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Additional file 1: Methods. 1.1 In vitro DSF release of DSF@HMONs; 1.2 In vitro photothermal effect of CuS; 1.3 In vitro cytotoxicity assay of HMONs. Figure S1. The releasing profiles of DSF from DSF@HMONs in aqueous solutions. Figure S2. In vitro photothermal-conversion assessment of CuS. Figure S3. Relative cell viability of 4T1 cancer cells after incubation with different concentrations (0, 6.25, 12.5, 25, 50, 100, and 200 ��g/mL) of HMONs for 24 and 48 h. Figure S4. Blood routine examination and serum biochemical levels of mice treated with 0 mg/kg, 5 mg/kg, 10 mg/kg, and 20 mg/kg of DSF@HCu. Figure S5. Histopathological examinations of major organs (heart, liver, spleen, lung, and kidney) from mice after different treatments.

Cordyceps militaris is a highly valued edible and medicinal fungus due to its production of various metabolites, including adenosine, cordycepin, N6-(2-hydroxyethyl)-adenosine, and carotenoids. The contents of these metabolites are indicative of the quality of commercially available fruit body of this fungus. In this work, the effects of environmental abiotic factors, including heat and light stresses, on the fruit body growth and metabolite production in C. militaris were evaluated during the late growth stage. The optimal growth temperature of C. militaris was 20 °C. It was found that a heat stress of 25 °C for 5–20 days during the late growth stage significantly promoted cordycepin and carotenoid production without affecting the biological efficiency. Light stress at 6000 lx for 5–20 days during the late growth stage significantly promoted cordycepin production but decreased the carotenoid content. Both heat and light stresses promoted N6-(2-hydroxyethyl)-adenosine production. In addition, gene expression analysis showed that there were simultaneous increases in the expression of genes encoding a metal-dependent phosphohydrolase (CCM_04437) and ATP phosphoribosyltransferase (CCM_04438) that are involved in the cordycepin biosynthesis pathway, which was consistent with the accumulation of cordycepin during heat stress for 5–20 days. A positive weak correlation between the cordycepin and adenosine contents was observed with a Pearson correlation coefficient of 0.338 (P