substrate contact frequency. CTCs are captured with high efficiency even at low concentration of target cells (~90% at 25 cells per mL blood). Furthermore, the study demonstrates that the cell-capture performance is influenced by topographic interactions between nanostructure based matrix and cancer cells of interest. In addition, this study demonstrates the 'proof of concept' using 3D microchannel system having capacity of simultaneously capturing and permanently eliminating CTCs from peripheral blood samples. Further, the study evaluates clinical samples of colon and breast cancer patients for rapid isolation of CTCs. Conclusively, the present platform demonstrates inordinate capacity for cancer cell sorting, biological studies of CTCs, and cancer metastasis, potentially benefiting the real time liquid biopsy and early prognosis of cancer. [ABSTRACT FROM AUTHOR]

The study of protein self-assembly has attracted great interest over the decades, due to the important role that proteins play in life. In contrast to the major achievements that have been made in the fields of DNA origami, RNA, and synthetic peptides, methods for the design of self-assembling proteins have progressed more slowly. This Concept article provides a brief overview of studies on native protein and artificial scaffold assemblies and highlights advances in designing self-assembling proteins. The discussions are focused on design strategies for self-assembling proteins, including protein fusion, chemical conjugation, supramolecular, and computational-aided de novo design. [ABSTRACT FROM AUTHOR]

The ability to target the adeno-associated virus (AAV) to specific types of cells, by altering the cell-surface receptor it binds, is desirable to generate safe and efficient therapeutic vectors. Chemical attachment of receptor-targeting agents onto the AAV capsid holds potential to alter its tropism, but is limited by the lack of site specificity of available conjugation strategies. The development of an AAV production platform is reported that enables incorporation of unnatural amino acids (UAAs) into specific sites on the virus capsid. Incorporation of an azido-UAA enabled site-specific attachment of a cyclic-RGD peptide onto the capsid, retargeting the virus to the αvβ3 integrin receptors, which are overexpressed in tumor vasculature. Retargeting ability was site-dependent, underscoring the importance of achieving site-selective capsid modification. This work provides a general chemical approach to introduce various receptor binding agents onto the AAV capsid with site selectivity to generate optimized vectors with engineered infectivity. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels are characterized by the drastic and reversible change of their physical properties with temperature. Herein is presented the development of a thermosensitive poly(N‐vinylcaprolactam)‐grafted‐aminated alginate (PNVCL‐g‐Alg‐NH2) having a temperature‐dependent phase transition close to physiological temperature. The hybrid copolymer is formed through the combinational use of chemical and physical methods, that is, carbodiimide chemistry, and ionotrophic gelation by calcium cations. PNVCL‐g‐Alg‐NH2 exhibits a phase transition at ≈35 °C, and temperature‐dependent water uptake. Copolymerization with PNVCL leads to a decrease in the water uptake of aminated alginate, while improving its thermal stability. Model protein (bovine serum albumin) release from PNVCL‐g‐Alg‐NH2 scaffolds indicates a higher rate of release below the lower critical solution temperature (LCST) than that of the above, owing to the fact that PNVCL chains collapse at above the LCST and forms a more compact network. In vitro cytotoxicity and hemocompatibility analyses confirm that PNVCL‐g‐Alg‐NH2 scaffolds are basically non‐cytotoxic and non‐hemolytic. [ABSTRACT FROM AUTHOR]

Shashwat S. Banerjee, Jayant J. Khandare, and co‐workers design a continuous flow microchannel system using transferrin‐mediated three dimensional matrix platform synthesized by crosslinking polyethylene glycol‐Fe3O4 nanostructures, in article number 1600934. The 3D microchannel system offers the benefit of simultaneously capturing and permanently eliminating circulating tumor cells ex vivo of cancer patients. [ABSTRACT FROM AUTHOR]