Novel polymersomes based on Poly(2-methyl-2-oxazoline) polymers with excellent pharmacokinetic behavior and antitumor effect by modulating dynamic protein corona

The pharmacokinetic behavior of nanocarrier in vivo has been confirmed to be greatly influenced by the dynamic protein corona covered its surface, which also affects the ultimate clinical efficacy. Herein, we explored one novel polymersomes based on Poly(2-methyl-2-oxazoline) polymers (PMOXA 5 -PDBH 13 -PMOXA 5 ) with excellent drug-carrying capacity and specific protein corona manipulation. Compared to PEGylated nanoparticle (NP), the polymersomes (PC-SOM) provided a considerable advancement in therapeutic efficiency, which can selectively accumulate in tumor tissues, enhancing cellular internalization via specific proteins covering its surface such as fibronectin and moesin. Notably, in vivo antitumor effect showed that doxorubicin-loaded PC-SOM exhibited superior inhibitory rate 75.5% than 48.24% of PEGylated NP. Furthermore, through protein corona analysis we found that PC-SOM enhanced the adsorption of apolipoprotein A-I while suppressed the adsorption of complement C3 and immunoglobulin in serum from healthy volunteers and human breast cancer volunteers. These elaborated the reasons of longer circulation times and superior tumor-targeting capabilities of PC-SOM. Our work provided a promising nanoagent with novel surface-design by the dynamic protein corona for excellent pharmacokinetic behavior and antitumor effect.