Deep NIR-II optical imaging combined with minimally invasive interventional photothermal therapy for orthotopic bladder cancer

• An excellent NIR-II PTA (HAPO-1048) for actively-targeted PTT of orthotopic BC. • Combining dual-modality 3D NIR-II PA and OCTA molecular imaging for micro-BC. • High sensitivity and specificity (about 2 mm diameter) dynamic detecting of BC. • Designing a minimally invasive interventional PTT for deep orthotopic BC. • HAPO-1048 demonstrates improved NIR-II therapeutic efficiency. Surgical resection (SR) is the major method for treating invasive or recurrent noninvasive bladder cancer (BC). However, SR still causes additional risks of urinary tract infection, bleeding and some complications that may be life-threatening. Therefore, it is of urgent medical need for new diagnosis and therapy scheme for BC. Herein, we proposed a strategy that combines dual-modality three-dimensional (3D) NIR-II photoacoustic (PA) and optical coherence tomography angiography (OCTA) molecular imaging to guide visually interventional photothermal therapy (PTT) for BC. Additionally, we developed an excellent NIR-II hyaluronic acid-IR-1048 with liposome-coated (HAPO-1048) photothermal agent for PTT of CD44 overexpressing orthotopic BC, which showed strong NIR-II optical absorption, preferable tumor targeting, excellent biocompatibility and high PTT efficacy. Combined with the NIR-II PA/PTT response of the HAPO-1048, we can achieve high sensitivity and specificity (about 2 mm diameter) dynamic monitoring and investigate the precision therapy of PTT in deep orthotopic BC (4.38 mm). Simultaneously, we can map the dynamic changes of 3D PA signals and HAPO-1048 nanoparticles (HAPO-1048 NPs) enrichment, which is closely related to the PTT efficacy. Significantly, the whole changes of complex microvascular morphometrics and angiogenesis of BC were well surveilled and assessed in vivo using OCTA. Lastly, minimally invasive interventional PTT strategy was successfully implemented to achieve a controllable and precise therapy for orthotopic BC based on laparoscopy and US guidance. In conclusion, we present a multimodal NIR-II optical imaging synergy laparoscopy interventional oncologic scheme, which should expand the current PTT technology, leading to a significant ongoing in treatment of primary tumors of urinary system.