Two new aromatic tenvermectins from mutant Streptomyces avermitilis HU02-06.

Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.

Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.

Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release.

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.

Digital Circulating Tumor Cells Quantification.

Circulating tumor cells (CTCs) are an emerging but vital biomarker for cancer management. An efficient methodology for accurately quantifying CTCs remains challenging due to their rareness. Here, we develop a digital CTC detection strategy using partitioning instead of enrichment to quantify CTCs. By utilizing the characteristics of droplet microfluidics that can rapidly generate a large number of parallel independent reactors, combined with Poisson distribution, we realize the quantification of CTCs in the blood directly. The limit of detection of our digital CTCs quantification assay is five cells per 5 mL of whole blood. By simultaneously detecting multiple genetic mutations, our approach achieves highly sensitive and specific detection of CTCs in peripheral blood from NSCLC patients (AUC = 1). Our digital platform offers a potential approach and strategy for the quantification of CTCs, which could contribute to the advancement of cancer medical management.

Electrochemical Monitoring of Sphingosine-1-phosphate-Induced ATP Release Using a Microsensor Based on an Entropy-Driven Bipedal DNA Walker.

Neuropathic pain is a chronic and severe syndrome for which effective therapy is insufficient and the release of ATP from microglia induced by sphingosine-1-phosphate (S1P) plays a vital role in neuropathic pain. Therefore, there is an urgent demand to develop highly sensitive and selective ATP biosensors for quantitative monitoring of low-concentration ATP in the complex nervous system, which helps in understanding the mechanism involved in neuropathic pain. Herein, we developed an electrochemical microsensor based on an entropy-driven bipedal DNA walker. First, the microsensor specifically recognized ATP via ATP aptamers, initiating the entropy-driven bipedal DNA walker. Subsequently, the bipedal DNA walker autonomously traversed the microelectrode interface, introducing methylene blue to the electrode surface and achieving cascade signal amplification. This microsensor showed excellent selectivity, stability, and a low limit of detection at 1.13 nM. The S1P-induced ATP release from BV2 cells was successfully monitored, and it was observed that dicumarol could inhibit this release, suggesting dicumarol as a potential treatment for neuropathic pain. The microsensor's small size exhibited significant potential for monitoring ATP level changes in neuropathic pain in vivo, which provides a new strategy for in situ and quantitative monitoring of nonelectroactive biomolecules associated with neurological diseases.

Erianin promotes apoptosis and inhibits Akt-mediated aerobic glycolysis of cancer cells.

Highly activated aerobic glycolysis provides the metabolic requirements for tumor cell growth and proliferation. Erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has been reported to exert antitumor activity in multiple cancers. However, whether Erianin exerts inhibitory effects on aerobic glycolysis and the inherent mechanism remain poorly defined in non-small cell lung cancer (NSCLC). Here, we showed that Erianin inhibited the cell viability and proliferation, and induced apoptosis in NSCLC cells. Moreover, Erianin overtly suppressed aerobic glycolysis via decreasing HK2 expression. Mechanistically, Erianin dose-dependently curbed the Akt-GSK3ß signaling pathway phosphorylation activation, which afterwards downregulated HK2 expression. Meanwhile, Erianin inhibited HCC827 tumor growth in vivo. Taken together, our results suggest that the natural product Erianin can suppress aerobic glycolysis and exert potent anticancer effects via the Akt-GSK3ß signaling pathway in NSCLC cells.

A photoelectrochemical cytosensor based on a Bi2S3-MoS2 heterojunction-modified reduced oxide graphene honeycomb film for sensitive detection of circulating tumor cells.

A novel photoelectrochemical (PEC) cytosensor for the ultrasensitive detection of circulating tumor cells (CTCs) was developed. The bio-inspired reduced graphene oxide (rGO) honeycomb film photoelectrode was fabricated via a "breath figure" method, followed by the self-assembly of a Bi2S3-MoS2 heterojunction. The resulting Bi2S3-MoS2 heterojunction-modified rGO honeycomb film was employed as a sensing matrix for the first time. Compared to the smooth rGO film, the significant enhanced photocurrent of the photoelectrode under visible light was attributed to its improved visible light absorption, increased surface area and enhanced separation efficiency of photo-generated electron-hole pairs, which met the requirements of the PEC sensor for detecting larger targets. By virtue of the photocurrent decrease due to the steric hindrance of MCF-7 cells, which were captured by an aptamer immobilized on the surface of the photoelectrode, a cytosensor for detecting CTCs was achieved, showing a wide linear range of 10-1 × 105 cells per mL and a low detection limit of 2 cells per mL. Furthermore, MCF-7 cells in human serum were determined by this PEC biosensor, exhibiting great potential in the clinical detection of CTCs.

Multilayer nanodrug delivery system with spatiotemporal drug release improves tumor microenvironment for synergistic anticancer therapy.

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Nanoparticles loaded withß-Lapachone and Fe3+exhibit enhanced chemodynamic therapy by producing H2O2through cascaded amplification.

The rapid, irreversible change of active Fe2+to inactive Fe3+after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here,ß-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated asß-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.

