Various polymer-bases nanomedicines have been developed for cancer therapy to overcome the side effects caused by the non-specific distribution of small molecular anticancer drugs in vivo. Most of nanomedicines rely on the high vascular permeability and undeveloped lymphatic system in a solid tumor (EPR effect), to demonstrate passive tumor accumulation. Zwitterionic polymers have been widely used in nanomedicines as well as biomedical applications because of their high biocompatible properties. However, a pilot molecule should be installed onto the nanomedicine bearing such zwitterionic polymers in the case of active targeting because they have no targetability against a specific cell.<br/>Amino acids are sometimes used as a pilot molecule since amino acid transporters, such as large amino acid transporters are overexpressed on many cancer cells while normal cells are not. Some nanomedicines targeting those amino acid transporters have been developed. Those amino acid-based nanomedicines consist of zwitterionic amino acids composed of the α-amine and α-carboxylic acid. The amino acid-based zwitterion gives nanomedicines biocompatibility showing no interaction with normal cells and proteins, which is just comparable to that of pMPC. In other word, polymers containing amino acid-based zwitterions in sidechains has two advantages: one is high biocompatibility given by the nature of the zwitterion, and the other is the recognition capability for amino acid transporter on cancer cells. Therefore, we designed and synthesized zwitterionic amino acid-based polymers (ZAPs) containing phenylalanine or lysine in the sidechain. We found that these ZAPs are not toxic for cells at all and able to be taken up by cancer cells via amino acid transporter mediated endocytosis. We are convinced that the biocompatibility and the cancer cell recognition capability of ZAPs will contribute to the design of nanomedicines for active targeting strategy.

Internalization into cancer cells of zwitterionic amino acid polymers via amino acid transporter recognition

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.