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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.

Uniting combinational strategies has been confirmed to be a robust choice for high-performance cancer treatment due to their abilities to overcome tumor heterogeneity and complexity. However, the development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. In this study, we integrated multicomponent hyaluronic acid (HA), protamine (PS), nanodiamonds (NDs), curcumin (Cur), and IR780 into a single nanoplatform (denoted as HPNDIC) based on the combination of hydrophobic and electrostatic noncovalent interactions for dual-modal fluorescence/photoacoustic imaging guided ternary collaborative Cur/photothermal/photodynamic combination therapy of triple-negative breast cancer (TNBC). A two-step coordination assembly strategy was utilized to realize this purpose. In the first step, PS was utilized to modify the NDs clusters to form positively charged PS@NDs (PND) and the simultaneous encapsulation of the natural small-molecule drug Cur and the photosensitive small-molecule IR780 (PNDIC). Second, HA was adsorbed onto the outer surface of the PNDIC through charge complexation for endowing a tumor-targeting ability (HPNDIC). The resulting HPNDIC had a uniform size, high drug-loading ability, and excellent colloidal stability. It was found that under the near-infrared irradiation condition, IR780 could be triggered to exhibit both PTT/PDT dual-pattern therapy effects, leading to an enhanced therapy efficiency of Cur both in vitro and in vivo with good biocompatibility. Due to the intrinsic imaging property of IR780, the biodistribution and accumulation behavior of HPNDIC in vivo could be monitored by dual-modal fluorescence/photoacoustic imaging. Taken together, our current work demonstrated the assembly of a NDs-based multicomponent theranostic platform for dual-modal fluorescence/photoacoustic imaging guided triple-collaborative Cur/photothermal/photodynamic against TNBC.

We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ΔNp63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy.