Combined hyperthermia and photodynamic therapy (PDT) are effective in the treatment of primary breast cancer, but its performance in deeply metastatic sites remains unsatisfactory.

Checkpoint blockade immunotherapy, as a clinical modality against metastasis via activating tumor‐specific T cells, has exhibited unsatisfactory therapeutic efficacy in metastatic tumors due to the inefficient activation of immune responses.

Recently, DONG Wenfei’s group in Suzhou Institute of Biomedical Engineering and Technology of Chinese Academy of Sciences proposed a synergistic immunogenic cell death strategy based on the combination of PDT and magnetic hyperthermia to enhance the anti-metastatic efficacy of checkpoint blockade immunotherapy.

PDT and hyperthermia‐triggered immunogenic cell death, including releasing tumor‐associated antigens, danger‐associated molecular patterns and proinflammatory cytokines, which facilitate the redistribution and activation of immune effector cells with enhanced tumor‐specific T cell infiltration.

Herein, scientists developed Janus nanobullets integrating Ce6-loaded disulfide-bridged mesoporous organosilica bodies with magnetic heads (M-MONs@Ce6) for redox-/pH-triggered photosensitizer release in tumor microenvironments accompanying their matrix collapse, corresponding glutathione (GSH) depletion and reactive oxygen species (ROS) augmentation.

Then, cancer cell membrane cloaking enables favorable tumor-targeted accumulation and increased blood circulation time of M-MONs@Ce6.

Experimental results show that the combination of PDT and magnetic hyperthermia significantly limits tumor growth and simultaneously triggers a sequence of immunogenic cell death to synergistically induce a tumor-specific immune response.

Combined with a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody, this biomimetic and biodegradable nanoplatform mediates the notable suppression of light-irradiated primary tumors and deeply metastatic foci with low systematic toxicity, thus potentially advances the development of combined hyperthermia, PDT and immunotherapy to treat metastatic breast cancer.

This work entitled “Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti‐Metastatic Immunotherapy” has been published on the Advanced Science, and chosen for the back cover.

Figure 1. A schematic of the synthetic procedure for the cancer cell membrane-cloaked Ce6-loaded Janus magnetic mesoporous organosilica nanoparticles (CM@M-MON@Ce6) and their application for combined PDT and magnetic hyperthermia to further potentiate a CTLA-4 blockade to enhance synergistic antitumor immunity in treating metastatic BC. (Image by WANG Zheng)

Figure 2. Characterization of M-MON@Ce6. (a) TEM images of M-MONs. (b) M-MONs were immersed in 5 mM GSH solution for 1, 3, and 5 days. (c) The magnetization curve, (d) temperature-time curves, and (e) N2 sorption isotherms of M-MONs. (f) Drug release profiles of Ce6@M-MONs in 0 and 5 mM GSH (pH=7.4 and 5.5). (g) Time-dependent SOSG fluorescence in Ce6 and M-MON@Ce6 solutions. (h) Intracellular GSH levels of MCF-7 cells after treatment with M-MON@Ce6 for 12 h. The data are presented as the mean ± S.D. (n = 3). *P < 0.05 vs. the M-MON@Ce6 group. (Image by WANG Zheng)

Figure 3. Metastasis and immune responses after combined PDT and magnetic hyperthermia with CM@M-MON@Ce6. (a) Representative images of lung tissues with observable metastatic nodules. (b) The number of pulmonary metastatic nodules and (c) primary tumor weights of 4T1 tumor-bearing mice from each group over 21 days. After 5 days of combined PDT and magnetic hyperthermia, serum and primary tumor tissue were collected for the analysis of (d) HMGB1, (e) TNF-α, (f) IFN-？, and (g) IL-6 levels in serum and for the analysis of (h) the ratios of CD8+T cells/CD4+T cells, (h) CTL content, and (j) Treg content in the primary tumor tissues. The data are presented as the mean ± S.D. (n = 5, *p < 0.05). (Image by WANG Zheng)

Contact

XIAO Xintong

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences (http://www.sibet.cas.cn/)

Phone: 86-512-69588013

E-mail: xiaoxt@sibet.ac.cn