Janus and Amphiphilic MoS2 2D Sheets for Surface-Directed Orientational Assemblies toward Ex Vivo Dual Substrate Release.

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight (MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

Size-dependent magnetomechanically enhanced photothermal antibacterial effect of Fe3O4@Au/PDA nanodurian.

The global health crisis of bacterial resistance to antibiotics requires innovative antibacterial strategies. One promising solution is the exploitation of multifunctional nanoplatforms based on non-resistant antibacterial mechanisms. This work reports a novel Fe3O4@Au/polydopamine (PDA) nanodurian with excellent photothermal-magnetomechanic synergistic antibacterial effects. The one-step formed Au/PDA hybrid shell provides good photothermal properties and spiky surfaces for enhanced magnetomechanic effects. Upon near-infrared (NIR) irradiation, the Fe3O4@Au/PDA nanodurian (200 µg mL-1) achieved nearly 100% antibacterial effect against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The efficiency of photothermal antimicrobial activity was further enhanced by the application of a rotating magnetic field (RMF), with the sterilization efficiency being increased by up to more than a half compared to the action alone. Interestingly, the size of the nanodurian has a significant impact on the synergistic sterilization effect, with larger particles showing a superior performance due to stronger chain-like structures in the magnetic field. Finally, the Fe3O4@Au/PDA nanodurian also demonstrates effective biofilm removal, with larger particles exhibiting the best eradication effect under the photothermal-magnetomechanic treatment. Overall, this magnetic field enhanced photothermal antibacterial strategy provides a promising broad-spectrum antimicrobial solution to combat bacterial infections. Thus, it possesses great potential in future nanomedicine and pollution treatment.

Wearable Safeguarding Leather Composite with Excellent Sensing, Thermal Management, and Electromagnetic Interference Shielding.

This work illustrates a "soft-toughness" coupling design method to integrate the shear stiffening gel (SSG), natural leather, and nonwoven fabrics (NWF) for preparing leather/MXene/SSG/NWF (LMSN) composite with high anti-impact protecting, piezoresistive sensing, electromagnetic interference (EMI) shielding, and human thermal management performance. Owing to the porous fiber structure of the leather, the MXene nanosheets can penetrate leather to construct a stable 3D conductive network; thus both the LM and LMSN composites exhibit superior conductivity, high Joule heating temperature, and an efficient EMI shielding effectiveness. Due to the excellent energy absorption of the SSG, the LMSN composites possess a huge force-buffering (about 65.5%), superior energy dissipation (above 50%), and a high limit penetration velocity of 91 m s-1 , showing extraordinary anti-impact performance. Interestingly, LMSN composites possess an unconventional opposite sensing behavior to piezoresistive sensing (resistance reduction) and impact stimulation (resistance growing), thus they can distinguish the low and high energy stimulus. Ultimately, a soft protective vest with thermal management and impact monitoring performance is further fabricated, and it shows a typical wireless impact-sensing performance. This method is expected to have broad application potential in the next-generation wearable electronic devices for human safeguarding.

NIR-induced improvement of catalytic activity and antibacterial performance over AuAg nanorods in Rambutan-like Fe3O4@AgAu@PDA magnetic nanospheres.

Pathogenic bacteria and difficult-to-degrade pollutants in water have been serious problems that always plague people. Therefore, finding a "one stone-two birds" method that can quickly catalyze the degradation of pollutants and show effective antibacterial behavior become an urgent requirement. This work reports a facile one-step strategy for fabricating a Rambutan-like Fe3O4@AgAu@PDA (Fe3O4@AgAu@Polydopamine) core/shell nanosphere with both catalytic and antibacterial activities which can be critically improved by externally applying an NIR laser irradiation (NIR, 808 nm) and a rotating magnetic field. Typically, the Rambutan-like Fe3O4@AgAu@PDA nanosphere have a rather rough surface due to the AuAg bimetallic nanorods sandwiched between the Fe3O4 core and the PDA shell. Owing to the penetrated PDA shell, AgAu nanorods show high and magnetically recyclable photothermal-enhanced catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol and they can also be applied to initiate TMB oxidation under the help of NIR heating condition. Moreover, Fe3O4@AgAu@PDA shows a moderate antibacterial activity due to the weak release of Ag+. Under applying a rotating external magnetic field, the rough-surface Fe3O4@AgAu@PDA nanospheres produce a controllable magnetolytic force on the bacterial due to their good affinity. As a result, the Fe3O4@AgAu@PDA nanospheres show a "magnetolytic-photothermal-Ag+" synergistic antibacterial behavior against E. coli and S. aureus.

One-Pot Preparation of Cetylpyridinium Chloride-Containing Nanoparticles for Biofilm Eradication.

Quaternary ammonium compounds (QACs) have been widely used due to their excellent antimicrobial activity. However, using the technology where nanomaterials are employed as drug carriers to deliver QAC drugs has not been fully explored. In this study, mesoporous silica nanoparticles (MSNs) with short rod morphology were synthesized in a one-pot reaction using an antiseptic drug cetylpyridinium chloride (CPC). CPC-MSN were characterized via various methods and tested against three bacterial species (Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis), which are associated with oral infections, caries, and endodontic pathology. The nanoparticle delivery system used in this study prolonged the release of CPC. The manufactured CPC-MSN effectively killed the tested bacteria within the biofilm, and their size allowed them to penetrate into dentinal tubules. This CPC-MSN nanoparticle delivery system demonstrates potential for applications in dental materials.

A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses.

HYPOTHESIS: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare. EXPERIMENTS: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs. FINDINGS: The in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1ß. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer.

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 µM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.

π-Stacking Stopper-Macrocycle Stabilized Dynamically Interlocked [2]Rotaxanes.

The synthesis of mechanically interlocked molecules is valuable due to their unique topologies. With π-stacking intercomponent interaction, e.g., phenanthroline and anthracene, novel [2]rotaxanes have been synthesized by dynamic imine clipping reaction. Their X-ray crystal structures indicate the π-stackings between the anthracene moiety (stopper) on the thread and the (hetero)aromatic rings at the macrocycle of the rotaxanes. Moreover, the length of glycol chains affects the extra π-stacking intercomponent interactions between the phenyl groups and the dimethoxy phenyl groups on the thread. Dynamic combinatorial library has shown at best 84% distribution of anthracene-threaded phenanthroline-based rotaxane, coinciding with the crystallography in that the additional π-stacking intercomponent interactions could increase the thermodynamic stability and selectivity of the rotaxanes.

Citrate-Coated Magnetic Polyethyleneimine Composites for Plasmid DNA Delivery into Glioblastoma.

Several ternary composites that are based on branched polyethyleneimine (bPEI 25 kDa, polydispersity 2.5, 0.1 or 0.2 ng), citrate-coated ultrasmall superparamagnetic iron oxide nanoparticles (citrate-NPs, 8-10 nm, 0.1, 1.0, or 2.5 µg), and reporter circular plasmid DNA pEGFP-C1 or pRL-CMV (pDNA 0.5 µg) were studied for optimization of the best composite for transfection into glioblastoma U87MG or U138MG cells. The efficiency in terms of citrate-NP and plasmid DNA gene delivery with the ternary composites could be altered by tuning the bPEI/citrate-NP ratios in the polymer composites, which were characterized by Prussian blue staining, in vitro magnetic resonance imaging as well as green fluorescence protein and luciferase expression. Among the composites prepared, 0.2 ng bPEI/0.5 µg pDNA/1.0 µg citrate-NP ternary composite possessed the best cellular uptake efficiency. Composite comprising 0.1 ng bPEI/0.5 µg pDNA/0.1 µg citrate-NP gave the optimal efficiency for the cellular uptake of the two plasmid DNAs to the nucleus. The best working bPEI concentration range should not exceed 0.2 ng/well to achieve a relatively low cytotoxicity.

MALDI-MS Imaging Analysis of Noninflammatory Type III Rotaxane Dendrimers.

Rotaxane dendrimers with hyperbranched macromolecular interlocked structures and size modulation capacity demonstrate drug binding and release ability upon external stimuli. Mass spectrometry imaging (MSI) can offer the high-throughput screening of endogenous/exogenous compounds. Herein, we reported a novel method to display the in situ spatial distribution of label-free monodispersed type III rotaxane dendrimers (RDs) G1 (first generation, size ∼1.5 nm) and G2 (second generation, size ∼5 nm) that were explored as potential drug vehicles in spleen tissue by using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-MSI). Experimental results indicated that the trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB) matrix exhibited the best performance for monodispersed type III RDs G1 and G2. The optimized method was successfully applied to map the in vivo spatial distribution of type III RDs G1 and G2 in the spleen from intraperitoneally injected mice. The MALDI-MSI images revealed that RDs G1 and G2 were relatively stable in the spleen within 24 h after administration. It was found that the identified type III RDs G1 and G2 penetrated through the tunica serosa and were predominantly localized in red pulp regions of spleens. They were also mapped in a marginal zone of spleens simultaneously. There was almost no toxicity of type III RDs G1 and G2 to mice spleens from the H&E results. Furthermore, the type III RDs did not induce the expression of inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) or THP-1 monocytes. The MSI analysis not only demonstrated its ability to image select rotaxane dendrimers in a rapid and efficient manner but also provided tremendous assistance on the applications of the further treatment of cancerous tissue as safe drug carriers. Furthermore, the new strategy demonstrated in this study could be applied on other label-free mechanically interlocked molecules, molecular machines, and macromolecules, which opened a new path to evaluate the toxicological and pharmacokinetic characteristics of these novel materials at the suborgan level.

