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This review summarizes state of the art synthesis and applications of carbon dots (CDs) with pH-responsive fluorescence. Following an introduction, the first section covers methods for the preparation of pH-responsive CDs, with subsections on general methods for preparing CDs (by hydrothermal, solvothermal, electrochemical, microwave, laser ablation, pyrolysis or chemical oxidation polymerization methods), and on precursors for synthesis. This is followed by a section on the mechanisms of pH-responsivity (by creating new functional groups, change of energy levels, protonation and deprotonation, aggregation, or by introduction shells). Several Tables are presented that give an overview of the wealth of methods and materials. A final section covers applications of carbon dots (CDs) with pH-responsive fluorescence for sensing, drug delivery, and imaging. The conclusion summarizes the current status, addresses challenges, and gives an outlook on potential future trends. Graphical abstract The synthesis and biological applications of carbon dots(CDs) with pH-responsive fluorescence are summarized. Precursors and methods for preparation of pH-responsive CDs, mechanisms of pH-responsivity, and biological applications of CDs with pH-responsive fluorescence for sensing, drug delivery, and imaging are discussed.

Infected burn wounds are characterized by persistent drug‐resistant bacterial infection coupled with an inflammatory response, impeding the wound‐healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF‐8 NPs) was prepared using curcumin (CCM), an aggregation‐induced emission luminogens (TTD), and ZIF‐8 for infection‐induced wound healing. The CCM+TTD@ZIF‐8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response‐guided photodynamic therapy (PDT), and anti‐inflammatory. The positive charges of ZIF‐8 NPs allowed the targeting of drug‐resistant bacteria in infected wounds, thereby realizing fluorescence imaging of bacteria by emitting red fluorescence at the infected site upon blue light irradiation. The pH‐responsive characteristics of the CCM+TTD@ZIF‐8 NPs also enabled controllable CCM release onto the infected wound site, thereby promoting the specific accumulation of ROS at the infected site, with outstanding bactericidal efficacy against drug‐resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) strains in vitro/in vivo. Additionally, due to the excellent bactericidal effect and anti‐inflammatory properties of CCM+TTD@ZIF‐8 NPs combined with blue light irradiation, the regeneration of epidermal tissue, angiogenesis, and collagen deposition was achieved, accelerating the healing process of infected burn wounds. Therefore, this CCM+TTD@ZIF‐8 NPs with multifunctional properties provides great potential for infected burn wound healing. An intelligent acid responsive ZIF‐8 nanoparticle (CCM + TTD@ZIF‐8 NPs) is proposed and is used to promote the healing of burns and infected wounds. It can effectively target bacteria and achieve bacterial imaging under blue light irradiation, effectively releasing CCM and TTD in acidic environments, thereby inhibiting the inflammatory microenvironment and promoting wound healing.

Despite its widespread usage as a chemotherapy drug in cancer treatment, doxorubicin (DOX) has limitations such as short in vivo circulation time, low solubility, and poor permeability. In this regard, a pH‐responsive chitosan (CS)‐ montmorillonite (MMT)‐ nitrogen‐doped carbon quantum dots (NCQDs) nanocomposite was first developed, loaded with DOX, and then incorporated into a double emulsion to further develop the sustained release. The incorporated NCQDs into the CS‐MMT hydrogel exhibited enhanced loading and entrapment efficiencies. The presence of NCQDs nanoparticles in the CS‐MMT hydrogel also resulted in an extended pH‐responsive release of DOX over a period of 96 h compared to that of CS‐MMT‐DOX nanocarriers at pH 5.4. Based on the Korsmeyer‐Peppas model, there was a controlled DOX release at pH 5.4, while no diffusion was observed at pH 7.4, indicating fewer side effects. MTT assay showed that the cytotoxicity of DOX‐loaded CS‐MMT‐NCQDs hydrogel nanocomposite was significantly higher than those of free DOX (p < 0.001) and CS‐MMT‐NCQDs (p < 0.001) on MCF‐7 cells. Flow cytometry results demonstrated that a higher apoptosis induction achieved after incorporating NCQDs nanoparticles into CS‐MMT‐DOX nanocarrier. These findings suggest that the DOX‐loaded nanocomposite is a promising candidate for the targeted treatment of cancer cells.

The acidic characteristic of the tumor site is one of the most well‐known features and provides a series of opportunities for cancer‐specific theranostic strategies. In this regard, pH‐responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI‐guided theranostic nanoplatforms for tumor‐specific treatments. Therefore, various MRI‐based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH‐responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH‐responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH‐responsiveness for cancer diagnosis and therapy are discussed. pH‐responsive theranostic nanoplatforms have provided a great opportunity in the combat with cancer. Herein, we summarize the recent progress in pH‐responsive theranostic nanoplatforms that integrate magnetic resonance imaging‐based diagnostics and a variety of therapeutic modes for tumor detection, imaging, and therapy.

