Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy

The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers. Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. Currently, approaches for restoration of TP53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, we introduced an endogenous nanoplatform to effectively deliver the TP53 protein. Briefly speaking, the endogenous TP53 proteins were fused by the Lamp2b and loaded into extracellular vesicles-based nanoparticles, which could markedly restore the TP53 expression in natural TP53-deficient ovarian cancer (OCs) and subsequently inhibit cell proliferation as well as induce cell apoptosis. Moreover, a well-known biotin streptavidin binding strategy was used to confer the nanoplatform targeting ability. Since mesothelin (MSLN) expressed highly in ovarian cancer, the anti-MSLN nanoplatform were engineered to deliver TP53 proteins to MSLN ovarian cancer and exert the anti-tumor ability. Our findings indicated that restoration of tumor suppressors by the targeting nanoplatform could be promising nanotechnology approaches for potential ovarian cancer treatment.