Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking.

The slowly activating delayed rectifier K+ current (IKs) plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and ß-subunit encoded by KCNE1. Evidence suggested that IKs was regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed to identify the specific PKC isoform involved in the long-term regulation of IKs current. The IKs current was recorded using whole-cell patch-clamp technique in human embryonic kidney (HEK) 293B cell co-transfected with human KCNQ1/KCNE1 genes. The results revealed that both chronic activation of Ang II and PMA reduced the IKs current in a long-term regulation (about 24 hours). Further evidence showed that PKCε knockdown by siRNA antagonized the AngII-induced chronic inhibition on the IKs current, whereas knockdown of cPKC (PKCα and PKCß) attenuated the inhibition effect of PMA on the current. Moreover, the forward transport inhibition of the channel with brefeldin A alleviated the Ang II-induced chronic inhibition on IKs current, while the channel endocytosis inhibition with dynasore alleviated both Ang II and PMA-induced chronic inhibition on IKs current. The above results showed that PKCε activation promoted the channel endocytosis and inhibited the channel forward transport to the plasma membrane, while cPKC activation only promoted the channel endocytosis, which both down regulated the channel current.