Multimodal Imaging‐Guided Photothermal Immunotherapy Based on a Versatile NIR‐II Aggregation‐Induced Emission Luminogen

Abstract

Synergistic photothermal immunotherapy has captured great attention owing to the mutually strengthening therapeutic outcomes towards both original tumors and abscopal tumors. Herein, a versatile theranostic agent displaying aggregation‐induced emission, namely TPA‐BT‐DPTQ, was designed and prepared based on benzo[c]thiophene unit as a building block; it can be used for simultaneous fluorescence imaging (FLI) in the second near‐infrared (NIR‐II) window, photoacoustic imaging (PAI), photothermal imaging (PTI), and thermal eradication of tumors. Further experiments validate that photothermal therapy (PTT) mediated by TPA‐BT‐DPTQ nanoparticles not only destroys the primary tumor but also enhances immunogenicity for further suppressing the growth of tumors at distant sites. Furthermore, PTT combining a programmed death‐ligand 1 (PD‐L1) antibody prevents the metastasis and recurrence of cancer by potentiating the effect of immunotherapy.

A Versatile 980 nm Absorbing Aggregation‐Induced Emission Luminogen for NIR‐II Imaging‐Guided Synergistic Photo‐Immunotherapy Against Advanced Pancreatic Cancer

“…In this contribution, a versatile NIR-II excitable PTA, TPE-BT-BBTD, was delicately designed and synthesized by recommending benzo[c]thiophene as a key building unit. [39,40] The fabricated TPE-BT-BBTD nanoparticles (NPs) with the longest absorption wavelength among the reported AIEgens were successfully employed for deep NIR-II FLI guided PTT against pancreatic cancer. Simultaneously, αPD-L1, an immune checkpoint inhibitor and tumor-targeted molecular, was linked to TPE-BT-BBTD NPs to fabricate αPD-L1@TPE-BT-BBTD NPs for immunosuppression reversal, targeted tumor damage, and metastasis prevention.…”

An acceptor-shielding strategy of photosensitizers for enhancing the generation efficiency of type I reactive oxygen species and the related photodynamic immunotherapy

“…During the process of ROS generation, 35 as shown in Scheme 1B, the PS molecule with AIE characteristics is excited by absorbing a photon of light into the 1 PS*, and it is very unstable and must lose its excess energy either as the emission of light (fluorescence) or may likely undergo a process known as ISC to form a more stable 3 PS* because the route of IC (nonradiative channel may produce heat) is restricted by taking advantage of AIE PSs. 31,36 A photochemical process can occur wherein the 3 PS* undergoes one electron transfer step to produce ˙PS − . Electron transfer from ˙PS − to O 2 results in the generation of ˙O 2 − , which can dismutate or decrease to yield H 2 O 2 , and H 2 O 2 can further react with ˙PS − , forming ˙OH and releasing O 2 .…”

“…Reducing the energy level between the singlet and triplet states (ΔE st ) is a general method for enhancing triplet energy production by constructing a strong intramolecular charge transfer (ICT) state by using electron-rich donor (D) and electron-deficient acceptor (A) chemical structures. [29][30][31] Third, the lifetime of T 1 is sufficiently long to ensure electron transfer from the excited singlet PS ( 1 PS*) to the long-lasting excited triplet state PS ( 3 PS*) and then generation of a radical anion of PS ( • PS − ). Moreover, there is no unnecessary side reaction during these transformations; that is, the environment of PS* needs to be protected to accomplish these rapid electron transfer processes.…”

“…During the process of ROS generation, 35 as shown in Scheme 1B, the PS molecule with AIE characteristics is excited by absorbing a photon of light into the 1 PS*, and it is very unstable and must lose its excess energy either as the emission of light (fluorescence) or may likely undergo a process known as ISC to form a more stable 3 PS* because the route of IC (nonradiative channel may produce heat) is restricted by taking advantage of AIE PSs. 31,36 A photochemical process can occur wherein the 3…”

AIEgen-Peptide Bioprobes for the Imaging of Organelles

“…In the aggregated state, molecular rotor movement is restricted, and excitation energy is mainly released through radiative transitions, which results in the bright and stable fluorescence emission [ 25 , 26 , 27 ]. In recent years, due to their outstanding properties, such as a high quantum yield, a resistance to photobleaching, a large Stokes shift and photosensitivity, AIEgens have been widely used in biomarker detection and imaging [ 28 , 29 ], drug delivery [ 30 , 31 ], surgery navigation [ 32 , 33 ], anti-bacteria processes [ 34 ], phototherapy [ 35 , 36 , 37 , 38 , 39 , 40 ] and a series of biomedical application areas.…”