Steering Sulfur Reduction Pathways via Cisplatin Enables High Performance in Lithium-Sulfur Batteries.

The sulfur reduction reaction (SRR) is an attractive 16-electron transfer process that endows Li-S batteries with a theoretical capacity of 1,672 mAh g-1. However, the slow kinetics and complex pathways of the SRR cause the shuttling of soluble polysulfides (PSs), thus fast capacity fading. Here, we report using cisplatin (cis-Pt) as a novel mediator to improve the SRR kinetics and a molecular probe to identify the SRR pathways. We show that cis-Pt with a reductive Pt2+ center can directly slice the S-S bonds of PSs, leading to enhanced charge transfer kinetics, guided SRR pathways, and depth conversion of PSs to Li2S. With cis-Pt added, Li-S coin cells deliver a maximum specific capacity of 1,437 mAh g-1 and a capacity decay of 0.017% per cycle after 1000 cycles, while a pouch cell with a practical electrolyte-sulfur ratio (2.5 µl mg-1) exhibits a high energy density of 318.8 Wh kg-1. Our mechanistic studies reveal that cis-Pt steers the cathodic SRR pathways by generating redox active cis-Pt/PSs complexes, enabling the replacement of the sluggish SRR with a faster redox cycling of Pt4+/Pt2+ pairs. These findings provide insights into the rational design of functional mediators for tackling the cathodic challenges inside Li-S batteries.

Unexpected Emergence of Carbon-Centered Radicals from Piezoelectric Effect in Oleic Acid-Capped BaTiO3.

The utilization of alkyl radicals (•R) for hypoxic tumor therapy has great prospects due to its O2-independence and high reactivity. However, correlational initiators for in vivo activation remain scarce. Here, we report that ultrasound excitation of oleic acid-capped BaTiO3 (OA@BaTiO3) can result in an •R cascade and hence a means to conquer hypoxic tumors. Mechanistic studies find that the •R signal disappears when OA@BaTiO3 undergoes acid washing post-treatment, which is a common procedure for removing the unwanted byproduct BaCO3. Combined with the infrared spectrum analysis, acid treatment was proven to weaken the peaks at 2840-2970 cm-1 characteristic of -CH2- and terminal -CH3 stretching vibration of OA. There is compelling evidence that high temperature thermal oxidation of OA involves the generation of •R. Thus, acid washing is considered to remove the loosely bound yet catalytically active OA. And piezoelectric BaTiO3, a potential electron-hole redox catalyst, can sensitize these OA molecules and disintegrate them to •R. This unexpected discovery provides us with a distinctive mentality to seek diverse •R initiators for tumor ablation, as well as an additional perspective on the postprocessing of synthetic materials.

Combination of Rapid Intrinsic Activity Measurements and Machine Learning as a Screening Approach for Multicomponent Electrocatalysts.

Machine learning (ML) coupled with quantum chemistry calculations predicts catalyst properties with high accuracy; however, ML approaches in the design of multicomponent catalysts primarily rely on simulation data because obtaining sufficient experimental data in a short time is difficult. Herein, we developed a rapid screening strategy involving nanodroplet-mediated electrodeposition using a carbon nanocorn electrode as the support substrate that enables complete data collection for training artificial intelligence networks in one week. The inert support substrate ensures intrinsic activity measurement and operando characterization of the irreversible reconstruction of multinary alloy particles during the oxygen evolution reaction. Our approach works as a closed loop: catalyst synthesis-in situ measurement and characterization-database construction-ML analysis-catalyst design. Using artificial neural networks, the ML analysis revealed that the entropy values of multicomponent catalysts are proportional to their catalytic activity. The catalytic activities of high-entropy systems with different components varied little, and the overall catalytic activity was greater than that of the medium-low-entropy system. These findings will serve as a guideline for the design of catalysts.

Near-Infrared Light-Enhanced Generation of Hydroxyl Radical for Cancer Immunotherapy.

Hydroxyl radical (• OH) as a highly oxidizing reactive oxygen species can induce immunogenic cell death (ICD) in cancer treatment. However, high-efficiency cancer immunotherapy is still a huge challenge due to the low • OH generation efficiency in the tumor microenvironment, resulting in insufficient immunogenicity and the poor immune response. Here, a near-infrared (NIR) light-enhanced • OH generation strategy is developed for cancer immunotherapy by using a copper-based metal-organic framework (Cu-DBC) nanoplatform. With this strategy, the generation efficiency of • OH under NIR irradiation is increased 7.34 times than that without NIR irradiation, which induces robust ICD and immune response, thus leading to primary tumor elimination and the inhibition of distant tumor growth and tumor lung metastasis. Experimental results show that Cu-DBC can induce • OH boosting through photothermal (PT)-enhanced Cu-catalytic Fenton-like reaction and photocatalytic electron transfer under NIR light irradiation to amplify tumor ICD for immunotherapy.

Rational Utilization of Black Phosphorus Nanosheets to Enhance Palladium-Mediated Bioorthogonal Catalytic Activity for Activation of Therapeutics.

Pd-catalyzed chemistry has played a significant role in the growing subfield of bioorthogonal catalysis. However, rationally designing Pd nanocatalysts that show outstanding catalytic activity and good biocompatibility poses a great challenge. Herein, we propose an innovative strategy through exploiting black phosphorous nanosheets (BPNSs) to enhance Pd-mediated bioorthogonal catalytic activity. Firstly, the electron-donor properties of BPNSs enable in situ growth of Pd nanoparticles (PdNPs) on it. Meanwhile, due to the superb capability of reducing PdII , BPNSs can act as hard nucleophiles to accelerate the transmetallation in the decaging reaction process. Secondly, the lone pair electrons of BPNSs can firmly anchor PdNPs on their surface via Pd-P bonds. This design endows Pd/BP with the capability to retard tumor growth by activating prodrugs. This work proposes new insights into the design of heterogeneous transition-metal catalysts (TMCs) for bioorthogonal catalysis.

Engineering a synergistic antioxidant inhibition nanoplatform to enhance oxidative damage in tumor treatment.

The antioxidant system of tumor cells severely impairs reactive oxygen species (ROS)-mediated tumor therapy. Despite extensive attempts to attenuate the antioxidant capacity by eliminating ROS scavengers such as glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) over-expressed in the tumor microenvironment can regenerate GSH from glutathione disulfide (GSSG), hence weakening ROS-induced oxidative damage. Therefore, engineering a nanoplatform capable of depleting both NADPH and GSH is extremely significant for improving ROS-mediated tumor treatment. Herein, a synergetic antioxidant inhibition strategy is proposed to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. In this context, both porous Prussian blue nanoparticles (PPB NPs) and cisplatin prodrug [cis-Pt (IV)] in the nanoplatform can oxidize GSH to directly reduce GSH levels, while PPB NPs also enable NADPH depletion by peroxidase-mimicking to impair GSH regeneration. Furthermore, PPB NPs with catalase-mimicking activity catalyze H2O2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting singlet oxygen (1O2) production by Chlorin e6 (Ce6) for enhancing oxidative damage. Experimental results prove that the nanoplatform, denoted as PPB-Ce6-Pt, can induce remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of Food Drug Administration (FDA)-approved materials make PPB-Ce6-Pt have great potential for practical applications. STATEMENT OF SIGNIFICANCE: The antioxidant system in tumor cells disables ROS-mediated tumor therapy. Besides, extensive attempts aim at depleting GSH without considering their regeneration. Therefore, we developed a synergetic strategy to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. PPB-Ce6-Pt nanoplatform could not only directly reduce GSH levels but also deplete NADPH by peroxidase-mimicking to impair GSH regeneration. In addition, PPB-Ce6-Pt nanoplatform could catalyze H2O2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting 1O2 production by Chlorin e6 (Ce6) for increasing oxidative damage. Then, intracellular ROS boost and redox dyshomeostasis induced remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of biosafety materials made the nanoplatform have great potential for practical applications.

Facile synthesis of nitrogen-doped carbon dots as sensitive fluorescence probes for selective recognition of cinnamaldehyde and l-Arginine/l-Lysine in living cells.

