Hollow polydopamine spheres with removable manganese oxide nanoparticle caps for tumor microenvironment-responsive drug delivery

The development of stimuli-responsive drug delivery system has gained much attention for drug delivery. Recent studies have demonstrated that polydopamine (PDA)-based drug delivery system is capable of loading and delivering drugs, but its therapeutic efficacy has been dampened due to limited stimuli-responsiveness. In this study, a novel hybrid hollow PDA sphere was designed to deliver therapeutic agents by responding to tumor microenvironments. To overcome the limited stimuli-responsiveness in the PDA platform, manganese oxide (MnO₂) nanoparticles were employed to cap the surface of PDA hollow spheres as they exhibited potent responsiveness to endogenous Glutathione (GSH) in tumor microenvironments. Meanwhile, the GSH-sensitive MnO₂ caps can prevent drug leakage, resulting in the selective delivery of the as-loaded drug for improved antitumor effect. In addition, the outer surface of the hybrid PDA hollow sphere can be integrated with Polyethylene glycol (PEG), which facilitates the use of the novel hollow sphere for cancer therapy. Collectively, the hybrid PDA hollow sphere with removable MnO₂ nanoparticle caps is a promising vehicle to reduce drug leakage and facilitate drug release through different surroundings, providing a simple and yet effective strategy for cancer therapy.