Neutrophils in Cancer immunotherapy: friends or foes?

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

Observation of 3D acoustic quantum Hall states.

Quantum Hall effect, the quantized transport phenomenon of electrons under strong magnetic fields, remains one of the hottest research topics in condensed matter physics since its discovery in 2D electronic systems. Recently, as a great advance in the research of quantum Hall effects, the quantum Hall effect in 3D systems, despite its big challenge, has been achieved in the bulk ZrTe5 and Cd3As2 materials. Interestingly, Cd3As2 is a Weyl semimetal, and quantum Hall effect is hosted by the Fermi arc states on opposite surfaces via the Weyl nodes of the bulk, and induced by the unique edge states on the boundaries of the opposite surfaces. However, such intriguing edge state distribution has not yet been experimentally observed. Here, we aim to reveal experimentally the unusual edge states of Fermi arcs in acoustic Weyl system with the aid of pseudo-magnetic field. Benefiting from the macroscopic nature of acoustic crystals, the pseudo-magnetic field is introduced by elaborately designed the gradient on-site energy, and the edge states of Fermi arcs on the boundaries of the opposite surfaces are unambiguously demonstrated in experiments. Our system serves as an ideal and highly tunable platform to explore the Hall physics in 3D system, and has the potential in the application of new acoustic devices.

Meta-analysis of machine learning models for the diagnosis of central precocious puberty based on clinical, hormonal (laboratory) and imaging data.

Background: Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation test, which is expensive and time-consuming. With the widespread application of artificial intelligence in medicine, some studies have utilized clinical, hormonal (laboratory) and imaging data-based machine learning (ML) models to identify CPP. However, the results of these studies varied widely and were challenging to directly compare, mainly due to diverse ML methods. Therefore, the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for CPP remains elusive. The aim of this study was to investigate the diagnostic value of ML models based on clinical, hormonal (laboratory) and imaging data for CPP through a meta-analysis of existing studies. Methods: We conducted a comprehensive search for relevant English articles on clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP, covering the period from the database creation date to December 2023. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP. The I2 test was employed to evaluate heterogeneity, and the source of heterogeneity was investigated through meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. Results: Six studies met the eligibility criteria. The pooled sensitivity and specificity were 0.82 (95% confidence interval (CI) 0.62-0.93) and 0.85 (95% CI 0.80-0.90), respectively. The LR+ was 6.00, and the LR- was 0.21, indicating that clinical, hormonal (laboratory) and imaging data-based ML models exhibited an excellent ability to confirm or exclude CPP. Additionally, the SROC curve showed that the AUC of the clinical, hormonal (laboratory) and imaging data-based ML models in the diagnosis of CPP was 0.90 (95% CI 0.87-0.92), demonstrating good diagnostic value for CPP. Conclusion: Based on the outcomes of our meta-analysis, clinical and imaging data-based ML models are excellent diagnostic tools with high sensitivity, specificity, and AUC in the diagnosis of CPP. Despite the geographical limitations of the study findings, future research endeavors will strive to address these issues to enhance their applicability and reliability, providing more precise guidance for the differentiation and treatment of CPP.

Valley edge states as bound states in the continuum.

Bound states in the continuum (BICs) are spatially localized states with energy embedded in the continuum spectrum of extended states. The combination of BICs physics and nontrivial band topology theory givs rise to topological BICs, which are robust against disorders and meanwhile, the merit of conventional BICs is attracting wide attention recently. Here, we report valley edge states as topological BICs, which appear at the domain wall between two distinct valley topological phases. The robustness of such BICs is demonstrated. The simulations and experiments show great agreement. Our findings of valley related topological BICs shed light on both BICs and valley physics, and may foster innovative applications of topological acoustic devices.

Wood-converted porous carbon decorated with MIL-101(Fe) derivatives for promoting photo-Fenton degradation of ciprofloxacin.

In response to the escalating concerns over antibiotics in aquatic environments, the photo-Fenton reaction has been spotlighted as a promising approach to address this issue. Herein, a novel heterogeneous photo-Fenton catalyst (Fe3O4/WPC) with magnetic recyclability was synthesized through a facile two-step process that included in situ growth and subsequent carbonization treatment. This catalyst was utilized to expedite the photocatalytic decomposition of ciprofloxacin (CIP) assisted by H2O2. Characterization results indicated the successful anchoring of MIL-101(Fe)-derived spindle-like Fe3O4 particles in the multi-channeled wood-converted porous carbon (WPC) scaffold. The as-synthesized hybrid photocatalysts, boasting a substantial specific surface area of 414.90 m2·g-1 and an excellent photocurrent density of 0.79 µA·cm-2, demonstrated superior photo-Fenton activity, accomplishing approximately 100% degradation of CIP within 120 min of ultraviolet-light exposure. This can be attributed to the existence of a heterojunction between Fe3O4 and WPC substrate that promotes the migration and enhances the efficient separation of photogenerated electron-hole pairs. Meanwhile, the Fe(III)/Fe(II) redox circulation and mesoporous wood carbon in the catalyst synergistically enhance the utilization of H2O and accelerate the formation of •OH radicals, leading to heightened degradation efficiency of CIP. Experiments utilizing chemical trapping techniques have demonstrated that •OH radicals are instrumental in the CIP degradation process. Furthermore, the study on reusability indicated that the efficiency in removing CIP remained at 89.5% even through five successive cycles, indicating the structural stability and excellent recyclability of Fe3O4/WPC. This research presented a novel pathway for designing magnetically reusable MOFs/wood-derived composites as photo-Fenton catalysts for actual wastewater treatment.

