Targeting regulated cell death in tumor nanomedicines

Abstract

Nanomedicines hold great potential in anticancer therapy by modulating the biodistribution of nanomaterials and initiating targeted oxidative stress damage, but they are also limited by the inherent self-protection mechanism and the evolutionary treatment resistance of cancer cells. New emerging explorations of regulated cell death (RCD), including processes related to autophagy, ferroptosis, pyroptosis, and necroptosis, substantially contribute to the augmented therapeutic efficiency of tumors by increasing the sensitivity of cancer cells to apoptosis. Herein, paradigmatic studies of RCD-mediated synergistic tumor nanotherapeutics are introduced, such as regulating autophagy-enhanced photodynamic therapy (PDT), targeting ferroptosis-sensitized sonodynamic therapy (SDT), inducing necroptosis-augmented photothermal therapy (PTT), and initiating pyroptosis-collaborative chemodynamic therapy (CDT), and the coordination mechanisms are discussed in detail. Multiangle analyses addressing the present challenges and upcoming prospects of RCD-based nanomedicines have also been highlighted and prospected for their further strengthening and the broadening of their application scope. It is believed that up-and-coming coadjutant therapeutic methodologies based on RCDs will considerably impact precision nanomedicine for cancer.

CeO2-Zn Nanocomposite Induced Superoxide, Autophagy and a Non-Apoptotic Mode of Cell Death in Human Umbilical-Vein-Derived Endothelial (HUVE) Cells

“…This cell death, as a result of autophagic failure, closely resembles a caspase-independent necrosis-like cell death associated with the accumulation of autophagosomes in cells [ 62 ]. Non-apoptosis mode of cell death caters a diverse mechanism of cell death that not only includes necrosis but also refers to cell death occurring due to autophagic failure, ferroptosis, programmed form of necrosis known as necroptosis, pyroptosis, mitotic catastrophe, oncosis and so on [ 64 ].…”

Nanoparticles-based phototherapy systems for cancer treatment: Current status and clinical potential

“…The analysis of the differences in the gene expressions before and after irradiation of melanoma cells have identified mainly changes in the genes associated with the immune response, further supporting the case of a milder treatment [ 30 ]. However, the thermal cell death promoted by PTT can also induce autophagy in the cancer cells, which require combination of PTT with anti-autophagy treatments to increase the efficacy of the therapy [ 31 ]. Combination therapies can also be useful to induce ferroptosis and to further increase the fraction of cells undergoing necroptosis [ 31 ] .…”

“…However, the thermal cell death promoted by PTT can also induce autophagy in the cancer cells, which require combination of PTT with anti-autophagy treatments to increase the efficacy of the therapy [ 31 ]. Combination therapies can also be useful to induce ferroptosis and to further increase the fraction of cells undergoing necroptosis [ 31 ] . Based on the principles of the cancer PTT, the ideal PTT agents should have following characteristics: strong light absorption capacity, excellent and stable light-to-heat conversion efficiency and brilliant biosafety and biocompatibility.…”

Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer

“…Cell death is a life phenomenon and an irreversible life process of cells. Cell death plays an indispensable role in the biological process of maintaining the normative homeostasis of the body and inhibiting the rapid proliferation of tumor cells ( 14 , 15 ). Cell death includes regulated cell death (RCD) and accidental cell death (ACD) ( 16 – 18 ).…”