The diverse effects of cisplatin on tumor microenvironment: Insights and challenges for the delivery of cisplatin by nanoparticles

Cisplatin is a well-known platinum-based chemotherapy medication that is widely utilized for some malignancies. Despite the direct cytotoxic consequences of cisplatin on tumor cells, studies in the recent decade have revealed that cisplatin can also affect different cells and their secretions in the tumor microenvironment (TME). Cisplatin has complex impacts on the TME, which may contribute to its anti-tumor activity or drug resistance mechanisms. These regulatory effects of cisplatin play a paramount function in tumor growth, invasion, and metastasis. This paper aims to review the diverse impacts of cisplatin and nanoparticles loaded with cisplatin on cancer cells and also non-cancerous cells in TME. The impacts of cisplatin on immune cells, tumor stroma, cancer cells, and also hypoxia will be discussed in the current review. Furthermore, we emphasize the challenges and prospects of using cisplatin in combination with other adjuvants and therapeutic modalities that target TME. We also discuss the potential synergistic effects of cisplatin with immune checkpoint inhibitors (ICIs) and other agents with anticancer potentials such as polyphenols and photosensitizers. Furthermore, the potential of nanoparticles for targeting TME and better delivery of cisplatin into tumors will be discussed.