Inflammatory cytokines and risk of allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Epidemiological and experimental evidences have implicated chronic inflammation in the association with allergic rhinitis (AR). However, it remains unclear whether specific circulating cytokines are the cause of AR or the consequence of bias. To examine whether genetic-predicted changes in circulating cytokine concentrations are related to the occurrence of AR, we conducted a two-sample Mendelian randomization (MR) analysis. METHODS: We investigated the causal effects of 26 circulating inflammatory cytokines on AR through MR analysis. The primary method employed in this study was the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted using simple median, weighted median, penalized weighted median, and MR-Egger regression. RESULTS: Our study revealed suggestive evidence that higher levels of circulating IL-18 (OR per one standard deviation [SD] increase: 1.006; 95 % CI, 1.002 to 1.011; P = 0.006, PFDR = 0.067, random-effects IVW method) and Macrophage inflammatory protein-1α (MIP-1α) (OR per one SD increase: 1.015; 95 % CI, 1.004 to 1.026; P = 0.009, PFDR = 0.048, random-effects IVW method) were associated with an increased risk of AR. Conversely, higher levels of circulating TRAIL were associated with a decreased risk of AR (OR per one SD increase: 0.993; 95 % CI, 0.989 to 0.997; P = 4.58E-4, PFDR = 0.004, random-effects IVW method). Only the results of TRAIL exist after Bonferroni-correction (the p-value < 0.0019). Sensitivity analysis yielded directionally consistent results. No significant associations were observed between other circulating inflammatory cytokines and AR. CONCLUSION: Genetically predicted levels of IL-18, and MIP-1α are likely to associated with an increased risk of AR occurrence. Genetically predicted levels of TRAIL are statistically significant in reducing the risk of AR occurrence. However, the current research evidence does not support an impact of other inflammatory cytokines on the risk of AR. Future studies are needed to provide additional evidence to support the current conclusions.

Observation of Higher-Order Nodal-Line Semimetal in Phononic Crystals.

Higher-order topological insulators and semimetals, which generalize the conventional bulk-boundary correspondence, have attracted extensive research interest. Among them, higher-order Weyl semimetals feature twofold linear crossing points in three-dimensional momentum space, 2D Fermi-arc surface states, and 1D hinge states. Higher-order nodal-point semimetals possessing Weyl points or Dirac points have been implemented. However, higher-order nodal-line or nodal-surface semimetals remain to be further explored in experiments in spite of many previous theoretical efforts. In this work, we realize a second-order nodal-line semimetal in 3D phononic crystals. The bulk nodal lines, 2D drumhead surface states guaranteed by Zak phases, and 1D flat hinge states attributed to k_{z}-dependent quadrupole moments are observed in simulations and experiments. Our findings of nondispersive surface and hinge states may promote applications in acoustic sensing and energy harvesting.

3D hierarchic interfacial assembly of Au nanocage@Au along with IS-AgMNPs for simultaneous, ultrasensitive, reliable, and quantitative SERS detection of colorectal cancer related miRNAs.

Simultaneous, reliable, and ultra-sensitive analysis of promising miRNA biomarkers of colorectal cancer (CRC) in serum is critical for early diagnosis and prognosis of CRC. In this work, we proposed a novel 3D hierarchic assembly clusters-based SERS strategy with dual enrichment and enhancement designed for the ultrasensitive and quantitative analysis of two upregulated CRC-related miRNAs (miR-21 and miR-31). The biosensor contains the following: (1) SERS probe, Au nanocage@Au nanoparticles (AuNC@Au NPs) labeled with Raman reporters (RaRs). (2) magnetic capture unit, Ag-coated Fe3O4 magnetic nanoparticles (AgMNPs) modified with internal standard (IS). (3) signal amplify probes (SA probes) for the formation of hierarchic assembly clusters. Based on this sensing strategy, the intensity ratio IRaRs/IIS with Lg miRNAs presents a wide linear range (10 aM-100 pM) with a limit of detection of 3.46 aM for miR-21, 6.49 aM for miR-31, respectively. Moreover, the biosensor shows good specificity and anti-interference ability, and the reliability and repeatability of the strategy were then verified by practical detection of clinical serum. Finally, the biosensor can distinguish CRC cancer subjects from normal ones and guide the distinct tumor, lymph node, and metastasis (TNM) stages. Overall, benefiting from the face-to-face coupling of hierarchic assembly clusters, rapid magnetic enrichment and IS signal calibration of AgMNPs, the established biosensor achieves ultra-sensitive and simultaneous detection of dual miRNAs and opens potential avenues for prediction and staging of CRC.

