Ivan Kempson - Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour

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      Publication Details (including relevant citation   information):

      Tseng, S.-J., Liao, Z.-X., Kao, S.-H., Zeng, Y.-F., Huang, K.-Y.,   Li, H.-J., Yang, C.-L., Deng, Y.-F., Huang, C.-F., Yang, S.-C.,   Yang, P.-C., Kempson, I.M.  Nature Communications, 6, 6456,   doi:10.1038/ncomms7456

      Abstract:

      Anticancer therapies are often compromised by nonspecific effects   and challenged by tumour environments’ inherent physicochemical   and biological characteristics. Often, therapeutic effect can be   increased by addressing multiple parameters simultaneously. Here   we report on exploiting extravasation due to inherent vascular   leakiness for the delivery of a pH-sensitive polymer carrier.   Tumours’ acidic microenvironment instigates a charge reversal   that promotes cellular internalization where endosomes   destabilize and gene delivery is achieved. We assess our carrier   with an aggressive non-small cell lung carcinoma (NSCLC) in   vivo model and achieve >30% transfection efficiency via   systemic delivery. Rejuvenation of the p53 apoptotic pathway as well   as expression of KillerRed protein for sensitization in   photodynamic therapy (PDT) is accomplished. A single   administration greatly suppresses tumour growth and extends   median animal survival from 28 days in control subjects to 68   days. The carrier has capacity for multiple payloads for greater   therapeutic response where inter-individual variability can   compromise efficacy.

      Address (URL): http://www.nature.com/ncomms/2015/150305/ncomms7456/full/ncomms7456.html