The disorder of amino acid metabolism and the abuse of small molecule drugs pose serious threats to public health. However, due to the limitations of existing detection technologies in sensing cinnamaldehyde (CAL) and l-Arginine/l-Lysine (l-Arg/l-Lys), there is an urgent need to develop new sensing strategies to meet the severe challenges currently facing. Herein, nitrogen-doped carbon dots (N-CDs) were developed using a simple one-pot hydrothermal carbonization method. These N-CDs exhibited numerous distinctive characteristics such as excellent photoluminescence, high water dispersibility, favorable biocompatibility, and superior chemical inertness. Strikingly, the as-prepared CDs as a highly efficient fluorescent probe possessed significant sensitivity and selectivity toward CAL and l-Arg/l-Lys over other analytes with a low detection limit of 58 nM and 16 nM/18 nM, respectively. The fluorescence of N-CDs could be quenched by CAL through an electron transfer process. Then, the strong electrostatic interaction between l-Arg/l-Lys and N-CDs induced the efficient fluorescence recovery. More importantly, the outstanding biosafety and excellent analyte-responsive fluorescence characteristics of N-CDs have also been verified in living cells as well as in serum and urine. Overall, the N-CDs had a wide application prospect in the diagnosis of amino acid metabolic diseases and small molecule drug sensing.

Gadolinium (III) doped carbon dots as dual-mode sensor for the recognition of dopamine hydrochloride and glutamate enantiomers with logic gate operation.

Dopamine hydrochloride (DH) and D-Glutamic acid (D-Glu) are important excitatory neurotransmitters, which are closely relative to central nervous system diseases. Therefore, it is critical to develop the sensitive and facile sensor to precisely monitor the changes of these neurotransmitters. Herein, the gadolinium-doped carbon dots (Gd-CDs) were synthesized by a low-cost and effortless one-pot solvothermal method. These CDs exhibited rapid and reliable fluorescent and colorimetric response signals towards DH and D-Glu. Interestingly, the fluorescence of Gd-CDs could be selectively quenched by DH owing to the fact that the Gd-CDs could coordinate with phenolic hydroxyl groups of DH. Moreover, the quench process was effectively inhibited because the D-Glu competitively coordinated with Gd-CDs-DH system to form a more stable complex. In fluorescence mode, the designed fluorescence sensor possessed an excellent linear relationship for DH in the range from 1 to 10 µM with a low detection limit of 1.26 nM, and the fluorescence could be selectively recovered by D-Glu. In colorimetric manner, DH and D-Glu could be detected by UV-Vis absorption spectrum in the range of 1-15 µM and 1-1.50 mM, respectively. Moreover, the proposed method could not only easily monitor the DH and D-Glu in aqueous solutions as well as mouse serum and human urine samples, but also be employed for detecting DH and D-Glu in cells. Fortunately, the fluorescent and colorimetric dual readout AND logic operation was successfully demonstrated in all-aqueous media. Accordingly, the prepared Gd-CDs hold the potential to become a promising nano-sensor for DH and D-Glu sensing in disease diagnosis areas.

SERS monitoring of photoinduced-enhanced oxidative stress amplifier on Au@carbon dots for tumor catalytic therapy.

Currently, artificial enzymes-based photodynamic therapy (PDT) is attractive due to its efficient capacity to change the immunosuppressive tumor microenvironment (TME). It is of great significance to study the therapeutic mechanism of novel artificial enzymes in TME through a monitoring strategy and improve the therapeutic effect. In this study, Au@carbon dots (Au@CDs) nanohybrids with a core-shell structure are synthesized, which not only exhibit tunable enzyme-mimicking activity under near-infrared (NIR) light, but also excellent surface-enhanced Raman scattering (SERS) properties. Therefore, Au@CDs show a good capability for monitoring NIR-photoinduced peroxidase-like catalytic processes via a SERS strategy in tumor. Moreover, the Au@CDs deplete glutathione with the cascade catalyzed reactions, thus elevating intratumor oxidative stress amplifying the reactive oxygen species damage based on the NIR-photoinduced enhanced peroxidase and glutathione oxidase-like activities, showing excellent and fast PDT therapeutic effect promoted by photothermal property in 3 min, finally leading to apoptosis in cancer cells. Through SERS monitoring, it is further found that after removing the NIR light source for 33 min, the reactive oxygen species (ROS) activity of the TME is counteracted and eliminated due to the presence of glutathione. This work presents a guidance to rationally design of artificial enzyme for ROS-involved therapeutic strategies and a new spectroscopic tool to evaluate the tumor catalytic therapy.

