A multichannel nucleic acid-based Ca2+ nanomodulator induces multilevel destruction of mitochondria for cancer therapy

Mitochondria play a crucial function in tumor proliferation and apoptosis, and inducing mitochondrial dysfunction in cells has emerged as a promising therapeutic approach for tumors. Here, curcumin (CUR) is enrolled in amorphous calcium phosphate (ACP) through the coprecipitation method, followed by Cy5.5-labeled DNA was adsorbed on its surface to propose an acidity-responsive nucleic acid-based nanomodulator (ACP@C-D) to enhance Ca²⁺ overload and mitochondrial biomineralization for cancer therapy by amplifying intra-mitochondrial Ca²⁺ concentration. After tumor cell administration, the ACP@C-D will disintegrate in the acidic environment to enhance Ca²⁺ overload by the combined interaction of a dramatic increase in Ca²⁺ concentration and Ca²⁺ efflux inhibition by Cur. Moreover, the mitochondrial targeting ability of Cy5.5 allows DNA enrichment at mitochondrial, and the phosphate on DNA provides reaction sites for Ca²⁺ to achieve mitochondrial biomineralization thus mitochondrial dysfunction, which is reported for the first time. The facile and functional strategy of the nanomodulator will provide new insights into inmitochondria-based cancer therapy.