4.8 Article

Targeting Proinflammatory Molecules Using Multifunctional MnO Nanoparticles to Inhibit Breast Cancer Recurrence and Metastasis br

Journal

ACS NANO
Volume 16, Issue 12, Pages 20430-20444

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c06713

Keywords

proinflammatory molecules; Toll-like receptor; nanoparticles; therapy-induced inflammation; photothermal therapy; breast cancer; tumor recurrence and metastasis

Funding

  1. NIH [UG3/UH3TR002151, RO1AR073935]
  2. Basic and Applied Basic Research Foundation of Guangdong Province, China [2021A1515220001]
  3. Australian Research Council [DE180100736]
  4. National Natural Science Foundation of China [82002776]
  5. Medical Scientific Research Foundation of Guangdong Province, China [B2019094]
  6. Australian Research Council [DE180100736] Funding Source: Australian Research Council

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Photothermal therapy is an effective treatment for tumors, but it can induce inflammatory responses and have undesirable side effects. This study developed multifunctional nanoparticles that can scavenge proinflammatory molecules and alleviate the inflammatory response caused by photothermal therapy. The nanoparticles also inhibit tumor recurrence and metastasis.
Photothermal therapy (PTT) is an effective treat-ment modality that is highly selective for tumor suppression and is a hopeful alternative to traditional cancer therapy. However, PTT-induced inflammatory responses may result in undesirable side effects including increased risks of tumor recurrence and metastasis. Here we developed multifunctional MnO nano-particles as scavengers of proinflammatory molecules to alleviate the PTT-induced inflammatory response. The MnO nanoparticles improve the PTT therapy by (1) binding and scavenging proinflammatory molecules to inhibit the proinflammatory molecule-induced Toll-like receptors (TLR) activation and nuclear factor kappa B (NF-kappa B) signaling; (2) inhibiting activated macrophage-induced macrophage recruitment; and (3) inhibiting tumor cell migration and invasion. In vivo experimental results showed that further treatment with MnO nanoparticles after laser therapy not only inhibited the PTT-induced inflammatory response and primary tumor recurrence but also significantly reduced tumor metastasis due to the scavenging activity. These findings suggest that MnO nanoparticles hold the potential for mitigating the therapy-induced severe inflammatory response and inhibiting tumor recurrence and metastasis.

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