Assembly of pH-Responsive Antibody-Drug-Inspired Conjugates.
Marco RaabeAstrid Johanna HeckSiska FührerDominik SchauenburgMichaela PieszkaTao WangMaksymilian Marek ZegotaLutz NuhnDavid Yuen Wah NgSeah Ling KuanTanja WeilPublished in: Macromolecular bioscience (2021)
With the advent of chemical strategies that allow the design of smart bioconjugates, peptide- and protein-drug conjugates are emerging as highly efficient therapeutics to overcome limitations of conventional treatment, as exemplified by antibody-drug conjugates (ADCs). While targeting peptides serve similar roles as antibodies to recognize overexpressed receptors on diseased cell surfaces, peptide-drug conjugates suffer from poor stability and bioavailability due to their low molecular weights. Through a combination of a supramolecular protein-based assembly platform and a pH-responsive linker, the authors devise herein the convenient assembly of a trivalent protein-drug conjugate. The conjugate should ideally possess distinct features of ADCs such as 1) recognition sites that recognize cell receptor and are arranged on 2) distinct locations on a high molecular weight protein scaffold, 3) a stimuli-responsive linker, as well as 4) an attached payload such as a drug molecule. These AD-like conjugates target cancer cells that overexpress somatostatin receptors, can enable controlled release in the microenvironment of cancer cells through a new pH-responsive biotin linker, and exhibit stability in biological media.
Keyphrases
- cancer therapy
- highly efficient
- amino acid
- protein protein
- drug delivery
- single cell
- cell therapy
- binding protein
- stem cells
- small molecule
- adverse drug
- high throughput
- emergency department
- staphylococcus aureus
- biofilm formation
- quantum dots
- candida albicans
- neuroendocrine tumors
- electronic health record
- smoking cessation