Non-Hermitian Topological Phononic Metamaterials.

Non-Hermitian (NH) physics describes novel phenomena in open systems that allow generally complex spectra. Introducing NH physics into topological metamaterials, which permits explorations of topological wave phenomena in artificially designed structures, not only enables the experimental verification of exotic NH phenomena in these flexible platforms, but also enriches the manipulation of wave propagation beyond the Hermitian cases. Here, a perspective on the advances in the research of NH topological phononic metamaterials is presented, which covers the exceptional points and their topological geometries, the skin effect related to the topology of complex spectra, the interplay of NH effects and topological states in phononic metamaterials, etc.

In Situ Tyrosinase Monitoring by Wearable Microneedle Patch toward Clinical Melanoma Screening.

Despite the potential indicating role of tyrosinase (TYR) in cutaneous melanoma, how to capture the real changes of TYR in suspicious skin remains a major challenge. Unlike the traditional human serum test, this study reports a sensing platform that incorporates a wearable microneedle (MN) patch and trimetallic Au@Ag-Pt nanoparticles (NPs) for surface-enhanced Raman scattering (SERS) and colorimetric dual-mode detecting TYR in human skin in situ toward potential melanoma screening. In the presence of TYR, catechol immobilized on MN is preferentially oxidized to benzoquinone, which competitively impedes the interaction of MN and Au@Ag-Pt NPs, triggering the SERS-colorimetric signal reciprocal switch. Using a B16F10 mouse melanoma model, our platform is capable of noninvasively piercing the skin surface and detecting TYR levels before and during anti-PD-1 antibody treatment, which would be highly informative for prognostic judgment and illness monitoring of melanoma. Through in situ sensing for capturing the metabolic changes of TYR in advance, this platform was successfully applied to discriminate the melanoma subjects from skin moles and normal ones (p < 0.001), as well as screen potential melanoma from lactate dehydrogenase (LDH)-negative patients. Melanoma growth and prognosis can still be monitored through recording the continuous change of TYR levels. More importantly, the well-defined flexible and stretchable characteristics of the MN patch allow robustly adhering to the skin without inducing chemical or physical irritation. We believe this platform integrating MN-based in situ sensing, TYR responsiveness, and SERS/colorimetric dual-readout strategy will have high clinical importance in early diagnosis and monitoring of cutaneous melanoma.

Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings.

Erratum: Author correction to 'Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy' [Acta Pharm Sin B 13 (2023) 1303-1317].

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

Topological phononic metamaterials.

The concept of topological energy bands and their manifestations have been demonstrated in condensed matter systems as a fantastic paradigm toward unprecedented physical phenomena and properties that are robust against disorders. Recent years, this paradigm was extended to phononic metamaterials (including mechanical and acoustic metamaterials), giving rise to the discovery of remarkable phenomena that were not observed elsewhere thanks to the extraordinary controllability and tunability of phononic metamaterials as well as versatile measuring techniques. These phenomena include, but not limited to, topological negative refraction, topological 'sasers' (i.e. the phononic analog of lasers), higher-order topological insulating states, non-Abelian topological phases, higher-order Weyl semimetal phases, Majorana-like modes in Dirac vortex structures and fragile topological phases with spectral flows. Here we review the developments in the field of topological phononic metamaterials from both theoretical and experimental perspectives with emphasis on the underlying physics principles. To give a broad view of topological phononics, we also discuss the synergy with non-Hermitian effects and cover topics including synthetic dimensions, artificial gauge fields, Floquet topological acoustics, bulk topological transport, topological pumping, and topological active matters as well as potential applications, materials fabrications and measurements of topological phononic metamaterials. Finally, we discuss the challenges, opportunities and future developments in this intriguing field and its potential impact on physics and materials science.

Urchin-Shaped Au-Ag@Pt Sensor Integrated Lateral Flow Immunoassay for Multimodal Detection and Specific Discrimination of Clinical Multiple Bacterial Infections.

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au-Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus (S. aureus) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood samples (E. coli, S. aureus, and P. aeruginosa) effectively according to specific bacterial Raman "fingerprints" by partial least-squares-discriminant analysis (PLS-DA). More importantly, this LFIA was successfully applied to blood samples with satisfactory recoveries from 90.3% to 108.8% and capable of identifying the infected patients (N = 4) from healthy subjects (N = 2) with great accuracy. Overall, the multimodal LFIA incorporates bacteria discrimination and quantitative detection, offering an avenue for early warning and diagnosis of bacterial infection.

