Sequential PDT and PTT Using Dual‐Modal Single‐Walled Carbon Nanohorns Synergistically Promote Systemic Immune Responses against Tumor Metastasis and Relapse

Abstract

Immune responses stimulated by photodynamic therapy (PDT) and photothermal therapy (PTT) are a promising strategy for the treatment of advanced cancer. However, the antitumor efficacy by PDT or PTT alone is less potent and unsustainable against cancer metastasis and relapse. In this study, Gd 3+ and chlorin e6 loaded single‐walled carbon nanohorns (Gd‐Ce6@SWNHs) are developed, and it is demonstrated that they are a strong immune adjuvant, and have high tumor targeting and penetration efficiency. Then, three in vivo mouse cancer models are established, and it is found that sequential PDT and PTT using Gd‐Ce6@SWNHs synergistically promotes systemic antitumor immune responses, where PTT stimulates dendritic cells (DCs) to secrete IL‐6 and TNF‐ α , while PDT triggers upregulation of IFN‐ γ and CD80. Moreover, migration of Gd‐Ce6@SWNHs from the targeted tumors to tumor‐draining lymph nodes sustainably activates the DCs to generate a durable immune response, which eventually eliminates the distant metastases without using additional therapeutics. Gd‐Ce6@SWNHs intervened phototherapies also generate durable and long‐term memory immune responses to tolerate and prevent cancer rechallenge. Therefore, this study demonstrates that sequential PDT and PTT using Gd‐Ce6@SWNHs under moderate conditions elicits cooperative and long‐lasting antitumor immune responses, which are promising for the treatment of patients with advanced metastatic cancers.

An update in clinical utilization of photodynamic therapy for lung cancer

“…Therefore, the development of a novel combination of PDT and immune checkpoint blockade therapy could be beneficial for metastatic lung cancer 91 . Recently, Yang and colleagues developed a sequential PDT and photothermal using Gd-Ce6@SWNHs platform with cooperative and long-lasting antitumor immune responses for the treatment of patients with advanced metastatic cancer 92 . The application of novel PDT platforms, nanoparticle-based photosensitizers, and improved imaging and surveillance system is crucial to improve the efficacy of PDT in lung cancer treatment.…”

Injectable Adhesive Hydrogel as Photothermal‐Derived Antigen Reservoir for Enhanced Anti‐Tumor Immunity

“…In addition, NIR‐irradiated phototherapy has been reported to induce immunogenic cell death (ICD) and release damage‐associated molecular patterns, tumor‐associated antigens, and immunogenicity of cell debris, resulting in enhancing the immunogenic tumors in situ. [ 4b,36 ] Here, characteristic TDPAs induced by ICD including calreticulin (CRT) exposed on the surface of 4T1 cells and high‐mobility group box 1 protein (HMGB1) released from 4T1 cells after various treatments were investigated. As shown in Figure 2e,f, the highest level of CRT exposure and the most release of HMGB1 from 4T1 cells appeared in the groups of MnO 2 @PNI+NIR and MnO 2 @PND+NIR with similar amount.…”

Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation

“…The time point of 72 h following MH therapy was selected to capture early changes in both tumor infiltrating lymphocyte (TIL) populations and T cells in draining LNs, without allowing time for a systemic immune response, thus negating the possibility of an abscopal immune response in the contralateral tumor, [ 70 ] as has been observed in other studies. [ 71 ] Resulting tumor and LN cell samples were stained and characterized using flow cytometry to isolate and compare the populations of CD8+ and CD4+ T cells present.…”