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Glucose-responsive glycol chitosan/sodium alginate-poly(l-glutmate-co-N-3-l-glutamylphenylboronic acid) double-layered nanogel is a promising platform for controlled insulin release systems, achieving glucose-triggered insulin release at diabetic glucose levels in vivo.

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Perturbation of potassium homeostasis can affect various cell functions and lead to the onset of programmed cell death. Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death are unclear and the bioapplicability is limited. In this study, helical polypeptide‐based potassium ionophores are developed to induce endoplasmic reticulum (ER) stress‐mediated apoptosis. The polypeptide‐based potassium ionophores disturb ion homeostasis and then induce prolonged ER stress in the cells. The ER stress results in oxidative environments that accelerate the activation of mitochondria‐dependent apoptosis. Moreover, ER stress‐mediated apoptosis is triggered in a tumor‐bearing mouse model that suppresses tumor proliferation. This study provides the first evidence showing that helical polypeptide‐based potassium ionophores trigger ER stress‐mediated apoptosis by perturbation of potassium homeostasis.

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Curcumin (CRC) has been widely used as a therapeutic agent for various drug delivery applications. In this work, we focused on the applicability of CRC as a nanodrug delivery agent for doxorubicin hydrochloride (DOX) (commercially known as Adriamycin) coated with poly(ethylene glycol) (PEG) as an effective therapeutic strategy against multidrug-resistant cancer cells. The developed PEG-coated CRC/DOX nanoparticles (NPs) (PEG-CRC/DOX NPs) were well localized within the resistant cancer cells inducing apoptosis confirmed by flow cytometry and DNA fragmentation assays. The PEG-CRC/DOX NPs suppressed the major efflux proteins in DOX-resistant cancer cells. The in vivo biodistribution studies on HCT-8/DOX-resistant tumor xenograft showed improved bioavailability of the PEG-CRC/DOX NPs, and thereby suppressed tumor growth significantly compared to the other samples. This study clearly shows that curcumin nanoparticles could deliver DOX efficiently into the multidrug-resistant cancer cells to have potential therapeutic benefits.

BackgroundCell penetrating peptides (CPPs) as one class of non-viral vectors, have been widely explored as a delivery tool due to their cell-penetrating capability with low cytotoxicity. However, CPPs have reported to have low gene transfection efficiency mainly due to the fact that DNA is larger than other biomolecules. On the other hand, the conventional linear CPPs are unstable for constructing the DNA complexes with it. Thus, here we designed a branched CPP using disulfide bridges based on the linear TAT peptide, to enhance the gene delivery efficiency in a better way.ResultsThe branched TAT (BTAT) was synthesized by the DMSO oxidation method and showed high-molecular-weight about 294 kDa. The resulting BTAT was complexed with plasmid green fluorescence protein (pGFP) gene at various N/P ratios. The gene transfection efficiency was assessed on HeLa cells after treating with BTAT/pGFP complexes, showed high gene transfection efficiency as conformed by flowcytometry followed by confocal laser scanning microscopy (CLSM) visualization.ConclusionThe novel BTAT/pGFP complex exhibited significantly higher stability and redox cleavability by reducing agent. In addition, BTAT showed higher transfection efficiency approximately 40-fold than those of the TAT and mTAT complexes. Our primary experiments demonstrated the potential of BTAT as a suitable candidate for gene delivery and it could be applied for various types of gene delivery platforms.