Coordinating the Mechanisms of Action of Ferroptosis and the Photothermal Effect for Cancer Theranostics

Abstract

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron‐chelating agent with BSA, thus leading to biocompatible and stable Cro‐Fe@BSA nanoparticles (NPs). The Cro‐Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature‐dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat‐induced formation of heat shock proteins and thus the self‐protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro‐Fe@BSA NPs also enabled safe and reliable cancer theranostics.

Simultaneous Monitoring of the Adenosine Triphosphate Levels in the Cytoplasm and Nucleus of a Single Cell with a Single Nanowire-Based Fluorescent Biosensor

“…A similar phenomenon was also observed in the oligomycin-treated HeLa cells (Figure S20). The response of the nucleus and cytoplasm to oligomycin may be related to the “self-protection” of the cell itself . It is known that the replication and transcription of DNA occurred in the nucleus and is associated with cell multiplication.…”

Copper nanocrystalline-doped folic acid-based super carbon dots for an enhanced antitumor effect in response to tumor microenvironment stimuli

“…After 14 days, the tumors, hearts, livers, spleens, lungs, and kidneys were executed and removed. Tumor volumes were calculated according to eqn (5), where L, W and V are the length, width and volume of the tumor, respectively.…”

“…Traditional treatments such as chemotherapy, surgery and radiation therapy suffer from large trauma, high toxicity and side effects and drug resistances, compelling human beings to search for new treatments constantly. Photodynamic therapy (PDT), [1][2][3] photothermal therapy (PTT) 4,5 and chemodynamic therapy (CDT) 6,7 have been the newly developed methods for cancer therapy in recent years. Both PDT and PTT are light-responsive therapies, with the former producing singlet oxygen to kill cancer cells and the latter using the high temperature generated by the photothermal effect to kill cancer cells.…”

Crystal engineering of ferrocene-based charge-transfer complexes for NIR-II photothermal therapy and ferroptosis

“…Among them, ferroptosis, a new type of iron-dependent programmed cell death featured as the peroxidation of unsaturated fatty acid on the cell membrane, is an ideal candidate for the combination with PTT. On the one hand, ferroptosis can suppress the expression of heat shock proteins (HSPs) to improve the PTT efficiency, on the other hand, PTT can promote the ferroptosis achieving a synergistic effect [17][18][19][20] . The main mechanism of ferroptosis is related to the imbalance of cellular redox homeostasis including cellular GSH depletion or ROS accumulation 21,22 .…”

“…On the one hand, ferroptosis can suppress the expression of heat shock proteins (HSPs) to improve the PTT efficiency, and on the other hand, PTT can promote ferroptosis achieving a synergistic effect. [17][18][19][20] The main mechanism of ferroptosis is related to the imbalance of cellular redox homeostasis including cellular GSH depletion or ROS accumulation. 21,22 Fortunately, our group has previously observed that the CTCs containing thiol-sensitive acceptors not only possessed absorption in the NIR-II region but also showed GSH depletion induced ferroptosis, which can enhance antitumor efficacy.…”