State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Acta Biomater. 2021 Jul 1;128:435-446. doi: 10.1016/j.actbio.2021.04.006. Epub 2021 Apr 20.
Multi-modal combination therapy has attracted great attention, owing to the unsatisfactory therapeutic efficacy of conventional chemotherapy. Mesoporous silica-coated gold nanorods possess great potential in photothermal therapy and drug delivery. In this work, we fabricate a dual-responsive nanohybrid for combination treatment of the malignant tumor. In this system, gold nanorods are coated with the degradable mesoporous silica, and the chemotherapy drug doxorubicin (DOX) and photosensitizer (IR820) are co-loaded inside the pores of the silica. The encapsulation of hyaluronic acid (HA) endow the nanohybrids with mammary carcinoma targeting ability and better biocompatibility, owning to CD44+ receptor overexpressed in some cancer cells. As-prepared nanohybrids exhibit high responsiveness to a high glutathione (GSH) level and degrade rapidly in the presence of hyaluronidase (HAase) and GSH after endocytosis by 4T1 cells, allowing the efficient release of loaded DOX and IR 820 in tumor sites. Interestingly, near-infrared (NIR) laser not only triggers the generation of reactive oxygen species, but also remarkable photothermal efficacy originating from GNRs. Therefore, upon the irradiation of 808 nm NIR light, the combinatorial photodynamic, photothermal and chemotherapy is achieved, accordingly leading to a highly efficient antitumor outcome in vitro and in vivo. This strategy provides an ideal approach to constructing multimodal cancer therapy system. STATEMENT OF SIGNIFICANCE: • Dual-responsive nanohybrids for combinatorial therapy of breast cancer. • The nanohybrids exhibit both HAase and GSH stimuli-responsive behavior. • The nanohybrids exhibit light-activated PDT/PTT/chemotherapy. • The nanohybrids show good biosafety for potential clinical application.
多模态联合治疗因其常规化疗疗效不理想而受到广泛关注。介孔硅包覆金纳米棒在光热治疗和药物输送方面具有很大的潜力。在这项工作中，我们制备了一种用于恶性肿瘤联合治疗的双响应纳米杂化材料。在该体系中，金纳米棒被具有降解性的介孔硅所包覆，阿霉素（DOX）和光敏剂（IR820）共负载于硅孔内。透明质酸（HA）的包封使纳米杂化物具有乳腺癌靶向能力和更好的生物相容性，因为一些癌细胞中过度表达了 CD44+受体。所制备的纳米杂化物对高谷胱甘肽（GSH）水平具有高响应性，并且在 4T1 细胞内摄取后，在透明质酸酶（HAase）和 GSH 的存在下迅速降解，允许在肿瘤部位有效释放负载的 DOX 和 IR820。有趣的是，近红外（NIR）激光不仅触发活性氧的产生，而且还源自 GNRs 的显著光热效应。因此，在 808nm NIR 光的照射下，实现了组合光动力、光热和化学疗法，从而在体外和体内均实现了高效的抗肿瘤效果。该策略为构建多模态癌症治疗系统提供了一种理想的方法。
