BBB-penetrating magnetoelectric nanoparticles with sustainable Gel formulation for enhanced chemotherapy and reduced postoperative glioma recurrence

•A water-dispersible magneto-electric nanoparticle (CBPID), consisting of CoFe2O4 as magnetic core, BaTiO3 as piezoelectric shell and PEG-connected I6P8 peptide as surface coating, was designed and constructed for glioma treatment.•The magneto-electric effect could down-regulate the tight junction-associated proteins of the BBB, which synergistically with the I6P8 peptide achieved the enhanced BBB permeability and glioma targeting.•CBPID could produce mild ROS to sensitize the chemotherapy through inhibiting c-Jun N-terminal kinase (JNK) phosphorylation pathway.•CBPID could facilitate the postoperative cavity administration with magnetic adsorption immobilization for the repeated magnetoelectric-activated therapy to inhibit postoperative recurrence of glioma.•CBPID could be mostly excreted through feces without causing of obvious blood and major organ abnormalities, and even improve the behavioral abnormalities caused by glioma. Overcoming blood–brain barrier (BBB), reducing drug resistance and inhibiting postoperative recurrence are the huge challenges of glioma treatment. Herein, a magnetoelectric nanoparticle, applying CoFe2O4 as magnetic core, BaTiO3 as piezoelectric shell and polyethylene glycol-connected I6P8 peptide as surface coating (CBPI), was used for glioma-targeted treatment. This nanoparticle could down-regulate tight junction proteins of BBB via magnetoelectric effect, synergized with I6P8 peptide, to achieve the enhanced BBB permeability and glioma targeting. Under magnetic field activation, this nanoparticle, after doxorubicin loading to formulate CBPID, could accomplish magnetoelectricity and pH-responsive drug release, and generate mild reactive oxygen species to sensitize the chemotherapy through c-Jun N-terminal kinase phosphorylation pathway. Importantly, CBPID facilitated intraoperative cavity administration with magnetic immobilization after easy doping to Surgiflo filler, benefiting the repeated magnetoelectric-activated therapy to inhibit glioma postoperative recurrence. Moreover, CBPID could be mostly excreted through feces after intravenous injection, which did not cause obvious blood and organ abnormalities and even improved the behavioral abnormalities caused by glioma.