Antibody Polymer Conjugates (APCs) for Active Targeted Therapeutic Delivery.
Pintu KanjilalKhushboo SinghRitam DasJoseph MatteSankaran ThayumanavanPublished in: Biomacromolecules (2023)
Antibody drug conjugates (ADCs) are poised to have an enormous impact on targeted nanomedicine, especially in many cancer pathologies. The reach of the current format of ADCs is limited by their low drug-to-antibody ratio (DAR) because of the associated physiochemical instabilities. Here, we design antibody polymer conjugates (APCs) as a modular strategy to utilize polymers to address ADC's shortcomings. We show here that conjugation of polymer-based therapeutic molecules to antibodies helps increase the DAR, owing to the hydrophilic comonomer in the polymer that helps in masking the increased hydrophobicity caused by high drug loading. We show that the platform exhibits cell targetability and selective cell killing in multiple cell lines expressing disease-relevant antigens, viz ., HER2 and EGFR. The ability to use different functionalities in the drug as the handle for polymer attachment further demonstrates the platform nature of APCs. The findings here could serve as an alternative design strategy for the next generation of active targeted nanomedicine.
Keyphrases
- cancer therapy
- drug delivery
- single cell
- small cell lung cancer
- high throughput
- cell therapy
- computed tomography
- papillary thyroid
- emergency department
- epidermal growth factor receptor
- stem cells
- adverse drug
- dendritic cells
- drug induced
- mesenchymal stem cells
- magnetic resonance
- diffusion weighted imaging
- solid phase extraction
- simultaneous determination