Nanocarriers Made of Proteins: Intracellular Visualization of a Smart Biodegradable Drug Delivery System

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2022-04, Vol.18 (15), p.e2106094-n/a
• Main Authors: Frey, Marie‐Luise, Han, Shen, Halim, Henry, Kaltbeitzel, Anke, Riedinger, Andreas, Landfester, Katharina, Lieberwirth, Ingo
• Format: Article
• Language: English
• Subjects: Biodegradability; correlative microscopy; Degradation; Drug Carriers - metabolism; drug delivery; Drug Delivery Systems; Electron microscopy; Endosomes - metabolism; Fluorescence; intracellular pathways; Lysosomes - metabolism; Microscopy; Nanocapsules; Nanoparticles; Nanotechnology; protein nanocarriers; Proteins; transmission electron microscopy
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202106094

This work analyzes the intracellular fate of protein‐based nanocarriers along their endolysosomal pathway by means of correlative light and electron microscopy methods. To unambiguously identify the nanocarriers and their degradation remnants in the cellular environment, they are labeled with fluorescent, inorganic nanoplatelets. This allows tracking the nanocarriers on their intracellular pathway by means of electron microscopy imaging. From the present data, it is possible to identify different cell compartments in which the nanocarriers are processed. Finally, three different terminal routes for the intracellular destiny of the nanocarriers are presented. These findings are important to reveal the degradation process of protein nanocapsules and contribute to the understanding of the therapeutic success of an encapsulated drug. Nanocapsules made of a protein and additionally labeled with CdSe/CdZnS nanoplatelets are examined as a model system for drug delivery. By correlating the fluorescent label with the high‐resolution electron microscopy image, the intracellular pathway of the protein nanocapsules is revealed showing the degradation of the capsule material.