Bacterial infection is rising as a threatening health issue. Because of the present delay in early diagnosis of bacterial diseases as well as the abuse of antibiotics, it has become a vital issue in the development of in-time detection and therapy of bacterial infections. Herein, we designed a multifunctional nanotheranostics platform based on the unique micro-environment of bacterial infections to achieve specific bioimaging and simultaneous inactivation of the target bacteria. We showed that in bacterial infections, the metal precursors (i.e., HAuCl₄, FeCl₂, and herring sperm DNA) could be readily bio-self-assembled to multifunctional nanoclusters (NCs) that exhibit luminescence, in which AuCl₄^– was biosynthesized via reductive biomolecules such as NADPH to the fluorescent AuNCs. The DNA may assist as an encapsulation and delivery vector, and Fe²⁺ served as a fluorescence intensifier and reduced reactive oxygen species (ROS) to produce the iron oxides. While the bacteria were being visualized, the microenvironment-responsive NCs were enabled to sterilize bacteria efficiently due to electrostatic effect, cell membrane destruction, inhibition of biofilm formation, and ROS accumulation. Besides, the bio-responsive self-assembled NCs complexes contributed to accelerating bacteria-infected wound healing and showed negligible side effects in long-term toxicity tests in vivo. Also, intracellular molecules involved in microenvironmental response were investigated. The work may become an effective strategy for the detection and real-time sterilization of intractable bacterial infections.

Proteins are excellent templates and stabilizers for Au nanoclusters (NCs) because of their abundant thiol groups and unique internal environments. However, high-molecular weight (MW) proteins with special quaternary structures are rarely reported as such templates. Considering that proteins may afford different spatial configurations as templates for Au NCs, we focused on alkaline phosphatase, catalase, and fibrinogen (MW range from 150 to 340 kDa) as direct templates for synthesizing Au NCs. We demonstrated that both Cu²⁺ and Hg²⁺ could induce photoluminescence (PL) quenching of these Au NCs, while their binding mechanisms were different. Therefore, significant PL recovery by amino acids, e.g., histidine and cysteine, was observed for Cu²⁺-treated Au NCs, but not Hg²⁺-treated Au NCs, allowing for selective detection of Hg²⁺ by using histidine as a masking agent. The detection ranges were 0.06–2.0 μM for Hg²⁺ and 0.04–5.0 μM for Cu²⁺, with low limits of detection of 0.02 and 0.01 μM, respectively. The PL change showed opposite tendency for histidine and cysteine at higher concentrations, resulting in different PL outputs. Using dual metal ion and dual amino acid combinations, an integrated PL logic gate was fabricated. This work improves the understanding of the PL mechanisms of complicated protein-localized Au NCs.

Early diagnosis remains highly important for efficient cancer treatment, and hence, there is significant interest in the development of effective imaging strategies. This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe²⁺ and Zn²⁺ ions into cancer cells (i.e., HeLa, U87, and HepG2 cancer cells). We found that the biocompatible metal ions Fe²⁺ and Zn²⁺ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe₃O₄ nanoclusters. These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging. Meanwhile, for normal cells (i.e., L02) and tissues, neither fluorescence nor any other obvious difference could be detected between pre- and post-injection. This multimodal bioimaging strategy based on the in situ biosynthesized Zn & Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.

Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin (TSPP) and TiO₂ nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO₂ nanocomposites can significantly (p < 0.01) lower the concentrations of serum biomarkers (tumor necrosis factor-α and interleukin-17) in a collagen induced arthritis (CIA) murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO₂ nanocomposites. Microarray data analysis illustrated that rno-mir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO₂ nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.

In this study, we have explored the possibility of the application of the functionalized silver nanoparticles (Ag NPs) as drug carriers allied with anticancer drug daunorubicin (DNR) for efficient cancer chemotherapy. The results demonstrate that Ag NPs can enhance the intracellular drug DNR accumulation concentration in the leukemia K562 cells and thereby increase the killing effect on the leukemia K562 cells.