Development of fecal microbial diagnostic marker sets of colorectal cancer using natural language processing method.

BACKGROUND: Cancer screening and early detection greatly increase the chances of successful treatment. However, most cancer types lack effective early screening biomarkers. In recent years, natural language processing (NLP)-based text-mining methods have proven effective in searching the scientific literature and identifying promising associations between potential biomarkers and disease, but unfortunately few are widely used. METHODS: In this study, we used an NLP-enabled text-mining system, MarkerGenie, to identify potential stool bacterial markers for early detection and screening of colorectal cancer. After filtering markers based on text-mining results, we validated bacterial markers using multiplex digital droplet polymerase chain reaction (ddPCR). Classifiers were built based on ddPCR results, and sensitivity, specificity, and area under the curve (AUC) were used to evaluate the performance. RESULTS: A total of 7 of the 14 bacterial markers showed significantly increased abundance in the stools of colorectal cancer patients. A five-bacteria classifier for colorectal cancer diagnosis was built, and achieved an AUC of 0.852, with a sensitivity of 0.692 and specificity of 0.935. When combined with the fecal immunochemical test (FIT), our classifier achieved an AUC of 0.959 and increased the sensitivity of FIT (0.929 vs. 0.872) at a specificity of 0.900. CONCLUSIONS: Our study provides a valuable case example of the use of NLP-based marker mining for biomarker identification.

Non-interference delivery of Ce6 and DOX in NIR light-responsive liposomes for synergetic cervical cancer therapy.

Multi-model combination treatment of malignant tumors can make up for the shortcomings of single treatment through multi-target and multi-path to achieve more ideal tumor treatment effect. However, the mutual interference of different drugs in the delivery processin vivoand the difficulty of effective drug accumulation in tumor cells are the bottlenecks of combined therapy. To this project, light-responsive liposomes loading doxorubicin (DOX) and chlorin e6 (Ce6) (DOX-Ce6-Lip) without mutual interference were engineered by thin film hydration method. This kind of nano-drug delivery system increased the drugs concentration accumulated in tumor sites through enhanced permeability and retention effect, and reduced the toxic and side effects of drugs on normal tissuesin vivo. In addition, after entering the tumor cells, Ce6 produced a large number of reactive oxygen species under 660 nm NIR laser irradiation, which further oxidized the unsaturated fatty acid chain in the liposomes and caused the collapse of the liposomes, thus realizing the stimulus-responsive release of Ce6 and DOX. The concentrations of DOX and Ce6 in the tumor cells rapidly reached the peak and achieved a more effective combination of chemotherapy and photodynamic therapy (PDT). Consequently, DOX-Ce6-Lip followed by 660 nm NIR irradiation achieved an efficient tumor growth inhibition of 71.90 ± 3.14%, indicating the versatile potential of chemotherapy and PDT. In conclusion, this study provides a delivery scheme for drugs with different solubilities and an effectively combined anti-tumor therapy method.

Postoperative circulating tumor DNA detection and CBLB mutations are prognostic biomarkers for gastric cancer.

BACKGROUND: Several studies have demonstrated that circulating tumor DNA (ctDNA) can be used to predict the postoperative recurrence of several cancers. However, there are few studies on the use of ctDNA as a prognosis tool for gastric cancer (GC) patients. OBJECTIVE: This study aims to determine whether ctDNA could be used as a prognostic biomarker in GC patients through multigene-panel sequencing. METHODS: Using next-generation sequencing (NGS) Multigene Panels, the mutational signatures associated with the prognosis of GC patients were identified. We calculated the survival probability with Kaplan-Meier and used the Log-rank test to compare survival curves between ctDNA-positive and ctDNA-negative groups. Potential application of radiology combined with tumor plasma biomarker analysis of ctDNA in GC patients was carried out. RESULTS: Disease progression is more likely in ctDNA-positive patients as characterized clinically by a generally higher T stage and a poorer therapeutic response (P < 0.05). ctDNA-positive patients also had worse overall-survival (OS: P = 0.203) and progression-free survival (PFS: P = 0.037). The combined analysis of ctDNA, radiological, and serum biomarkers in four patients indicated that ctDNA monitoring can be a good complement to radiological and plasma tumor markers for GC patients. Kaplan-Meier analysis using a cohort of GC patients in the TCGA database showed that patients with CBLB mutations had shorter OS and PFS than wild-type patients (OS: P = 0.0036; PFS: P = 0.0027). CONCLUSIONS: This study confirmed the utility and feasibility of ctDNA in the prognosis monitoring of gastric cancer.

Ultrasensitive electrochemical biosensor for detection of circulating tumor cells based on a highly efficient enzymatic cascade reaction.