Selective detection of sulfide in human lung cancer cells with a blue-fluorescent "ON-OFF-ON" benzimidazole-based chemosensor ensemble.

A completely water-soluble, high quantum yield blue-fluorescent benzimidazole derivative (AQ), containing a rigid benzimidazole-thiophene structure, was synthesized. Among 21 metal ions, the fluorescence of AQ was selectively turned off by Cu2+ to form an AQ-Cu2+ ensemble. Thereafter, the fluorescence of the AQ-Cu2+ ensemble was turned on by sulfide (S2-) with high selectivity and sensitivity in pure water solution. In comparison with AQ-Ag+ and AQ-Hg2+ ensembles, AQ-Cu2+ was the only ensemble that was capable of detecting a sulfide anion. Also, the fluorescence intensity of AQ was linearly proportional to the concentration of Cu2+ and S2-. Both Cu2+ and S2- were detected within a minute in vitro. Moreover, AQ worked best in the pH range of 5-10 and had a limit of detection of 50 nM and 354 nM for Cu2+ and S2- respectively. It was employed for the detection of sulfide in human lung cancer A549 cells with low cytotoxicity.

A BODIPY-based fluorescent sensor for the detection of Pt2+ and Pt drugs.

A BODIPY-based fluorescent sensor PS with an NO4S2 podand ligand was studied for the selective detection of Pt2+ over 21 cations as well as selected platinum drugs in aqueous medium. The platinum sensor PS shows 28-fold, 22-fold and 14-fold fluorescence turn-on enhancements to Pt2+, cisplatin and nedaplatin, and was thereby employed to detect platinum drugs in A-549 human lung cancer cells.

Highly selective detection of Pd2+ ion in aqueous solutions with rhodamine-based colorimetric and fluorescent chemosensors.

In this study, we report a new class of rhodamine-based fluorescent sensors for highly selective and sensitive detection of Pd2+ ions in aqueous medium. A rhodamine-based palladium sensor RPS and a coumarin-rhodamine Förster resonance energy transfer (FRET)-pair based palladium sensor FPS were synthesized with the designed podand ligand for Pd2+ ion recognition. They showed both colorimetric change and fluorometric change in the presence of Pd2+ ion due to the opening of their spirolactam rings. Both chemosensors are highly selective to Pd2+ over the other 24 different metal ions and they are selective to palladium species in +2 oxidation state, RPS showed a 70-fold fluorescent turn-on while FPS showed a 1.75-fold ratiometric change at I599/I470. Furthermore, RPS showed low cell cytotoxicity and it was successfully used to image Pd2+ in BEAS-2B lung epithelial cells. © 2019 Elsevier Science. All rights reserved.

Mass spectrometry imaging and monitoring of in vivo glutathione-triggered cisplatin release from nanoparticles in the kidneys.

An increasing number of studies have reported the use of various nanoparticles to encapsulate cisplatin, a frontline chemotherapeutic drug against a broad-spectrum of cancers, for overcoming its inherent drawbacks in clinical applications. Nevertheless, few analytical methods or instruments could provide the precise distribution information on this platinum drug in biological tissues. Herein, we provide the first evidence of applying matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to assess the spatial distribution of cisplatin released from the cell-penetrating poly(disulfide) (CPD)-modified hollow iron oxide nanoparticles (hFe3O4-MPS-CPD) at the kidneys via an in situ glutathione (GSH) responsive mode. The cisplatin released from the nanoparticles triggered by GSH was successfully examined as [Pt(DDTC)2]+ (m/z 491.01) and [Pt(DDTC)3]+ (m/z 639.04) by MALDI-MS after derivatization using diethyldithiocarbamate. The in situ spatial distribution of [Pt(DDTC)2]+ and [Pt(DDTC)3]+ in the kidneys was then mapped using MALDI-MSI. This study presents an optimized analytical approach to evaluate and map the metallodrug in biological tissue samples in an efficient and convenient manner, offering great assistance in investigating the biodistribution of cisplatin delivered by nanoparticles, and sheds light on facilitating the studies of the pharmacokinetics of cisplatin in biomedical research.

