Lamellar Metal Oxide Based Nanoagent Realizing Intensive Interlamellar Ca²⁺ Release and Hypoxia Relief for Enhanced Synergistic Therapy

Abstract

As an emerging cancer treatment, Ca2+-loaded nanoagents can disorder intracellular calcium homeostasis to induce cancer cell death. However, the developed Ca2+ nanocarriers are very limited in variety. Herein, we developed a metal oxide based nanoagent, Ca0.35CoO2@ss-SiO2-Ce6 (denoted as CCO@ss-SiO2-Ce6), which not only intensively released Ca2+ but also realized enhanced photothermal and photodynamic therapy. The excellent photothermal conversion efficacy (48.01% at 808 nm laser illumination, 1 W/cm2), high heat-enhanced release rate of Ca2+ (50.09% at pH 4.5), and catalase-mimic activity to generate oxygen as well as the facilitated production of the singlet oxygen all contributed to the enhanced synergistic cancer therapy efficacy. The in vitro and in vivo experiments displayed that CCO@ss-SiO2-Ce6 demonstrated superior biocompatibility and remarkable suppressive tumor growth. This work opens a pathway for fabricating synergistic therapeutic nanoplatforms.

Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy

“…Aside from the direct use of Ca 2+ -based nanomaterials to induce Ca 2+ overload, certain nanomaterials can load Ca 2+ and disrupt intracellular Ca 2+ homeostasis to trigger cancer cell death. Especially, the unique layered structure of [77] Copyright 2021, American Chemical Society.…”

“…developed a nanoagent with a layered structure that linked chlorin e6 (Ce6) photosensitizer (CCO@ss‐SiO 2 ‐Ce6) to release Ca 2+ between layers to induce Ca 2+ overload and enhance PTT and PDT therapies under 808 and 660 nm laser irradiation (Figure 9A,B). [ 77 ] Elevated temperatures also promoted the release of Ca 2+ . Moreover, CCO@ss‐SiO 2 ‐Ce6 could catalyze the decomposition of intracellular H 2 O 2 into O 2 to alleviate hypoxia, promoting the production of singlet oxygen via Ce6 photosensitizer under 660 nm laser irradiation (Figure 9C).…”