Polysarcosine as PEG Alternative for Enhanced Camptothecin-Induced Cancer Immunogenic Cell Death

Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.