A mitochondria targeted cascade reaction nanosystem for improved therapeutic effect by overcoming cellular resistance.

Mitigating cellular resistance, which could enhance the sensitivity of tumor cells to treatment, is a promising approach for obtaining better therapeutic outcomes. However, the present designs of materials generally disregard this point, or only focus on a single specific resistance. Herein, a strategy based on a series of cascade reactions aiming to suppress multiple cellular resistances is designed by integrating photothermal and chemotherapy into a mitochondria targeted nanosystem (AuBPs@TD). The intelligent nanosystem is fabricated by modifying gold nanobipyramids (AuBPs) with triphenylphosphonium (TPP) functionalized dichloroacetic acid (DCA). TPP serves as a "navigation system" and facilitates the location of AuBPs@TD in the mitochondria. Moreover, the released DCA promoted by the photothermal effect of AuBPs, as the mitochondrial kinase inhibitor, could inhibit glycolysis, and lead to a repressed expression of heat shock protein 90, which is the main resistance protein in cancer cells against photothermal therapy (PTT). Thus, the photothermal antitumor effect can be significantly improved. For the other cascade passage, the hyperthermal atmosphere depresses the expression of P-glycoprotein, a protein associated with drug resistance, and consequently prevents DCA molecules from being expelled in return. Furthermore, the retained DCA molecules elevate the concentration of intracellular hydrogen peroxide, and due to the peroxidase-like activity of AuBPs, increased intracellular reactive oxygen species could be obtained to accelerate apoptosis. As a result, these cascade reactions lead to significant inhibition of cellular resistance and greatly improve the therapeutic performance. This work paves a new way for suppressing cellular resistance to achieve the desired therapeutic effect.

Mitochondria-Targeting Enhanced Phototherapy by Intrinsic Characteristics Engineered "One-for-All" Nanoparticles.

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.

Defect Engineering Enables Synergistic Action of Enzyme-Mimicking Active Centers for High-Efficiency Tumor Therapy.

Perusing redox nanozymes capable of disrupting cellular homeostasis offers new opportunities to develop cancer-specific therapy, but remains challenging, because most artificial enzymes lack enzyme-like scale and configuration. Herein, for the first time, we leverage a defect engineering strategy to develop a simple yet efficient redox nanozyme by constructing enzyme-mimicking active centers and investigated its formation and catalysis mechanism thoroughly. Specifically, the partial Fe doping in MoOx (donated as Fe-MoOv) was demonstrated to activate structure reconstruction with abundant defect site generation, including Fe substitution and oxygen vacancy (OV) defects, which significantly enable the binding capacity and catalytic activity of Fe-MoOv nanozymes in a synergetic fashion. More intriguingly, plenty of delocalized electrons appear due to Fe-facilitated band structure reconstruction, directly contributing to the remarkable surface plasmon resonance effect in the near-infrared (NIR) region. Under NIR-II laser irradiation, the designed Fe-MoOv nanozymes are able to induce substantial disruption of redox and metabolism homeostasis in the tumor region via enzyme-mimicking cascade reactions, thus significantly augmenting therapeutic effects. This study that takes advantage of defect engineering offers new insights into developing high-efficiency redox nanozymes.

An All-in-One Organic Semiconductor for Targeted Photoxidation Catalysis in Hypoxic Tumor.

Tumor hypoxia severely limits the therapeutic effects of photodynamic therapy (PDT). Although many methods for oxygen generation exist, substantial safety concerns, spatiotenporal uncontrollability, limited efficacy, and complicated procedures have compromised their practical application. Here, we demonstrate a biocompatiable all-in-one organic semiconductor to provide a photoxidation catalysis mechanism of action. A facile method is developed to produce gram-level C5 N2 nanoparticles (NPs)-based organic semiconductor. Under 650 nm laser irradiation, the semiconductor split water to generate O2 and simultaneously produce singlet oxygen (1 O2 ), showing that the photocatalyst for O2 evolution and the photosensitizer (PS) for 1 O2 generation could be synchronously achieved in one organic semiconductor. The inherent nucleus targeting capacity endows it with direct and efficient DNA photocleavage. These findings pave the way for developing organic semiconductor-based cancer therapeutic agents.

