A Brain-Targeting NIR-II Polymeric Phototheranostic Nanoplatform toward Orthotopic Drug-Resistant Glioblastoma

Glioblastoma is the most common and devastating brain tumor owing to its high invasiveness and high-frequency drug resistance. Near infrared-II (NIR-II) imaging-guided phototherapy based on polymer luminogens provides a promising remedy against drug-resistant glioma, but it is difficult to maximize photoenergy utilization. Herein, we designed a series of semiconducting polymers to boost the visualization and ablation of glioblastoma. By subtly engineering the side chains or substituents on the phenothiazine and thiophene moieties, an NIR-II polymer luminogen with high-quality fluorescence performance, good solubility, superior photothermal conversion, and balanced reactive oxygen species generation is achieved. The optimal polymer possesses a branched alkyl chain and tetraphenylethylene pendant to manipulate the equilibrium between the radiative and nonradiative energy-dissipating channels. High-sensitivity NIR-II imaging was used to monitor the blood-brain barrier penetration and glioma cell targeting of apolipoprotein E-modified polymer nanoparticles. The NIR irradiation triggers and maximizes the photon utilization in prominent photodynamic/photothermal synergistic therapy in orthotopic drug-resistant glioblastoma.