Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 29, Pages 33712-33725Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c07592
Keywords
AuNCs; EGCG; MSOT; mild photothermal therapy; apoptosis; necroptosis
Funding
- National Natural Science Foundation of China [32071376]
- Research Grants Council, HKSAR Government [C5012-15E]
- Shenzhen Basic Research Funding Scheme [JCYJ20170818103614207]
- Science and Technology Innovation Commission of Shenzhen Municipality, China
- Research Grant Council, Hong Kong SAR Government [210220]
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A novel multifunctional nanotheranostic agent PAuE has been developed for multispectral optoacoustic tomography-guided photo-thermal therapy and chemotherapy, showing remarkable tumor growth inhibition in mouse models and providing a new insight into anti-cancer therapy.
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 photo-thermal 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-1 alpha) 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-1 alpha expression in a tumor environment provides a new insight into anti-cancer therapy.
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