On-demand degradable magnetic resonance imaging nanoprobes.

Theranostic nanoprobes can potentially integrate imaging and therapeutic capabilities into a single platform, offering a new personalized cancer diagnostic tool. However, there is a growing concern that their clinical application is not safe, particularly due to metal-containing elements, such as the gadolinium used in magnetic resonance imaging (MRI). We demonstrate for the first time that the photothermal melting of the DNA duplex helix was a reliable and versatile strategy that enables the on-demand degradation of the gadolinium-containing MRI reporter gene from polydopamine (PDA)-based theranostic nanoprobes. The combination of chemotherapy (doxorubicin) and photothermal therapy, which leads to the enhanced anti-tumor effect. In vivo MRI tracking reveals that renal filtration was able to rapidly clear the free gadolinium-containing MRI reporter from the mice body. This results in a decrease in the long-term toxic effect of theranostic MRI nanoprobes. Our findings may pave the way to address toxicity issues of the theranostic nanoprobes.

Nanoscaled porphyrinic metal-organic framework for photodynamic/photothermal therapy of tumor.

Nanoagents achieving photodynamic therapy (PDT) and photothermal therapy (PTT) combination treatment with improved therapeutic effect are highly desirable. However, the incorporation of both PDT and PTT into a single nanoagent often requires multistep fabrication process. Herein, we report that photoactive porphyrin ligands have been successfully introduced into Zn-TCPP structure to construct the nanoagents that possesses photodynamic performance and photothermal performance simultaneously. Such a nanoagent enables the generation of single oxygen and heat under laser irradiation. Additionally, it exhibits satisfactory biocompatibility and high light toxicity against cancer cells. The current work provides a feasible approach to introduce both PDT and PTT into a single nanoplatform.

A C5 N2 Nanoparticle Based Direct Nucleus Delivery Platform for Synergistic Cancer Therapy.

Intracellular targeting has the same potential as tissue targeting to increase therapy efficacy, especially for drugs that are toxic to DNA. By adjusting intracellular traffic, we developed a novel direct-nucleus-delivery platform based on C5 N2 nanoparticles (NPs). Supramolecular interactions of C5 N2 NPs with the cell membrane enhanced cell uptake; abundant edge amino groups promoted fast and effective rupture of early endosomes; and the appropriate size of the NPs was also crucial for size-dependent nuclear entry. As a proof of concept, the platform was not only suitable for the effective delivery of molecular drugs/dyes (doxorubicin, hydroxycamptothecine, and propidium iodide) and MnO2 nanoparticles to the nucleus, but was also photoresponsive for nucleus-targeting photothermal therapy (PTT) and photodynamic therapy (PDT) to further greatly increase anticancer efficacy. This strategy might open the door to a new generation of nuclear-targeted enhanced anticancer therapy.

Delineating the tumor margin with intraoperative surface-enhanced Raman spectroscopy.

The failure of complete tumor resection during cancer surgery is a leading cause of lethal recurrence and metastasis. However, achieving accurate delineation of tumor margins intraoperatively remains extremely difficult because the infiltrated nature of a tumor usually gives an obscure margin and spreading microtumors. Recent studies show that surface-enhanced Raman scattering (SERS) has the potential to depict precisely the actual tumor extent with high sensitivity, specificity, and spatial resolution; thus providing a promising platform to improve the therapeutic efficiency. In this review, we discuss the recent progress in the use of SERS spectroscopy for intraoperative image-guided resection. We highlight key successes in the development of SERS tags and give insights into the design mechanism of rational SERS tags. We also discuss how to improve the performance of intraoperative navigation based on SERS and explore the challenges and future opportunities for the development of a more effective SERS-based platform. Graphical abstract ᅟ.

