*2.1. Reagents and Materials*

Silk fibroin (SF) protein was purchased from Xi'an Shennong Biotechnology Co., Ltd. (Xi'an, China). The protein has been purified and used as it received. Cadmium nitrate (Cd(NO3)2) was purchased from Aladdin Reagent Co., Ltd. (Shanghai, China). Lead nitrate (Pb(NO3)2), nickel nitrate (Ni(NO3)2), copper sulphate (CuSO4), sodium chloride (NaCl), potassium chloride (KCl), potassium dihydrogen phosphate (KH2PO4), dibasic sodium phosphate (Na2HPO4), sodium hydroxide (NaOH), and nitric acid (HNO3) were obtained from Kelong Chemical Reagent Company (Chengdu, China). All the reagents were of analytical grade and used as received. Wahaha ® purified water (Wahaha, Hangzhou, China) was used for the preparation of solutions and throughout the experiments.

SF solution was prepared in water and the concentration was adjusted to the value as needed by experiments. Pb(NO3)2, Cd(NO3)2, and Ni(NO3)2 stock solutions of 1 × 10<sup>3</sup> mg L−<sup>1</sup> were prepared in water and working solutions were prepared freshly for daily use. The pH was adjusted by using small amounts of 0.1 mol L−<sup>1</sup> NaOH or 0.1 mol L−<sup>1</sup> HNO3 solutions without significantly altering the HMIs concentration. Solution pH was monitored using a pH meter (PHS-3C, Yidian Inc., Ltd., Shanghai, China).

### *2.2. Synthesis of SF@Cu-HNFs via Self-Assembly*

0.01 M phosphate bu ffer solution (PBS, pH = 7.4): Weigh 0.135 g of potassium dihydrogen phosphate, 0.71 g of disodium hydrogen phosphate, 4 g of sodium chloride, and 0.1 g of potassium chloride in order using an analytical balance, and add an appropriate amount purified water was stirred to dissolve it. The solution was transferred to a 500 mL volumetric flask, and the volume was adjusted with purified water. It was then transferred to a reagen<sup>t</sup> bottle and refrigerate at 4 ◦C until use.

By utilizing SF protein as natural biomaterial and Cu3(PO4)2 as inorganic component, the hybrid nanoflowers of SF@Cu-HNFs were synthesized according to similar methods developed for BSA-based and laccase-based nanoflowers described with some modification [31,56]. In brief, 4 mL of PBS (pH = 7.4) containing di fferent SF concentration was firstly added with 40 μL CuSO4 solution (100 mM). Then resultant mixtures were gently shaken for 5 min and followed by incubation at 25 ◦C with di fferent preparation time. Finally, blue hybrid nanoflowers were collected, washed, with deionized water several times and dried by vacuum freeze-drying.
