Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acid-overexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module. Therefore, a 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-conjugated di–PEG–PBA (DSPEPEG-di(PEG–PBA) biomaterial was synthesized. The DSPEPEG-di(PEG–PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6.5 and 7.4. DSPEPEG-di(PEG–PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells. Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.
In this paper, a polydimethylsiloxane (PDMS) fabrication method is introduced. It eliminates the need for conventional fabrication methods, such as photolithography and etching. Only a series of oxygen plasma treatments, silanization, and polyvinyl chloride (PVC) adhesive stencils were used to develop multi-layer designs. The fabrication method was applied to fabricate a PDMS-based drug delivery device with an actively controllable, magnetically actuated valve. Above all, this fabrication method eliminated the use of a power-consuming pump. Fluidic substances were injected into the circular shaped primary chamber through a syringe. A secondary chamber, similar to the primary chamber’s structure but with a smaller radius and thinner membrane, was connected via a microchannel to regulate the amount released. When actuated with a permanent magnet for one second, the volume in the secondary chamber first depletes. As the magnet is removed, the valve closes. Subsequently, the primary chamber replenishes the secondary chamber. This process can be repeated until the primary chamber reaches a saturation state that can no longer inflate the secondary chamber. The device could release a few microliters per actuation. Various combinations of size and thickness of primary, and secondary chambers can realize release rate of desired amount.
A miniature X-ray tube based on a carbon-nanotube electron emitter has been employed for the application to a dental radiography. The miniature X-ray tube has an outer diameter of 7 mm and a length of 47 mm. The miniature X-ray tube is operated in a negative high-voltage mode in which the X-ray target is electrically grounded. In addition, X-rays are generated only to the teeth directions using a collimator while X-rays generated to other directions are shielded. Hence, the X-ray tube can be safely inserted into a human mouth. Using the intra-oral X-ray tube, a dental radiography is demonstrated where the positions of an X-ray source and a sensor are reversed compared with a conventional dental radiography system. X-ray images of five neighboring teeth are obtained and, furthermore, both left and right molar images are achieved by a single X-ray shot of the miniature X-ray tube.
Small interfering ribonucleic acid (siRNA) cancer therapies administered by intravenous injection require a delivery system for transport from the bloodstream into the cytoplasm of diseased cells to perform the function of gene silencing. Here we describe nanosized polymeric micelles that deliver siRNA to solid tumors and elicit a therapeutic effect. Stable multifunctional micelle structures on the order of 45 nm in size formed by spontaneous self-assembly of block copolymers with siRNA. Block copolymers used for micelle formation were designed and synthesized to contain three main features: a siRNA binding segment containing thiols, a hydrophilic nonbinding segment, and a cell-surface binding peptide. Specifically, poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) comprising lysine amines modified with 2-iminothiolane (2IT) and the cyclo-Arg-Gly-Asp (cRGD) peptide on the PEG terminus was used. Modification of PEG-b-PLL with 2IT led to improved control of micelle formation and also increased stability in the blood compartment, while installation of the cRGD peptide improved biological activity. Incorporation of siRNA into stable micelle structures containing the cRGD peptide resulted in increased gene silencing ability, improved cell uptake, and broader subcellular distribution in vitro and also improved accumulation in both the tumor mass and tumor-associated blood vessels following intravenous injection into mice. Furthermore, stable and targeted micelles inhibited the growth of subcutaneous HeLa tumor models and demonstrated gene silencing in the tumor mass following treatment with antiangiogenic siRNAs. This new micellar nanomedicine could potentially expand the utility of siRNA-based therapies for cancer treatments that require intravenous injection.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)
