A Brain-Targeting NIR-II Polymeric Phototheranostic Nanoplatform toward Orthotopic Drug-Resistant Glioblastoma
Xiang Su, Yi‐Sheng Liu, Yong Zhong, Ping Shangguan, Junkai Liu, Zhengqun Luo, Cai Qi, Jincheng Guo, Li Xi, Danmin Lin, Gaoyang Wang, Dong Wang, Ting Han, Jiefei Wang, Bingyang Shi, Ben Zhong Tang
Abstract
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.