Chloride ion, a pivotal cerebral anion involved in neuronal inhibition, is implicated in various neurodegenerative diseases. Conventional direct faradaic detection based on electron transfers at solid electrode/solution interfaces has been proven ineffective due to the electrochemically inactive nature of Cl−. Here, we present an approach involving molecularly tailored liquid/liquid interfacial ultramicro iontronics (L/L-UIs) supported at ultramicropipettes filled with organic gel containing lipophilic bis-thioureas ionophores, which represents the first application of amperometric methodology based on electrochemical facilitated ion transfers reactions at a soft L/L ultramicrointerface to achieve in vivo sensing of electrochemically inactive ions, and dynamically tracking cerebral Cl− in vivo. Furthermore, evidence of dynamic neuronal Cl− regulation via KCC2 modulated through GABAB receptors was provided, further substantiating GABAB receptor–mediated Cl−-related neuronal inhibition. The proposed L/L-UIs have notable potential for in situ tracking of other crucial electrochemically inactive ions or ionized biomolecules in vivo, thereby facilitating the study of brain diseases and the diagnosis and treatment of related disorders.
Suhui Ni,Yun Liu,Yue Tang,Jing Chen,Shuhan Li,Ji Pu,Lidong Han
The effect of gene silencing by survivin siRNA (siSurvivin) on the proliferation and apoptosis of lung tumor has been attracted more interest. GABA B receptor ligand-directed nanoparticles consisting of baclofen functionalized trimethyl chitosan (Bac-TMC) as polymeric carriers, tripolyphosphate (TPP) as ionic crosslinker, and siSurvivin as therapeutic genes, were designed to enhance the survivin gene silencing. GABA B receptor agonist baclofen (Bac) was initially introduced into TMC as a novel ligand. This Bac-TMC/TPP nanoparticles increased the uptake of survivin siRNA through the interaction with GABA B receptor, further resulted in efficient cell apoptosis and gene silencing. For siRNA-loaded nanoparticles pulmonary delivery, mannitol was utilized for it delivery into pressurized metered dose inhalers (pMDI). The fine particle fractions of this formulation was (45.39 ± 2.99)% indicating the appropriate deep lung deposition. These results revealed that this pMDI formulation containing Bac-TMC/TPP nanoparticles would be a promising siRNA delivery system for lung cancer treatment.