Co-assembly of FeTPP@Fe_(3)O_(4) nanoparticles with photo-enhanced catalytic activity for synergistic tumor therapy

Chemodynamic therapy(CDT)offers a promising alternative to conventional cancer treatment.However,the limited acidity and H_(2)O_(2) concentration in tumor microenvironment(TME)severely impair the anticancer effects of CDT.In this study,we report a microemulsion-assisted coassembly method to prepare iron(III)tetraphenylporphyrin(FeTPP)and magnetic(Fe_(3)O_(4))nanocomposite material(FeTPP@Fe_(3)O_(4)),using photoactive FeTPP and Fe_(3)O_(4) nanocrystals as building blocks.The selfassembling nature of FeTPP results in disordered aggregation and fluorescence quenching,leading to a high light-to-heat conversion efficiency.Continuously,the photo-thermal effect enhances the catalytic decomposition of hydrogen peroxide(H_(2)O_(2))in the Fenton reaction on Fe_(3)O_(4) nanocrystals to generate highly toxic hydroxyl radicals(·OH)to destroy cancer cells.This cascade reaction produces a synergistic therapeutic effect between CDT and photothermal therapy(PTT),which significantly amplifies the therapeutic effect and enhances the treatment outcome of cancer patients.The highly efficient tumor catalytic therapy in vivo results confirmed that this nanomedicine treatment is an excellent biocompatible catalytic nanomedicine therapy achieved through a photo-enhanced Fenton reaction activity approach.

Brain-targeted polymersome codelivery of siRNA and temozolomide for effective glioblastoma chemo-RNAi synergistic therapy

Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yields unsatisfactory therapeutic effects. Small interfering RNA (siRNA) is a potential alteration tool for sensitivity of TMZ by targeting DNA repair enzymes. However, a suitable TMZ and siRNA codelivery system that can effectively and actively co-deliver siRNA/TMZ into the brain tumor is lacking. In this study, we constructed an angiopep-2 decorated polymersomal delivery system to co-deliver TMZ/siRNA for synergistic GBM therapy. This targeted polymersomal nanomedicine not only enhanced the circulation time of siRNA/TMZ in blood but also improved their blood-brain barrier (BBB) crossing and GBM targeting ability. Moreover, when we co-administered siRNAs specific to retinoblastoma binding protein 4 (RBBP4) together with TMZ in GBM cells, these RBBP4- specific siRNA (siRBBP4) modulated the sensitivity of TMZ by regulating MGMT, and thus showed a powerful synergistic anti-tumor effect. We demonstrated that angiopep-2 decorated polymersomal siRBBP4/TMZ co-loaded nanomedicines are capable of inhibiting tumor growth and significantly improved life expectancy of orthotropic GBM bearing mice. Overall, our study suggests that such a polymersomal TMZ/siRNA codelivery system provides a robust and potent nanoplatform for targeted GBM chemo-RNAi therapy.