Congener‐Induced Sulfur‐Related Metabolism Interference Therapy Promoted by Photothermal Sensitization for Combating Bacteria

Abstract

of biosynthesis, energy conversion, life activities, and stress resistance. [1] As prokaryotes facing environment independently, pathogen bacteria exhibit stronger metabolic homeostasis and thus achieve stronger stress resistance than human cells, allowing them causing persistent harm to human hosts. [2,3] In implantassociated infection (IAI) conditions, the intervention of biofilm, known as bacteria communities, enables bacteria to achieve better metabolic homeostasis and stronger antimicrobial resistance, becoming a common clinical dilemma. [4,5] Therefore, effectively destroying bacterial metabolic homeostasis is of great significance to bacteria killing, especially in IAI. The current antibiotics are mainly aiming at breaking the function of a specific target, such as cell membranes, cell walls, ribosomes, and transcription processes, which is more likely to cause bacterial resistance endangering public health. [6] However, few studies have been enabled to focus on the disruption of bacteria metabolic homeostasis in biochemical metabolic processes.Biochemical properties of essential elements, such as nitrogen (N), phosphorus (P), S, Se, and calcium (Ca), play important roles in intracellular biochemical reactions, and thus tightly connect with the regulation of cell metabolic state. [7] Interestingly, some congeners in the periodic table, S and Se, as well as Ca and strontium (Sr), have similar biochemical properties and share similar metabolic functions. [8] Among them, S and Se, two vital trace elements, exhibit intense and extensive reaction competition in cell metabolism, owning to their extremely similar biochemical properties as congeners. [9] Moreover, we found a definite biological diversity that bacterial cells can utilize inorganic S and Se, while human cells cannot. [10,11] H 2 S is the key metabolic intermediate in the pathway of inorganic S transformation and utilization in bacteria. [9] Meanwhile, H 2 Se shares all the same catalyzing enzymes and forms the homologous substituents with H 2 S in this pathway. [9,11,12] This mechanism makes it possible to allow intracellular overloaded H 2 Se for intervening with entire downstream sulfur-related metabolism state with cascade amplification and further destruction of bacteria metabolism Metabolic homeostasis is vital for individual cells to keep alive. Stronger metabolic homeostasis allows bacteria to survive in vivo and do persistent harm to hosts, which is especially typical in implant-associated infection (IAI) with biofilm intervention. Herein, based on the competitive role of selenium (Se) and sulfur (S) in bacteria metabolism as congeners, a congener-induced sulfur-related metabolism interference therapy (SMIT) eradicating IAI is proposed by specific destruction of bacteria metabolic homeostasis. The original nanodrug manganese diselenide (MnSe 2 ) is devised to generate permeable H 2 Se in bacteria, triggered by the acidic microenvironment. H 2 Se, the congener substitution of H 2 S, as a bacteria-specific intermediate metabolite, can embe...

Recent advances in hydrogels for preventing tumor recurrence

“…171 Recently, it has been confirmed that hydrogels in combination with PTT have gradually served as a strategy for averting bacterial infection. 172 Wu et al imbedded 125 I-labeled RGDY peptide-modified gold nanorods into a polyethylene glycol acrylate alginate DN hydrogel, which can obliterate pathogenic bacteria to overcome wound infection and keep cancer from recurring with the synergistic interaction of brachytherapy and PTT (Fig. 5B).…”

Biofilm Homeostasis Interference Therapy via 1O2‐Sensitized Hyperthermia and Immune Microenvironment Re‐Rousing for Biofilm‐Associated Infections Elimination

“…[22][23][24][25][26][27][28] Typically, bacteria can stand higher temperature than cells, and thus killing bacteria with PTT brings greater damage to surrounding tissues. [29] However, low-temperature PTT is insufficient to destroy rigid biofilms due to biofilm stress response (BSR). Instead, the elevated sublethal heat induces the accumulation of heat-shock proteins (HSPs) such as groEL, which prevents misfolding and aggregation of proteins.…”

Photothermal Nanozyme‐Based Microneedle Patch against Refractory Bacterial Biofilm Infection via Iron‐Actuated Janus Ion Therapy

“…[ 10 ] Our previous work demonstrated that heat stress could disrupt the stable structure of biofilms and activate bacterial metabolic processes, promoting intracellular iron overload against biofilms, which builds a basis for current ion therapy. [ 11 ] Nonetheless, BBIs with their higher thermotolerance capability would consequently limit the heat‐stress‐induced ion metabolism interference. [ 12 ] Therefore, promoting the thermal sensitization of biofilm by disrupting the heat shock response (HSR) is essential for enhancing the effectiveness of the ion therapy and combatting refractory BBI.…”

“…[10] Our previous work demonstrated that heat stress could disrupt the stable structure of biofilms and activate bacte rial metabolic processes, promoting intracellular iron overload against biofilms, which builds a basis for current ion therapy. [11] Owing to high antibiotic resistance and thermotolerance, bacterial biofilm infections (BBIs) are refractory to elimination. Iron is essential for bacterial growth and metabolism, and bacteria can thus accumulate iron from surrounding cells to maintain biofilm formation and survival.…”