Red cell membrane camouflaged PLGA nanoparticles loading with Bufotalin and Niraparib for synergistic therapy of ovarian cancer

• A multifunctional nano-platform integrating targeting, long-circulation, and drug release. • Establishing a dual-intervention mechanism via “DNA repair blockade and oxidative attack” • Achieving comprehensive anti-tumor efficacy: treatment, anti-recurrence, and anti-metastasis. The poly (ADP-ribose) polymerase (PARP) inhibitor of Niraparib played an important role in the maintenance treatment of ovarian cancer, but it still failed to significantly improve the survival rate of ovarian cancer patients. Thus, it is urgent to develop new strategies to address this challenge. Considering that Bufotalin can efficiently induce reactive oxygen species and suppress DNA damage repair, the key determinants suppressing ovarian cancer growth and metastasis, the combination of Niraparib and Bufotalin was adopted to develop poly (lactic-co-glycolic acid) nanoparticles based nanodrug. Cell membrane coating and surface conjugation of an ovarian cancer-specific aptamer were used to endow tumor cell targeting capability. In vitro results demonstrated that this nanoplatform efficiently induced reactive oxygen species and activated caspase-3-dependent apoptosis (more than 55.5%). Concurrently, the PARP inhibitory effect, resulting in 22.1% protein downregulation, amplified DNA damage through a dual mechanism of “repair blockade–oxidative attack”, directly inhibiting DNA repair while inducing genomic instability. In vivo results revealed that the concentration of nanodrug in the tumor tissue increased 3.2-fold, compared to free drugs. The inhibition rate of tumor growth and metastasis reached 64.5% and 72.7%, respectively. In summary, this nanodrug provided an alternative for inhibiting ovarian cancer recurrence and metastasis.