Because toxic heavy metals tend to bioaccumulate, they represent a substantial human health hazard. Various methods are used to identify and quantify toxic metals in biological tissues and environment fluids, but a simple, rapid, and inexpensive system has yet to be developed. To reduce the necessity for instrument-dependent analysis, we developed a single, pH-dependent, nanosphere (NS) sensor for naked-eye detection and removal of toxic metal ions from drinking water and physiological systems (i.e., blood). The design platform for the optical NS sensor is composed of double mesoporous core–shell silica NSs fabricated by one-pot, template-guided synthesis with anionic surfactant. The dense shell-by-shell NS construction generated a unique hierarchical NS sensor with a hollow cage interior to enable accessibility for continuous monitoring of several different toxic metal ions and efficient multi-ion sensing and removal capabilities with respect to reversibility, longevity, selectivity, and signal stability. Here, we examined the application of the NS sensor for the removal of toxic metals (e.g., lead ions from a physiological system, such as human blood). The findings show that this sensor design has potential for the rapid screening of blood lead levels so that the effects of lead toxicity can be avoided.