A soft robotic fish can quickly swim and turn with a fully integrated onboard system for power and remote control.

No abstract

Exosomes (Exo) hold great promise as endogenous nanocarriers that can deliver biological information between cells. However, Exo are limited in terms of their abilities to target specific recipient cell types. We developed a strategy to isolate Exo exhibiting increased binding to integrin α v β 3 . Binding occurred through a modified version of a disintegrin and metalloproteinase 15 (A15) expressed on exosomal membranes (A15-Exo), which facilitated co-delivery of therapeutic quantities of doxorubicin (Dox) and cholesterol-modified miRNA 159 (Cho-miR159) to triple-negative breast cancer (TNBC) cells, both in vitro and in vivo. The targeted A15-Exo were derived from continuous protein kinase C activation in monocyte-derived macrophages. These cell-derived Exo displayed targeting properties and had a 2.97-fold higher production yield. In vitro, A15-Exo co-loaded with Dox and Cho-miR159 induced synergistic therapeutic effects in MDA-MB-231 cells. In vivo, miR159 and Dox delivery in a vesicular system effectively silenced the TCF-7 gene and exhibited improved anticancer effects, without adverse effects. Therefore, our data demonstrate the synergistic efficacy of co-delivering miR159 and Dox by targeted Exo for TNBC therapy.

We report a new class of deubiquitinating enzyme (DUB) probes that resemble the native diubiquitin with a same linkage size and contain a Michael addition acceptor for trapping the DUB active-site cysteine. Both K63- and K48-linked diubiquitin probes were generated using a facile chemical ligation method. The diUb probes were demonstrated to label DUBs from different families and revealed intrinsic linkage specificities of DUBs.

No abstract

Cancer immunotherapy can enhance the antitumor effect of drugs through a combinatorial approach in a synergistic manner. However, the effective targeted delivery of various drugs remains a challenge. We generated a peptide assembling tumor-targeted nanodelivery system based on a breast cancer homing and penetrating peptide for the codelivery of a programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) (siPD-L1) and an indoleamine 2,3-dioxygenase inhibitor as a dual blockade of an immune checkpoint. The vector is capable of specifically accumulating in the breast cancer tumor site in a way that allows the siRNA to escape from endosomal vesicles after being endocytosed by tumor cells. The drug within these cells then acts to block tryptophan metabolism. The results showed that locally released siPD-L1 and 1-methyl-dl-tryptophan favor the survival and activation of cytotoxic T lymphocytes, resulting in apoptosis of breast cancer cells. Therefore, this study provides a potential approach for treating breast cancer by blocking immunological checkpoints through the assembly of micelles with functional peptides.

Robots for underwater exploration are typically comprised of rigid materials and driven by propellers or jet thrusters, which consume a significant amount of power. Large power consumption necessitates a sizeable battery, which limits the ability to design a small robot. Propellers and jet thrusters generate considerable noise and vibration, which is counterproductive when studying acoustic signals or studying timid species. Bioinspired soft robots provide an approach for underwater exploration in which the robots are comprised of compliant materials that can better adapt to uncertain environments and take advantage of design elements that have been optimized in nature. In previous work, we demonstrated that frameless DEAs could use fluid electrodes to apply a voltage to the film and that effective locomotion in an eel-inspired robot could be achieved without the need for a rigid frame. However, the robot required an off-board power supply and a non-trivial control signal to achieve propulsion. To develop an untethered soft swimming robot powered by DEAs, we drew inspiration from the jellyfish and attached a ring of frameless DEAs to an inextensible layer to generate a unimorph structure that curves toward the passive side to generate power stroke, and efficiently recovers the original configuration as the robot coasts. This swimming strategy simplified the control system and allowed us to develop a soft robot capable of untethered swimming at an average speed of 3.2 mm/s and a cost of transport of 35. This work demonstrates the feasibility of using DEAs with fluid electrodes for low power, silent operation in underwater environments.

Two new bis(benzimidazole)aryl derivatives have been prepared and one of them has been shown to induce and stabilize formation of a G-quadruplex.