Bioresponsive Protein Nanotherapeutics for Lung Cancer Treatment
Technical Report,01 Aug 2018,31 Jul 2019
Brigham and Womens Hospital Boston United States
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The main objective of this project is to develop a multistage nanoparticle NP platform for both effective systemic and cytosolic delivery of therapeutic proteins into tumors, and to explore the potential of this bioresponsive protein nanotherapy in lung cancer treatment. Over the past year, we have made substantial progress and accomplishments under the proposed tasks. We synthesized and characterized a library of pH-responsive polymers. The NP formation by using these polymers was evaluated by TEM and DLS. To improve the intracellular delivery of proteins, we also synthesized tetra-guanidinium saporin conjugates and tested their anti-tumor efficacy in vitro with A549 and H1299 cells. We have further evaluated the pH-responsive polymeric NPs for PTEN protein delivery in terms of cellular uptake by fluorescence imaging and flow cytometry, and PTEN expression by western blot. The pharmacokinetics of the protein NPs was also examined.
- Medicine and Medical Research