"Cluster Bomb" Based Bismuth Nano-in-Micro Spheres Formed Dry Powder Inhalation for Thermo-Radio Sensitization Effects of Lung Metastatic Breast Cancer.

Lung metastatic breast cancer (LMBC) is mainly diagnosed through CT imaging and radiotherapy could be the most common method in the clinic to inhibit tumor proliferation. While the sensitivity of radiotherapy is always limited due to the hypoxic tumor microenvironment and high doses of irradiation easily induce systemic cytotoxicity. Metal-based materials applied as radiosensitizers have been widely investigated to improve efficiency and reduce the doses of irradiation. Herein, it is aimed to overcome these problems by designing biodegradable lipid-camouflaged bismuth-based nanoflowers (DP-BNFs) as both a photo-thermo-radiosensitizer to develop a novel photothermal therapy (PTT) and radiotherapy combination strategy for LMBC treatment. To achieve effective lung deposition, "Cluster Bomb" structure-based DP-BNFs nano-in-micro dry powder inhalation (DP-BNF@Lat-MPs) are formulated through spray-dried technology. The DP-BNFs "cluster" in the microsphere to improve their tumor-targeted lung deposition with a high fine particle fraction followed by burst releasing of DP-BNFs for targeting delivery and LMBC therapy. The DP-BNF@Lat-MPs exhibit excellent photothermal conversion efficiency, radiotherapy enhancement, and CT imaging ability in vitro, which synergistically inhibit cell proliferation and metastasis. In vitro and in vivo data prove that combining PTT and radiotherapy with DP-BNF@Lat-MPs as a thermo-radio dual-sensitizer significantly enhances LMBC tumor metastasis inhibition with good biocompatibility and low toxicity.

Lipid-coated bismuth nanoflower as the thermos-radio sensiti for therapy of lung metastatic breast cancer: Preparation, optimisation, and characterisation.

Lung metastatic breast cancer (LMBC) leads to a large number of deaths in women with breast cancer, and radiotherapy has been considered the common assay for tumour therapy except for surgery. However, radiotherapy still faces problems of low efficiency due to resistance and easily induced side effects. Here, the authors designed lipid-decorated bismuth-based nanoflowers (DP-BNFs) as both a radiosensitiser and a photothermal therapy agent for LMBC treatment. The BNFs were prepared by oxidation of bismuth nitrate and subsequent reduction using sodium borohydride. The preparation parameters and formulation of DP-BNFs were optimised via a single-factor experiment, with the factors including reaction temperature, a molar ratio of reducing agents, and the types and amount of decorated lipid materials. The result indicated that the BNFs prepared at 170°C with the Bi/NaBH4 ratio of 1:0.7 exhibited the best yield and particle size around 160 nm. After being spray dried with lactose to prepare dry powder inhalation (DP-BNF@Lat-MPs), their effects on improving therapeutic efficiency of the radiotherapy and photothermal therapy combination were measured using the western blot assay to determine the tumour apoptosis. In a word, DP-BNF@Lat-MPs could be a novel inhalable integrated microsphere that provides a new possibility for thermoradiotherapy of LMBC.