Polydopamine protected hollow nanosphere with AuAg-nanoframe-core@Carbon@AuAg-nanocrystals-satellite hybrid nanostructure (AuAg@C@AuAg/PDA) for enhancing nanocatalysis.

This work reported a facile method for fabricating multi-layered polydopamine (PDA) encapsulated AuAg@C@AuAg core/shell nanosphere with a hollow interior. During the synthetic process, the preliminary Ag@C nanosphere is easily covered by an AuAg/PDA hybrid layer through the in situ redox-oxidized polymerization to form the Ag-AuAg@C@AuAg/PDA precursor, in which the AuAg bimetallic nanocrystals are simultaneously obtained via the electrochemical substitution reaction. After etching the residue Ag core, the final AuAg@C@AuAg/PDA hybrid nanosphere is achieved and the inner AuAg shows a unique nanoframe-like nanostructure. The carbon shell plays an important role for the formation and structure evolution of the AuAg@C@AuAg/PDA, and the composition can be modulated by varying the polymerization process. Owing to the well distributed AuAg nanocrystals and inner AuAg nanoframes, the AuAg@C@AuAg/PDA shows better performance than Ag-AuAg@C@AuAg/PDA precursor in catalyzing 4-nitrophenol, and the rate constant (K) to catalyst weight ratio reaches as high as 3.63 min-1 •mg-1. As a result, this work not only offers a hybrid bi-metallic nanocatalyst with excellent performance, but also has valuable implications for compositional modulation of hollow interior multi-layered nanostructure in adsorption, drug delivery, and nanocatalysis.

Intrapulmonary Cellular-Level Distribution of Inhaled Nanoparticles with Defined Functional Groups and Its Correlations with Protein Corona and Inflammatory Response.

Concerns over the health risks associated with airborne exposure to ultrafine particles [PM0.1, or nanoparticles (NPs)] call for a comprehensive understanding in the interactions of inhaled NPs along their respiratory journey. We prepare a collection of polyethylene glycol-coated gold nanoparticles that bear defined functional groups commonly identified in atmospheric particulates (Au@PEG-X NPs, where X = OCH3, COOH, NH2, OH, or C12H25). Regardless of the functional group, these ∼50 nm NPs remain colloidally stable following aerosolization and incubation in bronchoalveolar lavage fluid (BALF), without pronouncedly crossing the air-blood barrier. The type of BALF proteins adhered onto the NPs is similar, but the composition of protein corona depends on functional group. By subjecting Balb/c mice to inhalation of Au@PEG-X NPs for 6 h, we demonstrate that the intrapulmonary distribution of NPs among the various types of cells (both found in BALF and isolated from the lavaged lung) and the acute inflammatory responses induced by inhalation are sensitive to the functional group of NPs and postinhalation period (0, 24, or 48 h). By evaluating the pairwise correlations between the three variables of "lung-nano" interactions (protein corona, intrapulmonary cellular-level distribution, and inflammatory response), we reveal strong statistical correlations between the (1) fractions of albumin or carbonyl reductase bound to NPs, (2) associations of inhaled NPs to neutrophils in BALF or macrophages in the lavaged lung, and (3) level of total protein in BALF. Our results provide insights into the effect of functional group on lung-nano interactions and health risks associated with inhalation of PM0.1.

Red-Emissive Guanylated Polyene-Functionalized Carbon Dots Arm Oral Epithelia against Invasive Fungal Infections.