Oxidative stress induced by excess reactive oxygen species (ROS) is a primary pathogenic cause of acute kidney injury (AKI). Development of an effective antioxidation system to mitigate oxidative stress for alleviating AKI remains to be investigated. This study presents the synthesis of an ultra‐small Platinum (Pt) sulfur cluster (Pt5.65S), which functions as a pH‐activatable prefabricated nanozyme (pre‐nanozyme). This pre‐nanozyme releases hydrogen sulfide (H2S) and transforms into a nanozyme (Ptzyme) that mimics various antioxidant enzymes, including superoxide dismutase and catalase, within the inflammatory microenvironment. Notably, the Pt5.65S pre‐nanozyme exhibits an endo‐exogenous synergy‐enhanced antioxidant therapeutic mechanism. The Ptzyme reduces oxidative damage and inflammation, while the released H2S gas promotes proneurogenesis by activating Nrf2 and upregulating the expression of antioxidant molecules and enzymes. Consequently, the Pt5.65S pre‐nanozyme shows cytoprotective effects against ROS/reactive nitrogen species (RNS)‐mediated damage at remarkably low doses, significantly improving treatment efficacy in mouse models of kidney ischemia‐reperfusion injury and cisplatin‐induced AKI. Based on these findings, the H2S‐generating pre‐nanozyme may represent a promising therapeutic strategy for mitigating inflammatory diseases such as AKI and others. This study presents a novel ultrasmall Pt5.65S pre‐nanozyme that releases hydrogen sulfide and exhibits inducible antioxidant enzyme‐like activity in an acidic and inflammatory microenvironment for managing acute kidney injury by promoting Nrf2 activation and mitigating oxidative damage.

Alginate (Alg) and bacterial nanocellulose (BNC) have exhibited great potential in biomedical applications, especially wound dressing. Non-toxicity and a moisture-maintaining nature are common features making them favorable for functional dressing fabrication. BNC is a natural biopolymer that promotes major advances to the current and future biomedical materials, especially in a flat or tubular membrane form with excellent mechanical strength at hydrated state. The main drawback limiting wide applications of both BNC and Alg is the lack of antibacterial activity, furthermore, the inherent poor mechanical property of Alg leads to the requirement of a secondary dressing in clinical treatment. To fabricate composite dressings with antibacterial activity and better mechanical properties, sodium alginate was efficiently incorporated into the BNC matrix using a time-saving vacuum suction method followed by cross-linking through immersion in separate solutions of six cations (manganese, cobalt, copper, zinc, silver, and cerium). The results showed the fabricated composites had not only pH-responsive antibacterial activities but also improved mechanical properties, which are capable of acting as smart dressings. All composites showed non-toxicity toward fibroblast cells. Rat model evaluation showed the skin wounds covered by the dressings healed faster than by BNC.

Despite significant advances in cancer treatment, several challenges persist in optimizing effective cargo delivery, including enhancing bioavailability, improving targeted delivery, and overcoming biological barriers for improved tumor tissue penetration. There is an urgent need for versatile carriers capable of multi‐functional targeting without compromising functionality. Here, we report a dual surface modification strategy to enhance the therapeutic efficacy of microrobotic platforms, through controlled, site‐specific drug release. This dual functionalization integrates two distinct pH‐sensitive polymeric nanoreservoirs with different membrane permeability. One nanoreservoir is engineered to release an antitumor agent ‐curcumin‐ in response to the acidic tumor microenvironment, while the second is designed to degrade the tumor extracellular matrix via enzymatic activity, facilitating enhanced diffussion of the therapeutic agent. This dual surface modification approach represents a significant advancement in the customizable integration of multifunctional nanoreservoirs. By leveraging dual compartmentalization, it prevents deactivation and cross‐process interference, enabling precise nanoscale combination therapies for microrobotic cancer treatment. These surface‐engineered microrobots hold promise for overcoming physiological barriers, ensuring stable cargo transport, and broadening the applicability of microrobotic platforms across diverse cancer types. A microcarrier with dual surface modification integrates two distinct pH‐sensitive nanoreservoirs, enabling precise, site‐specific drug delivery and potential extracellular matrix degradation. This dual functionalization strategy ensures the separation of therapeutic functions, effectively preventing cross‐process interference and aiming synergistic nanoscale combination therapies. This multifunctional system demonstrates strong potential for microrobotic applications in targeted cancer therapy, offering a robust and adaptable approach to enhance therapeutic efficacy.

The physiological milieu of healthy skin is slightly acidic, with a pH value between 4 and 6, whereas for skin with chronic or infected wounds, the pH value is above 7.3. As testing pH value is an effective way to monitor the status of wounds, a novel smart hydrogel wound patch incorporating modified pH indicator dyes was developed in this study. Phenol red (PR), the dye molecule, was successfully modified with methacrylate (MA) to allow a copolymerization with the alginate/polyacrylamide (PAAm) hydrogel matrix. This covalent attachment prevented the dye from leaching out of the matrix. The prepared pH-responsive hydrogel patch exhibited a porous internal structure, excellent mechanical property, and high swelling ratio, as well as an appropriate water vapour transmission rate. Mechanical responses of alginate/P(AAm-MAPR) hydrogel patches under different calcium and water contents were also investigated to consider the case of exudate accumulation into hydrogels. Results showed that increased calcium amount and reduced water content significantly improved the Young’s modulus and elongation at break of the hydrogels. These characteristics indicated the suitability of hydrogels as wound dressing materials. When pH increased, the color of the hydrogel patches underwent a transition from yellow (pH 5, 6 and 7) to orange (7.4 and 8), and finally to red (pH 9). This range of color change matches the clinically-meaningful pH range of chronic or infected wounds. Therefore, our developed hydrogels could be applied as promising wound dressing materials to monitor the wound healing process by a simple colorimetric display, thus providing a desirable substrate for printed electronics for smart wound dressing.

Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be amplified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors’ views for the future of the field are also presented.

Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms. To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition. CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model. The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of . Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice. Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy.