PhD defence by Clara Coll Satué

On Monday 27 May, Clara Coll Satué will defend her PhD thesis "Towards the development of multifaceted oxygen carriers encapsulating high concentrations of fully functional hemoglobin".

Time: 13:30

Place: Building 421, auditorium 71

Supervisor: Associate Professor Leticia Hosta-Rigau

Co-supervisor: Associate Professor Johan Ulrik Lind

Assessment committee:
Associate Professor Line Hagner Nielsen, DTU Health Tech

Associate Professor Lene Jørgensen, University of Copenhagen

Professor Leif Bülow, University of Lund

Chairperson:
Associate Professor Yi Sun, DTU Health Tech

Abstract:
Oxygen, which is crucial for our life, is mainly transported by hemoglobin (Hb) within our red blood cells. Any condition involving blood loss or impaired Hb function can lead to devastating consequences. While blood transfusions are the go-to life-saving procedure in medical practice, they face limitations such as availability and compatibility issues. Hb-based oxygen carriers (HBOCs) emerge as promising alternatives, yet challenges persist in developing safe and effective HBOCs.

This thesis delves into some of the difficulties encountered in the development of HBOCs, aiming to create multifaceted HBOCs using encapsulation strategies that are able to entrap high concentrations of Hb while preserving its functionality. Through exhaustive exploration of both polymeric and metal organic framework-based platforms, particularly PLGA and ZIF-8- based nanoparticles (NPs), remarkable results were achieved. Hb@ZIF-8 NPs were synthesized using a facile, rapid, and green protocol. The incorporation of polyethylene glycol (PEG) allowed to obtain Hb@ZIF-8 NPs with an impressive drug loading of 99% while preserving 95% of Hb´s functionality, surpassing previous studies. In addition, the thorough screening revealed the delicate balance between preserving crystalline structure vs maintaining high Hb content and functionality, establishing the guidelines to synthesize ZIF-8 based HBOCs with tailored properties. Then, the Hb@ZIF-8 NPs were surface coated with metal phenolic networks (MPNs) and PEG. MPNs improved their stability, broadening their biomedical application and conferring them with antioxidant properties to minimize the conversion of Hb into non-functional metHb. PEGylation reduced IgG adsorption and increased bovine serum albumin adsorption, potentially extending their circulation time. Additionally, alternative coatings with human serum albumin showed promising biocompatibility and efficient oxygen delivery, as demonstrated in vessel-on-chip models under hypoxic conditions.

All in all, this thesis presents various multifaceted HBOCs, contributing to moving forward a new generation of HBOCs that more closely mimic our RBCs and aim to restore tissue oxygenation in emergency situations.