Nanobiopolymer for Direct Targeting and Inhibition of EGFR Expression in Triple Negative Breast Cancer

Treatment options for triple negative breast cancer (TNBC) are generally limited to cytotoxic chemotherapy. Recently, anti-epidermal growth factor receptor (EGFR) therapy has been introduced for TNBC patients. We engineered a novel nanobioconjugate based on a poly(β-L-malic acid) (PMLA) nanoplatform for TNBC treatment. The nanobioconjugate carries anti-tumor nucleosome-specific monoclonal antibody (mAb) 2C5 to target breast cancer cells, anti-mouse transferrin receptor (TfR) antibody for drug delivery through the host endothelial system, and Morpholino antisense oligonucleotide (AON) to inhibit EGFR synthesis. The nanobioconjugates variants were: (1) P (BioPolymer) with AON, 2C5 and anti-TfR for tumor endothelial and cancer cell targeting, and EGFR suppression (P/AON/2C5/TfR), and (2) P with AON and 2C5 (P/AON/2C5). Controls included (3) P with 2C5 but without AON (P/2C5), (4) PBS, and (5) P with PEG and leucine ester (LOEt) for endosomal escape (P/mPEG/LOEt). Drugs were injected intravenously to MDA-MB-468 TNBC bearing mice. Tissue accumulation of injected nanobioconjugates labeled with Alexa Fluor 680 was examined by Xenogen IVIS 200 (live imaging) and confocal microscopy of tissue sections. Levels of EGFR, phosphorylated and total Akt in tumor samples were detected by western blotting

Public sector and circular business models : from public support towards implementation through design

In the last decade researchers interest in Sustainable Business Models has raised significantly, due to economic, social and environmental problems of the contemporary world. The philosophy and movement of Circular Economy plays an influential role therein, mainly because it provides opportunities for economic growth through environmental friendly solutions. This chapter employs literature review to further the understanding of the role public sector plays in shifting towards Circular Business Models. This work contributes to the debate on sustainable business models in several ways. It outlines the facilitating role of the public sector which aims to support private sector business models through six types of interventions. It also attempts to provide an early conceptualization of public sector circular business model. Building on that, it argues for the significant role of design in pursuing opportunities to change such business models into a more circular ones