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Photo-chemotherapy is a potent anticancer therapeutic approach. Herein, we designed a gold-capsulated lapatinib nanomedicine for breast cancer treatment. The biodegradable PLGA (poly (lactic-co-glycolic acid)) nanoparticles were surface coated with glycol chitosan followed by adsorption and reduction of gold seeds on the surface to form nanocapsule. These multifunctional nanomaterials exhibited significant absorbance (600–900 nm) in the near-infrared region and had a porous surface that facilitated controlled diffusion of the encapsulated anticancer drug, lapatinib. Further, the gold-coated PLGA lapatinib nanocapsule showed synergistic effect of combined chemo-photothermal therapy with > 80% cytotoxicity. Moreover, these nanomaterials were found to be non-hemolytic and biocompatible. The biodistribution of the nanocapsule in Balb/c mice revealed higher Au content in the liver followed by spleen with no significant change in body weight and abnormal clinical signs. Hence, gold-capsuled polymeric nanomedicine could be a promising therapeutic agent. [ABSTRACT FROM AUTHOR]

Striatal neurons depends on an afferent supply of brain-derived neurotrophic factor-(BDNF) that explicitly interacts with tropomyosin receptor kinase B (TrkB) receptor and performs sundry functions including synaptic plasticity, neuronal differentiation and growth. Therefore, we aimed to scrutinize an active molecule that functions identical to BDNF in activating TrkB receptor and it's downstream targets for restoring neuronal survival in Huntington disease (HD). Data from in vitro Neuro-2a cell line showed that treatment with 7,8-dihydroxyflavone (7,8-DHF), improved 3-nitropropionic acid (3-NP) induced neuronal death by stabilizing the loss of mitochondrial membrane potential and transiently increased the activity of cAMP-response element-binding protein (CREB) and BDNF via TrkB receptor activation. Consistent with in vitro findings, our in vivo results stated that treatment with 7,8-DHF at a dose of 10 mg/kg body weight ameliorated various behavior alterations caused by 3-NP intoxication. Further histopathological and electron microscopy evidences from striatal region of 3-NP mice brain treated with 7,8-DHF showed more improved neurons with intact mitochondria and less autophagic vacuoles. Protein expression analysis of both in vitro and in vivo study showed that 7,8-DHF promotes neuronal survival through upregulation and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt at serine-473/threonine-308). Akt phosphorylation additionally phosphorylates Bad at serine-136 and inhibits its translocation to mitochondria thereby promoting mitochondrial biogenesis, enhanced ATP production and inhibit apoptosis mediated neuronal death. These aforementioned findings help in strengthening our hypothesis and has come up with a novel neuroprotective mechanism of 7,8-DHF against 3-NP induced neuronal death. [ABSTRACT FROM AUTHOR]