Oncocyte Membrane-Camouflaged Multi-Stimuli-Responsive Nanohybrids for Synergistic Amplification of Tumor Oxidative Stresses and Photothermal Enhanced Cancer Therapy

Abstract

The combination of various therapeutic modalities has received considerable attention for improving antitumor performance. Herein, an innovative nanohybrid, namely CaO 2 @FePt-DOX@PDA@CM (CFDPM), was developed for synergistic chemotherapy/chemodynamic therapy/Ca 2+ overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy. Camouflage of the 4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue. Ca 2+ , released from CaO 2 , could lead to mitochondrial dysfunction and facilitate the production of reactive oxygen species to amplify intracellular oxidative stress. Meanwhile, the increase of H 2 O 2 concentration could enhance the efficiency of the chemodynamic therapy (CDT). Moreover, the hypoxic condition could be alleviated remarkably, which is attributed to the sufficient O 2 supply by CaO 2 , resulting in the suppression of drug resistance and promotion of the chemotherapeutic effect. The nanohybrids involving Ca 2+ overloading/CDT/chemotherapy could synergistically amplify the tumor oxidative stresses and remarkably aggravate the death of cancer cells. Significantly, the excellent photothermal conversion performance of CFDPM could further promote the tumoricidal effect. The in vitro and in vivo studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue, which would open a valuable avenue for effective cancer treatment.

Composite Nanoplatforms Based on Nanocalcium Peroxide for Cancer Treatment: From Monotherapy to Combination Therapy

“…[66] Although CaO 2 does not play a direct role in promoting PTT treatment, it can indirectly alleviate the hypoxic microenvironment of tumors, and the Ca 2+ generated can amplify the oxidative stress of tumor cells. Hence, CaO 2 serves mainly as a drug carrier material in PTT, offering [67] Copyright 2022, American Chemical Society.…”

“…Figure 8. a) The preparation path of CFDPM NPs; b) the therapeutic principles of synergistic therapy in tumor cells; c) the fluorescent images of living cells; d) the fluorescence intensity analysis of major organs and tumor cells and tissues after treatment for 12 h; e) the tumor tissue cells are stained with different staining agents; f) the photothermal images. Reproduced with permission [67]. Copyright 2022, American Chemical Society.…”

Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy

“…Besides, CaO 2 could also be utilized as a drug carrier for loading drugs that destroy cellular Ca 2+ buffering capacity, promote Ca 2+ influx, or inhibit Ca 2+ efflux, thereby enhancing the Ca 2+ overload efficiency. [56,57] For instance, it was found that the Transient Receptor Vanilloid 1 (TRPV1) thermosensitive cation channel could promote Ca 2+ influx when the temperature exceeds 43 • C. Based on this finding, Zhou and colleagues designed a near-infrared (NIR)-responsive DPPC-DSPE-PEG2000-NH 2 @PDPP@CaO 2 @doxorubicin NPs to acquire chemotherapy, Ca 2+ overload and PTT. [58] With NIR irradiation, the PTT effect could elevate the local temperature at the tumour site, activating the TRPV1 channel and promoting Ca 2+ influx to achieve more efficient Ca 2+ overload therapy.…”

Recent Advances in Calcium‐Based Anticancer Nanomaterials Exploiting Calcium Overload to Trigger Cell Apoptosis

“…The combined FePt could convert H 2 O 2 produced by CaO 2 into HO•, leading to enhanced apoptosis. [85] In another work, CaO 2 nanomaterials modified by Fe 3+ /TA (tannic acid) polyphenol network were prepared to treat cancer by Ca 2+ overload and CDT. [86,87] Notably, HO• generated via the Fenton reaction desensitized the intracellular calcium ion proteins, promoting the occurrence of calcium overload and accelerating the death of cancer cells.…”