Environment-stimulated nanocarriers enabling multi-active sites for high drug encapsulation as an "on demand" drug release system.

Limited active sites in polyesters hinder fabrication of multifunctional biodegradable nanocarriers for successful clinical applications. Herein, poly(malic acid) (PMA)-based biodegradable polyesters bearing large carboxyl groups in their side chains were grafted with intracellular reductive-sensitive polyethylene glycol and imidazole to construct bioreducible nanocarriers (PLM-g-ss-EGA). The uniform spherical shape and high stability of the PLM-g-ss-EGA nanocarriers were demonstrated by dynamic light scattering (DLS) and dissipative particle dynamics (DPD) simulations. Enhanced interaction between the monomers in this novel nanocarrier doubled its drug loading efficiency (15%) as compared to that of traditional polyester nanocarriers (5-7%). Moreover, stimulus-responsive assessment and in vitro drug release studies showed that these bioreducible nanocarriers can balance extracellular stability in blood circulation and intracellular "on demand" release. In vitro and in vivo assays have demonstrated that these bioreducible nanocarriers not only can substantially enhance antitumor efficacy as compared to insensitive micelles and even comparably to free DOX·HCl, but can also greatly reduce unwanted side effects in other organs. The encouraging anticancer efficiency of these poly(malic acid)-based nanocarriers opens a new avenue to design multifunctional biodegradable polyester drug-delivery systems.

Dynamic intracellular tracking nanoparticles via pH-evoked "off-on" fluorescence.

Dynamic tracking of nanoparticles in cells faces a big challenge due to fluorescence quenching. Here, the pH-switchable probe spiropyran (SP) was introduced into poly(ethylene glycol) (PEG) via atom transfer radical polymerization (ATRP) to construct expected "off-on" fluorescent nanoparticles. Strong red fluorescence was emitted to efficiently track nanoparticles in cells due to the isomerization of spiropyran to merocyanine in the endosome or lysosome.

Intracellular pH-induced fluorescence used to track nanoparticles in cells.

A nanoparticle with pH-induced fluorescence was reported for intracellular tracking. The fluorescence was evoked by the isomerization of the ring-closed form spiropyran (SP) to the ring-open form merocyanine (MC) in the weak acidic environment of cells. The SP-MC switch accelerated the dissociation of nanoparticles to trigger the release of trapped paclitaxel.

Calcitonin gene-related peptide in the pathogenesis and treatment of hypertension.

The present study demonstrated that the plasma calcitonin gene-related peptide (CGRP) concentration was lower but the CGRP content of abdominal aorta was higher in spontaneously hypertensive rats (SHR) than in normotensive rats (WKY), using specific CGRP radioimmunoassay (P less than 0.01). In eighteen patients with essential hypertension, the concentration of plasma CGRP was also much lower than that of normal subjects, suggesting that a decreased release of arterial CGRP might be a part of the pathogenesis of essential hypertension. In SHR, a significant decrease in blood pressure was found following intravenous injection of 2.5 micrograms/kg of CGRP; similarly, in seven patients with essential hypertension intravenous injection of CGRP (50 micrograms) could induce a significant hypotensive effect. These data suggest that CGRP is a new potential drug for the treatment of essential hypertension.