“Cluster Bomb” Based Bismuth Nano‐in‐Micro Spheres Formed Dry Powder Inhalation for Thermo‐Radio Sensitization Effects of Lung Metastatic Breast Cancer

Abstract

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.

A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review)

“…The results demonstrated a notable reduction in tumor volume in both the NIR and IR groups, with the combined treatment of radiotherapy and photothermal therapy exhibiting superior effects compared to monotherapy. Western blotting indicated that the synergistic effect of these treatments downregulated the expression of Snail and upregulated the expression of E-cadherin, effectively inhibiting tumor metastasis ( 90 ).…”

Implantable, 3D-Printed Alginate Scaffolds with Bismuth Sulfide Nanoparticles for the Treatment of Local Breast Cancer via Enhanced Radiotherapy

“…In particular, radiosensitizers in the form of metal nanoparticles with high atomic number ( Z ), which are deposited in tumor tissue and have a dose-increasing effect, are preferred as an alternative therapeutic route that can overcome the mentioned limitations and improve the therapeutic window . Some high- Z metal nanoparticles have been proposed for breast cancer treatment, such as gadolinium ( Z = 64), hafnium ( Z = 72), tantalum ( Z = 73), gold ( Z = 79), and bismuth ( Z = 83). − Bismuth (Bi), which has the highest Z among these elements and is biocompatible and stable in forms such as sulfur and oxide, has been shown to have a greater radiosensitization effect when the particle size, concentration, and area of influence of bismuth nanoparticles are the same compared to gold and platinum nanoparticles, and they have been used in the treatment of breast cancer to increase therapeutic efficacy as radiosensitizer nanoparticles. − …”

Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors

“…Metastasis is the result of the spread of tumor cells to foreign organs and stands as a primary contributor to the high lethality of cancer. [1][2][3][4] Lungs are one of the organs most susceptible to colonization by cancer cells, given their integral role in the circulatory metabolic system. 5,6 Lung cancer exhibits the highest mortality rate nationwide, and the majority (44%) of lung cancer patients are diagnosed with metastatic disease with a five-year relative survival rate of only 8%.…”