Breast cancer is the most common one in women worldwide and doxorubicin (Dox) is one of the most commonly used and effective drugs for breast cancer treatment.Unfortunately,Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency.It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment,in this work,a multifunctional calcium phosphate nanoformulation (ICG-Dox/DNA@CaP) was developed by co-loading Dox/DNA complexes and indocyanine green (ICG) molecules for photothermal therapy (PTT)-enhanced chemotherapy.In this nanocomposite,using DNA as Dox carrier facilitated Dox loading into the CaP matrix,and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium (pH 7.4).In specific,ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment,such as tumor microenvironment and endosome/lysosome.Moreover,Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite.This work has demonstrated a new strategy to combine FDA-approved therapeutics (Dox and ICG) in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect,and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.