Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

Abstract

Phototheranostic agents in the second near‐infrared (NIR‐II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR‐II nanoagents for imaging‐guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR‐II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low‐bandgap D‐A π‐conjugated polymer (DPP‐BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR‐II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail‐vein intravenous injection of tumor‐bearing mice, Pdots also show high‐efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm−2, which is much lower than its maximum permissible exposure limit of 1 W cm−2. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.

Activatable NIR‐II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy

“…e) Calculation of the photothermal conversion efficiency at 1064 nm. f) Comparison of photothermal conversion efficiency (η) of reported PTT agents in the NIR‐II biowindow: 1) AuNCs@SiO 2 ; 2) Au 3 Cu@PEG TPNCs; [ 46 ] 3) Au‐wires‐on‐AuNR; [ 47 ] 4) Pt Spiral; [ 48 ] 5) Cu 2 MnS 2 NPs; [ 49 ] 6) Nb 2 C (Mxene); [ 50 ] 7) Cu 3 BiS 3 NRs; [ 51 ] 8) L‐Pdots; [ 52 ] 9) TBDOPV‐DT NPs; [ 53 ] 10) SPN‐DT. [ 54 ] g) Relative viabilities of 4T1 cells after co‐incubation with different concentrations of AuNCs@SiO 2 under different 1064 nm laser treatment (0.5 W cm −2 ).…”

Photoacoustic Imaging and Photothermal Therapy of Semiconducting Polymer Nanoparticles: Signal Amplification and Second Near‐Infrared Construction

“…The blood routine indexes including white blood cells, red blood cells, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean platelet volume of SPN‐treated mice are not significantly different than that observed in control mice, suggesting the biosafety of SPNs in mice. [ 61 ] However, long‐term (longer than 14 days) safety studies have not been reported, which is important for clinical applications of promising SPNs. The development of SPNs with renal clearance or biodegradation capability is an option to accelerate the clearance of SPNs from the body.…”

“…To investigate this issue, Yuan and co‐workers fabricated an ultrasmall SPN (SPN37‐S) based on a novel SP (SP37), Poly([2,5‐bis(2‐decyltetradecyl)‐2,5‐dihydropyrrolo[3,4‐c]pyrrole‐1,4‐dione‐3,6‐dithienyl]‐ co ‐[6‐(2‐ethylhexyl)‐[1,2,5]thiadiazolo[3,4‐f]benzotriazole‐4,8‐diyl]), to compare the tumor accumulation ability with large SPN (SPN37‐L). [ 61 ] SPN37‐L was obtained via a normal nanoprecipitation method with the assistance of poly(styrene‐ co ‐maleic anhydride) (PSMA). A modified nanoprecipitation method was fabricated to obtain SPN37‐S.…”

Organic semiconducting nanomaterials‐assisted phototheranostics in near‐infrared‐II biological window

“…In addition, OSPs-or OSOs-based OSNs have excellent light-capturing capability, strong photostability, good biocompatibility, and design flexibility, which make them good candidates for NIR-II PAI-guided PTT. To date, OSPs that have strong NIR-II absorption profile are mainly focused on BBT-, thiadiazolobenzotriazole-, thiadiazoloquinoxaline-, and thiophene-fused benzodifurandione-based oligo (pphenylenevinylene)-based skeleton structures, 43,[64][65][66] and their in vivo phototheranostics were widely investigated. Fan et al designed a series of semiconducting polymer nanoparticles (SPNs) with absorption beyond 1000 nm for efficient PAI-guided PTT in the NIR-II window.…”

“…To address this issue, Yuan's group reported a metabolizable semiconducting polymer dots (Pdots) for NIR-II phototheranostic. 66 In this study, ultrasmall Pdots (S-Pdots) with average diameter of 4 nm were fabricated via a modified nanoprecipitation method. The as-prepared Pdots showed excellent photothermal performance with a high PCE of 53.1%, guarantying their anticancer capability.…”