A multifunctional nanodiamond-based nanoplatform for the enhanced mild-temperature photothermal/chemo combination therapy of triple negative breast cancer via an autophagy regulation strategy. Issue 31 (28th July 2021)

• Record Type: Journal Article
• Authors: Cui, Xinyue; Liang, Zhaoyuan; Lu, Jianqing; Wang, Xuan; Jia, Fan; Hu, Qin; Xiao, Xiangqian; Deng, Xiongwei; Wu, Yan; Sheng, Wang
• Is Part Of: Nanoscale. Volume 13:Issue 31(2021)
• Page Start: 13375
• Page End: 13389
• Publication Date: 2021-07-28
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d1nr03161a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : A multifunctional nanodiamond-based theranostic nanoplatform was fabricated that exhibited enhanced mild-temperature photothermal/chemo combination therapy efficiency via an autophagy regulation strategy against triple negative breast cancer. Abstract : Owing to its aggressive biological behavior, the lack of specific targets, and the strong therapeutic resistance of triple negative breast cancer (TNBC), current therapeutic strategies are still limited. The combination of multiple treatments has been confirmed as a promising strategy for TNBC therapy. However, the efficacy of combination therapy can be restricted due to increasing therapeutic resistance to various treatments. Herein, we constructed a nanodiamond (ND)-based nanoplatform for augmented mild-temperature photothermal/chemo combination therapy against TNBC, weakening the therapeutic resistance via autophagy inhibition enabled by the NDs. A layer-by-layer self-assembly approach was utilized to construct the ND-based nanoplatform. First, the NDs were modified with protamine sulphate (PS). Meanwhile, the photosensitizer indocyanine green (ICG) and the HSP70 small molecule inhibitor apoptozole (APZ) could be synchronously incorporated to form positively charged PS@ND (ICG + APZ). Then negatively charged hyaluronic acid (HA) was assembled onto the outer face of PS@ND (ICG + APZ) to form the NPIAs. Finally, the positively charged small molecule anti-cancer drug doxorubicin (DOX) could be adsorbed onto the surface of the NPIAs through electrostatic interactions (NPIADs). The resulting NPIADs could be triggered by NIR laser irradiation to exhibit enhanced mild-temperature photothermal therapy (PTT) effects via suppressing the expression of HSP70, and PTT combined with chemotherapy could further enhance the anti-tumor efficacy. Subsequently, the sensitivity of MDA-MB-231 cells could be significantly improved through the weakening of the thermal/drug resistance via autophagy inhibition, leading to augmented combination therapy that is efficient both in vitro and in vivo . Furthermore, the NPIADs could be used as a theranostic nanoplatform for fluorescence (FL) and photoacoustic (PA) imaging. Taken together, this study demonstrated a multifunctional ND-based nanoplatform for FL/PA imaging-guided augmented mild-temperature photothermal/chemo combination therapy via an autophagy regulation strategy against TNBC.