Plasmonic titanium nitride nanoparticles for in vivo photoacoustic tomography imaging and photothermal cancer therapy.

Titanium nitride, an alternative plasmonic material to gold with unique physiochemical properties, has been widely used in microelectronics, biomedical devices and food-contact applications. However, its potential application in the area of biomedicine has not been effectively explored. With the spectral match of their plasmon resonance band and the biological transparency window as well as good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging. Nevertheless, the photothermal performance of TiN NPs has not been investigated until now. Here, we presented the investigation of employing TiN NPs as photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided photothermal cancer therapy. Our experimental results showed that TiN NPs could strongly absorb the NIR light and provided up to 48% photothermal conversion efficiency. After PEGylation, the resultant nanoparticles demonstrated improved physiological stability and extensive blood retention. Following intravenously administration, they could simultaneously enhance the photoacoustic signals of the tumor region and destroy tumors in the tumor-bearing mouse model by taking advantage of the photothermal effect of the TiN NPs. Our findings highlighted the great potential of plasmonic TiN NPs in detection and treatment of cancer.

Targeted polydopamine nanoparticles enable photoacoustic imaging guided chemo-photothermal synergistic therapy of tumor.

Near infrared light responsive nanoparticles can transfer the absorbed NIR optical energy into heat, offering a desirable platform for photoacoustic (PA) imaging guided photothermal therapy (PTT) of tumor. However, a key issue in exploiting this platform is to achieve optimal combination of PA imaging and PTT therapy in single nanoparticle. Here, we demonstrate that the biodegradable polydopamine nanoparticles (PDAs) are excellent PA imaging agent and highly efficient for PTT therapy, thus enabling the optimal combination of PA imaging and PTT therapy in single nanoparticle. Upon modification with arginine-glycine-aspartic-cysteine acid (RGDC) peptide, PDA-RGDC can successfully target tumor site. Moreover, PDA-RGDC can load a chemotherapy drug, doxorubicin (DOX), whose release can be triggered by near-infrared (NIR) light and pH dual-stimuli. The in vitro and in vivo experiments show that this platform can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect. Our results offer a way to harness PDA-based theranostic agents to achieve PA imaging-guided cancer therapy. STATEMENT OF SIGNIFICANCE: NIR-light adsorbed nanoparticles combing the advantage of PAI and PTT (TNP-PAI/PTT) are expected to play a significant role in the dawning era of personalized medicine. However, the reported Au-, Ag-, Cu-, Co-, and other metal based, carbon-based TNP-PAI/PTT suffer from complex multicomponent system and poor biocompatibility and biodegradability. To overcome this limitation, biocompatible polydopamine nanoparticles (PDAs), structurally similar to naturally occurring melanin, were designed as both PA imaging contrast agent and a chemo-thermotherapy therapy agent for tumor. RGDC peptide modified PDAs can improve the PA imaging and PTT efficiency and specific targeted deliver doxorubicin (DOX) to perinuclear region of tumor cells. Our finding may help the development of PDA-based nanoplatform for PA imaging-directed synergistic therapy of tumor in clinic.

Achieving ultrasensitive in vivo detection of bone crack with polydopamine-capsulated surface-enhanced Raman nanoparticle.

The timely diagnosis and intervention of bone microdamage are essential for preventing its accumulation and further diminishing the risk of skeletal fracture. Although staining methods have been adopted to better depict the microdamage on bone, their clinical impacts are still limited because they are based on histological sections which are inherently destructive. Here, highly sensitive and non-invasive in vivo detection of bone crack can be achieved by surface-enhanced Raman scattering (SERS) technique using a carefully chosen polydopamine (PDA)-SERS nanoparticle tag. The bone crack can be specifically labeled by PDA-SERS tags taking advantage of high affinity of PDA towards calcium exposed on the damaged bone, and identified by an intense featured Raman signal both in vitro and in vivo benefiting from the surface-enhanced resonance Raman scattering effect. As a preliminary in vivo application, it is found that PDA-SERS tags present no serious adverse effect in mouse model and hold good biocompatibility. This work may help the development of SERS technique for ultrasensitive in vivo detection of bone crack in clinic.