pH-responsive nanoparticles based on optimized synthetic amphiphilic poly(β-amino esters) for doxorubicin delivery

Synthesis of amphiphilic poly(β-amino esters) (PBAE) was optimized by stepwise feeding of monomers (PBAE-(P-H)) compared with one-pot synthesis (PBAE-(P&H)) based on poly(ethylene glycol) diacrylate (PEGDA) and 1,6-hexanediol diacrylate (HDDA). Interestingly, optimized synthetic PBAE-(P-H) had smaller critical micelle concentration (CMC) of 6.6 μg/mL on average than one-pot synthetic PBAE-(P&H) (10.4 μg/mL). Nanoparticles were prepared based on PBAE-(P-H) and PBAE-(P&H), respectively. PBAE-(P-H) nanoparticles exhibited more narrow size distribution (average size, 105.3 nm; PDI, 0.103) than PBAE-(P&H) nanoparticles (average size, 117.8 nm; PDI, 0.233) demonstrated by dynamic light scattering and transmission electron microscopy. Afterward, PBAE-(P-H) and PBAE-(P&H) nanoparticles were selected to further investigate the properties including charge conversion and pH responsiveness. Doxorubicin (DOX) was encapsulated into nanoparticles. DOX release in vitro was enhanced as the decrease of pH value. Furthermore, DOX-loaded PBAE-(P-H) and PBAE-(P&H) nanoparticles exhibited enhanced cytotoxicity and cellular uptake against HCT116 cells compared with DOX under tumor microenvironment.