1. Academic Validation
  2. MSOT-Guided Nanotheranostics for Synergistic Mild Photothermal Therapy and Chemotherapy to Boost Necroptosis/Apoptosis

MSOT-Guided Nanotheranostics for Synergistic Mild Photothermal Therapy and Chemotherapy to Boost Necroptosis/Apoptosis

  • ACS Appl Mater Interfaces. 2022 Jul 13. doi: 10.1021/acsami.2c07592.
Shiying Li 1 2 Kwok-Ho Lui 1 Wing-Sum Lau 3 Juyu Chen 3 Wai-Sum Lo 1 Xin Li 1 Yan-Juan Gu 1 Liang-Ting Lin 3 Wing-Tak Wong 1 4
Affiliations

Affiliations

  • 1 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 000000, China.
  • 2 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 3 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 000000, China.
  • 4 The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.
Abstract

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance Apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between Necroptosis and Apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering Necroptosis/Apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

Keywords

AuNCs; EGCG; MSOT; apoptosis; mild photothermal therapy; necroptosis.

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