Two‐Wave Variable Nanotheranostic Agents for Dual‐Mode Imaging‐Guided Photo‐Induced Triple‐Therapy for Cancer

Abstract

Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA-𝜶TSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA-𝜶TSLs aggregates. The aggregation of SIA-𝜶TSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA-𝜶TSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.

Stimuli-activatable nanomedicine meets cancer theranostics

“…Under this enhanced imaging guidance, the tumor sites were irradiated with NIR light. Thermal-enhanced drug release and thermal-induced damage resulted in a high tumor inhibition rate of 79.81 ± 5.30% (Figure 12 B) 196 .…”

“…b) T2WI of SIA-αTSLs incubated with/without cathepsin B. c) Intratumoral cytokines; d) ratios of CD8 + T cells to Tregs in the tumor tissue; and e) tumor weights at the endpoint of the CT26-bearing mice after different treatments. Reproduced with permission 196 . Copyright 2022 the Authors, published by Wiley-VCH.…”

Shaping the immune‐suppressive microenvironment on tumor‐associated myeloid cells through tumor‐derived exosomes

“…Killer T cells, crucial for antitumor-specific immune responses, 95 exhibit the ability to not only cooperate with other immune cells but also directly exert an immune killing effect upon activation by tumor antigens. 96 However, TEXs directly induce apoptosis in CD8+ T cell, emerging as a significant contributor to immune suppression. 97 Research has revealed that exosomes derived from mouse head and neck tumor cell line SCCVII are rich in immunosuppressive proteins, including Fas-L, PD-L1, CD39, CD73 and COX-2.…”

“…But still some works have described actions of TEXs directly on T cells. Killer T cells, crucial for antitumor‐specific immune responses, 95 exhibit the ability to not only cooperate with other immune cells but also directly exert an immune killing effect upon activation by tumor antigens 96 . However, TEXs directly induce apoptosis in CD8+ T cell, emerging as a significant contributor to immune suppression 97 .…”

GSH-Activatable Metal-Phenolic Networks for Photothermal-Enhanced Chemotherapy and Chemodynamic Therapy

“…Photothermal therapy (PTT), utilizing photothermal agents to increase the temperature under near-infrared (NIR) light irradiation to result in cancer cell damage, has emerged as a promising approach for cancer treatment [ 14 , 15 , 16 , 17 ]. On the other hand, the increase in cancer tissue temperature can also enhance the efficiency of the Fenton catalyst, which contributes to the faster generation of highly toxic ROS for CDT [ 18 , 19 , 20 ].…”