Oral candidiasis as a highly prevalent and recurrent infection in medically compromised individuals is mainly caused by the opportunistic fungal pathogen Candida albicans. This epithelial infection, if not controlled effectively, can progress to life-threatening systemic conditions and complications. The efficacy of current frontline antifungals is limited due to their poor bioavailability and systemic toxicity. As such, an efficient intervention is essential for controlling disease progression and recurrence. Herein, a theranostic nanoplatform (CD-Gu+-AmB) was developed to track the penetration of antifungals and perturb the invasion of C. albicans at oral epithelial tissues, via decorating the homemade red-emissive carbon dots (CD) with positively charged guanidine groups (Gu+) followed by conjugation with antifungal polyene (amphotericin B, AmB) in a reacting site-controllable manner. The generated CD-Gu+-AmB favorably gathered within the Candida cells and exhibited potent antifungal effects in both planktonic and biofilm forms. It selectively accumulated in the nuclei of human oral keratinocytes and exhibited undetectable toxicity to the host cells. Moreover, we reported for the first time the penetration and exfoliation profiles of CD in a three-dimensional organotypic model of human oral epithelial tissues, demonstrating that the extra- and intracellular accumulation of CD-Gu+-AmB effectively resisted the invasion of C. albicans by forming a "shielding" layer throughout the entire tissue. This study establishes a multifunctional CD-based theranostic nanoplatform functioning as a traceable and topically applied antifungal to arm oral epithelia, thereby shedding light on early intervention of mucosal candidiasis for oral and general health.

Type III-C rotaxane dendrimers: synthesis, dual size modulation and in vivo evaluation.

Type III-C rotaxane dendrimers were synthesized by a divergent approach. Dual shuttling behavior and size modulation were observed from non-methylated/methylated rotaxane dendrimers under the same external stimuli. The biological distribution of dendrimers in C57BL/6J mice determined by MALDI-TOF-MS shows predominant accumulation in the spleen and liver. Drug encapsulations with chlorambucil and lithocholic acid were demonstrated.

Promoting the Delivery of Nanoparticles to Atherosclerotic Plaques by DNA Coating.

Many nanoparticle-based carriers to atherosclerotic plaques contain peptides, lipoproteins, and sugars, yet the application of DNA-based nanostructures for targeting plaques remains infrequent. In this work, we demonstrate that DNA-coated superparamagnetic iron oxide nanoparticles (DNA-SPIONs), prepared by attaching DNA oligonucleotides to poly(ethylene glycol)-coated SPIONs (PEG-SPIONs), effectively accumulate in the macrophages of atherosclerotic plaques following an intravenous injection into apolipoprotein E knockout (ApoE-/-) mice. DNA-SPIONs enter RAW 264.7 macrophages faster and more abundantly than PEG-SPIONs. DNA-SPIONs mostly enter RAW 264.7 cells by engaging Class A scavenger receptors (SR-A) and lipid rafts and traffic inside the cell along the endolysosomal pathway. ABS-SPIONs, nanoparticles with a similarly polyanionic surface charge as DNA-SPIONs but bearing abasic oligonucleotides also effectively bind to SR-A and enter RAW 264.7 cells. Near-infrared fluorescence imaging reveals evident localization of DNA-SPIONs in the heart and aorta 30 min post-injection. Aortic iron content for DNA-SPIONs climbs to the peak (∼60% ID/g) 2 h post-injection (accompanied by profuse accumulation in the aortic root), but it takes 8 h for PEG-SPIONs to reach the peak aortic amount (∼44% ID/g). ABS-SPIONs do not appreciably accumulate in the aorta or aortic root, suggesting that the DNA coating (not the surface charge) dictates in vivo plaque accumulation. Flow cytometry analysis reveals more pronounced uptake of DNA-SPIONs by hepatic endothelial cells, splenic macrophages and dendritic cells, and aortic M2 macrophages (the cell type with the highest uptake in the aorta) than PEG-SPIONs. In summary, coating nanoparticles with DNA is an effective strategy of promoting their systemic delivery to atherosclerotic plaques.

Noninvasive real-time monitoring of local drug release using nano-Au-absorbed self-decomposable SiO2 carriers.

Real time monitoring of drug release at specific local sites by a non-invasive imaging method is critical in patient-specific drug administration in order to avoid insufficient or excess drug dosing. In the present work, we designed a specific carrier system for such a purpose using self-decomposable SiO2 nanoparticles (NPs) with the drug being loaded in the center and Au NPs on the SiO2 NPs as the imaging agent. We discovered a correlation between the drug release from the carrier and the morphological evolution of Au NPs, which also left the carrier and changed their aggregation states along with the drug release process. This finding enabled the real time monitoring of the drug release at local sites (e.g. tumor) in a quantitative manner by recording the CT signal evolution of the Au NPs, as demonstrated in vivo using mice bearing Colo-205 xenografts. The present work provided a promising platform for non-invasive real time tracking on the localized drug release, enabling a variety of personalized therapeutic applications.