Observation of geometry-dependent skin effect in non-Hermitian phononic crystals with exceptional points.

Exceptional points and skin effect, as the two distinct hallmark features unique to the non-Hermitian physics, have each attracted enormous interests. Recent theoretical works reveal that the topologically nontrivial exceptional points can guarantee the non-Hermitian skin effect, which is geometry-dependent, relating these two unique phenomena. However, such novel relation remains to be confirmed by experiments. Here, we realize a non-Hermitian phononic crystal with exceptional points, which exhibits the geometry-dependent skin effect. The exceptional points connected by the bulk Fermi arcs, and the skin effects with the geometry dependence, are evidenced in simulations and experiments. Our work, building an experimental bridge between the exceptional points and skin effect and uncovering the unconventional geometry-dependent skin effect, expands a horizon in non-Hermitian physics.

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).

Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus. Notably, most of the PIKK inhibitors (such as VX-970 and M3814) related to DNA damage response have also shown good efficacy in clinical trials. However, these drugs still require a suitable combination therapy to overcome drug resistance or improve antitumor activity. Based on the aforementioned facts, we summarised the efficacy of PIKK, PI3K, and AKT inhibitors in the therapy of human malignancies and the resistance mechanisms of targeted therapy, in order to provide deeper insights into cancer treatment.

Antichirality Emergent in Type-II Weyl Phononic Crystals.

Chiral anomaly as the hallmark feature lies in the heart of the researches for Weyl semimetal. It is rooted in the zeroth Landau level of the system with an applied magnetic field. Chirality or antichirality characterizes the propagation property of the one-way zeroth Landau level mode, and antichirality means an opposite group velocity compared to the case of chirality. Chirality is commonly observed for Weyl semimetals. Interestingly, the type-II Weyl point, with the overtilted dispersion, may flip the chirality to the antichirality, which, however, is yet to be evidenced despite numerous previous experimental efforts. Here, we implement the type-II Weyl point in sonic crystals, and by creating the pseudomagnetic fields with geometric deformation, the chirality flip of zeroth Landau levels is unambiguously demonstrated. Our Letter unveils the novel antichiral transport in the presence of time-reversal symmetry, and paves the way toward the state-of-the-art manipulation of sound waves.

Topological materials for full-vector elastic waves.

Elastic wave manipulation is important in a wide variety of applications, including information processing in small elastic devices and noise control in large solid structures. The recent emergence of topological materials has opened new avenues for modulating elastic waves in solids. However, because of the full-vector feature and the complicated couplings of the longitudinal and transverse components of elastic waves, manipulating elastic waves is generally difficult compared with manipulating acoustic waves (scalar waves) and electromagnetic waves (vectorial waves but transverse only). To date, topological materials, including insulators and semimetals, have been used for acoustic and electromagnetic waves. Although topological materials with elastic waves have also been reported, the observed topological edge modes lie on the domain wall. A natural question arises: Is there an elastic metamaterial with topological edge modes on its own boundary? Here, we report a 3D metal-printed bilayer metamaterial that topologically insulates elastic waves. By introducing chiral interlayer couplings, the spin-orbit couplings for elastic waves are induced, which give rise to nontrivial topological properties. Helical edge states with vortex features were demonstrated on the boundary of the single topological phase. We further show a heterostructure of the metamaterial that exhibits tunable edge transport. Our findings could be used in devices based on elastic waves in solids.

Targeting the TNF-α-TNFR interaction with EGCG to block NF-κB signaling in human synovial fibroblasts.

The tumor necrosis factor alpha (TNF-α)-TNF-α receptor (TNFR) interaction plays a central role in the pathogenesis of various autoimmune diseases, particularly rheumatoid arthritis, and is therefore considered a key target for drug discovery. However, natural compounds that can specifically block the TNF-α-TNFR interaction are rarely reported. (-)-Epigallocatechin-3-gallate (EGCG) is the most active, abundant, and thoroughly investigated polyphenolic compound in green tea. However, the molecular mechanism by which EGCG ameliorates autoimmune arthritis remains to be elucidated. In the present study, we found that EGCG can directly bind to TNF-α, TNFR1, and TNFR2 with similar µM affinity and disrupt the interactions between TNF-α and TNFR1 and TNFR2, which inhibits TNF-α-induced L929 cell death, blocks TNF-α-induced NF-κB activation in 293-TNF-α response cell line, and eventually leads to inhibition of TNF-α-induced NF-κB signaling pathway in HFLS and MH7A cells. Thus, regular consumption of EGCG in green tea may represent a potential therapeutic agent for the treatment of TNF-α-associated diseases.

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.