Source Datas

All of the different PEGylation levels SN38 prodrug nanoparticles exhibited high drug loading (>25%) but distinct behaviors depending on PEGylation level. Low PEGylation (20%) led to poor colloidal stability, reduced cellular uptake, and rapid mononuclear phagocyte system (MPS) clearance, resulting in unfavorable pharmacokinetics. Moderate PEGylation (80%) improved in vitro stability and uptake but remained insufficient to prevent rapid clearance in vivo. In contrast, high PEGylation (150%) significantly enhanced pharmacokinetic profiles, prolonged circulation, and increased tumor accumulation. These nanoparticles also showed superior antitumor efficacy without triggering anti-PEG immune responses or accelerated blood clearance (ABC) effects. Although high PEGylation slightly reduced cellular uptake, it conferred essential stability for systemic delivery, improving in vivo therapeutic outcomes.