Hypothermal photothermal therapy (HPTT) employs hyperthermia (<45 °C) to destroy tumor cells with negligible side effects to the surrounding normal tissues. Despite extensive studies, the clinical translation of HPTT is severely hindered, owing to the discounted therapeutic effect and maximum permissible power of near-infrared (NIR) laser by food and drug administration (FDA). Herein, we report a rational design of red blood cell membranes (RBCs) coated FeS 2 (FeS 2 @RBCs) with strong absorption at NIR-Ⅱ window for effective HPTT augmented chemodynamic therapy (CDT). FeS 2 @RBCs exhibits prolonged blood circulation and negligible immune response, leading to improved tumor accumulation for enhanced HPTT. Furthermore, the CDT effect of FeS 2 @RBCs is significantly augmented by the temperature elevation in the tumor region, which leads to the synergetic HPTT and CDT. Lipidomics analysis reveals that the damage of tumor cells by CDT is via the lipid peroxidation. In addition, FeS 2 @RBCs exhibits self-enhanced magnetic resonance imaging after reacting with H 2 O 2 in tumor region for imaging-guided laser irradiation. Thus, FeS 2 @RBCs achieves remarkable inhibition of subcutaneous 4T1 breast tumor growth without obvious side effects by a 1064 nm laser irradiation of 1.0 W/cm 2 (FDA approved power density). Overall, this work provides a HPTT augmented CDT strategy for effective cancer therapy with a clinical approved laser power, which may pave the way for the clinical application of HPTT augmented CDT in the future.
Bo Zhang,Chen-wen Shao,Kang-Min Zhou,Qin Li,Yong-Tao Duan,Yu-Shun Yang,Hai-Liang Zhu
Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.
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