Novel pH-responsively fluorescent biodynamers to monitor intracellular degradation of polymeric nanocarriers Justine Bassil 1,2 , Mohamed Ashraf Kamal 1,2 , Mostafa Hamed 1 , Brigitta Loretz 1 , Claus-Michael Lehr 1,2 , Sangeun Lee 1,2 and Anna Katharina Herta Hirsch 1,2 1 Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) – Helmholtz Centre for Infection Research (HZI), Campus E 8.1, 66123 Saarbrücken, Germany 2 Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany Polymeric nanocarriers are widely used in biomedical applications. While their degradation plays a crucial role in their function such as drug release, it is still challenging to track and monitor their breakdown in-situ within biological systems. [1,2] In this context, research has been directed toward molecular biodynamers. They are biopolymers polymerized by reversible dynamic covalent bonds. [3] Thus, they combine the characteristics of biopolymers (e.g. biocompatibility, biodegradability, and biofunctionality) with the feature of dynamic covalent chemistry (malleability, controllability, self-healing, adaptability, and responsiveness) leading to synergistic properties in one system. [4,5] In this study, we develop a tool to monitor polymer degradation using fluorescent de-quenching of biodynamers upon degradation under different physiological conditions. To monitor the polymer intracellular degradation, we synthesized a dynamic biodynamer activating emission upon degradation. It is composed of lysine hydrazides and BODIPY di-carboxaldehyde and is capable of undergoing pH-responsive degradation into monomers, resulting in an increase in fluorescence (Figure 1). Notably, after polymerization, the fluorescent intensity of the BODIPY monomer was quenched by 95%. Subsequent degradation under acidic conditions (10 mM phosphate buffer, pH 3) led to the release of 22% of monomers, recovering BODIPY fluorescent by 12-fold during a 72-hour incubation at 37°C. These fluorescent emission increases upon degradation and excellent biocompatibility of BODIPY-biodynamers confirmed by cell viability study established a promising starting point for further investigation of polymer degradation within biological systems. Hence, this research will provide insights into how current methods of kinetic study in polymeric nanoparticle degradation and drug release in cuvette vary from that in a cell.
Figure 1. Illustration of the dynamic polymerization of Biodynamers and Fluorescent depletion of BODIPY monomer after polymerization. References
1. M. Thambirajoo, et al., Antibiotics 2021 , 10(11), 1338. 2. P. Bawa, et al., Biomed. Mater. 2009 , 4(2), 022001. 3. Y. L iu, et al., Adv. Func. Mater. 2016 26(34), 6297–6305. 4. S. Lee, et al., Mater. Chem. Front. 2020, 4(3), 905–909. 5. S. Lee, et al ., J. Controlled Release 2023 , 353, 915–929.
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