Photoacoustic mediated multifunctional tumor antigen trapping nanoparticles inhibit the recurrence and metastasis of ovarian cancer by enhancing tumor immunogenicity

Abstract

The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from “cold tumor” to “hot tumor” that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.

Combined Cancer Immunotheranostic Nanomedicines: Delivery Technologies and Therapeutic Outcomes

“…Employing MIA-PaCa-2-treated cells, the Ce6-R-Exo group's PA signal was 9.0 and 5.5 times higher than the controls as well as Ce6liposome groups, suggesting that compared to liposomal administration distribution of Ce6 through exosomes to tumor cells was much more significant, leading to a stronger PA signal for management of pancreatic cancer. 24 Zhong et al 25 developed a multipurpose antigen-caging nanoparticle made of poly(lactic-co-glycolic acid) and oxygencarrying perfluoropentane (PFP) loaded with ICG, aluminum hydroxide (Al(OH) 3 ), an adjuvant approved by the FDA, and oxaliplatin (PPIAO) to increase antigen presentation and to set up an inflammatory microenvironment. The PPIAO-phagocytosis rate of ID8 mouse ovarian tumor cells was 96.3%, and there was a rise in intracellular ROS owing to oxygen-carrying PFP after 808 nm laser and ultrasonic irradiation, which also triggered the total apoptotic cell death of 95.71%.…”

“…In an ovarian tumor model, a PA-mediated PPIAO NP combined treatment increased tumor the temperature (55 °C during the treatment by thermal infrared imaging), which encouraged greater CD8+ T cell stimulation in vivo and effectively reduced primary (65%) and metastatic (50%) tumor development. 25 As an example of immunostimulation through ICD, Chen et al 26 reported a PEGylated antimony (Sb) nanopolyhedron system using a typical group VA semimetal antimony, for plasmonic PTT. An effective ligand-guided growth approach for manufacturing Sb nanopolyhedrons (Sb NPHs) with high photothermal conversion efficiency, great biocompatibility, and PTT durability was used.…”

“…CRT and HMGB-1-expressing ID8 cells were identified following PPIAO treatment. In an ovarian tumor model, a PA-mediated PPIAO NP combined treatment increased tumor the temperature (55 °C during the treatment by thermal infrared imaging), which encouraged greater CD8+ T cell stimulation in vivo and effectively reduced primary (65%) and metastatic (50%) tumor development …”

“…Zhong et al 25 developed a multipurpose antigen-caging nanoparticle made of poly(lactic- co -glycolic acid) and oxygen-carrying perfluoropentane (PFP) loaded with ICG, aluminum hydroxide (Al(OH) 3 ), an adjuvant approved by the FDA, and oxaliplatin (PPIAO) to increase antigen presentation and to set up an inflammatory microenvironment. The PPIAO-phagocytosis rate of ID8 mouse ovarian tumor cells was 96.3%, and there was a rise in intracellular ROS owing to oxygen-carrying PFP after 808 nm laser and ultrasonic irradiation, which also triggered the total apoptotic cell death of 95.71%.…”

Nanotechnology‐enhanced radiotherapy and the abscopal effect: Current status and challenges of nanomaterial‐based radio‐immunotherapy

“…There have also been reports of other types of non-PEGylated ACNPs, such as those made of natural polysaccharides (Guibin Pang et al, 2019). PEGylated PLGA NPs loaded with Al(OH) 3 nanoclusters (NCs) have also been explored as ACNPs (Zhong et al, 2022). Al(OH) 3 NCs capture antigens via electrostatic, hydrophobic as well as metal-ligand exchange interactions.…”