There has been great interest in the enzymatic cascade amplification strategy for the electrochemical detection of circulating tumor cells (CTCs). In this work, we designed a highly efficient enzymatic cascade reaction based on a multiwalled carbon nanotubes-chitosan (MWCNTs-CS) composite for detection of CTCs. A high electrochemical effective surface area was obtained for a MWCNTs-CS-modified glassy carbon electrode (GCE) for loading glucose oxidase (GOD), as well as a high loading rate and high electrical activity of the enzyme. As a 'power source', the MWCNTs-CS composites provided a strong driving power for horseradish peroxidase (HRP) on the surface of polystyrene (PS) microspheres, which acted as probes for capturing CTCs and allowed the reaction to proceed with further facilitation of electron transfer. Aptamer, CTCs, and PS microspheres with HRP and anti-epithelial cell adhesion molecule (anti-EpCAM) antibody were assembled on the MWCNTs-CS/GCE to allow for the modulation of enzyme distance at the micrometer level, and thus ultra-long-range signal transmission was made possible. An ultrasensitive response to CTCs was obtained via this proposed sensing strategy, with a linear range from 10 cell mL-1 to 6 × 106 cell mL-1 and a detection limit of 3 cell mL-1. Moreover, this electrochemical sensor possessed the capability to detect CTCs in serum samples with satisfactory accuracy, which indicated great potential for early diagnosis and clinical analysis of cancer.

CdSe@CdS quantum dot-sensitized Au/α-Fe2O3 structure for photoelectrochemical detection of circulating tumor cells.

Circulating tumor cells (CTCs) are the important biomarker for cancer diagnosis and individualized treatment. However, due to the extreme rarity of CTCs (only 1-10 CTCs are found in every milliliter of peripheral blood) high sensitivity and selectivity are urgently needed for CTC detection. Here, a sandwich PEC cytosensor for the ultrasensitive detection of CTCs was developed using the photoactive material Au NP/-Fe2O3 and core-shell CdSe@CdS QD sensitizer. In the proposed  protocol, the CdSe@CdS QD/Au NP/α-Fe2O3-sensitized structure with cascade band-edge levels could evidently promote the photoelectric conversion efficiency due to suitable light absorption and efficient electron-hole pair recombination inhibition. Additionally, a dendritic aptamer-DNA concatemer was constructed for highly efficient capture of MCF-7 cells carrying CdSe@CdS QDs, a sensitive material. The linear range of this proposed signal-on PEC sensing method was 300 cell mL-1 to 6 × 105 cell mL-1 with a detection limit of 3 cell mL-1, and it demonstrated an ultrasensitive response to CTCs. Furthermore, this PEC sensor enabled accurate detection of  CTCs in serum samples. Hence, a promising strategy for CTC detection in clinical diagnosis was developed based on CdSe@CdS QD-sensitized Au NP/α-Fe2O3-based PEC cytosensor with dendritic aptamer-DNA concatemer.

Standardization of organoid culture in cancer research.

Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self-assembled three-dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high-throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient-derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling.

Capture and release of circulating tumor cells stimulated by pH and NIR irradiation of magnetic Fe3O4@ZIF-8 nanoparticles.

Detecting and analyzing circulating tumor cells(CTCs) is significant for early diagnosis, management, and personalized treatment of tumors. Herein, a smart magnetic aptamer modified Fe3O4@ZIF-8 core/shell structured nanoparticle (NPs) was successfully constructed using for capture and simultaneous pH- and NIR-irradiation responsive release of CTCs. Taking MCF-7 as model CTCs, it could be captured ca. 60 % in low-concentration artificial blood by aptamer (SYL3C) on the surface of Fe3O4@ZIF-8 NPs. After magnetic separation, the ZIF-8 shell in aptamer-modified Fe3O4@ZIF-8 NPs carrying captured CTCs would disintegrate within 20 min under the synergistic effect of an acidic environment (pH=6.0) and NIR irradiation leading to the release of CTCs with high cell viability, which was benefited for the subsequent culture and analysis. This magnetic and core/shell structured device integrated high-efficiency capture, quick isolation and perfect release into one system, which showed great potentials for the detection of CTCs in the clinic.

Safety and efficacy analysis of chemoradiotherapy/radiotherapy combined with nimotuzumab for treating unresectable oesophageal squamous cell carcinoma in elderly patients: a retrospective analysis.

OBJECTIVE: To investigate the safety and efficacy of chemoradiotherapy or radiotherapy combined with nimotuzumab in the treatment of unresectable oesophageal squamous cell carcinoma (ESCC) in elderly patients. METHODS: This study retrospectively analysed 54 cases of elderly patients (aged over 70 years) with unresectable ESCC in our centre between December 2016 and November 2019. The patients were treated with a radiation dose of 50-61.6 Gy (25-30 fractions) combined with nimotuzumab for targeted therapy with or without chemotherapy according to each patient's condition. The patients were observed for quality of life, safety, side effects and survival before and after the treatment. RESULTS: Among the 54 patients, 26 were treated with nimotuzumab combined with chemoradiotherapy and 28 were treated with nimotuzumab combined with radiotherapy. Toxicities were mainly oesophagitis (≥ Grade 2, 38.9%), myelosuppression (≥ Grade 3, 24.1%) and hypoproteinaemia (any grade, 94.4%). The rates of complete response, partial response, disease stability and disease progression were 11.1% (6/54), 81.5% (44/54), 3.7% (2/54) and 3.7% (2/54), respectively, and the overall objective response rate was 92.6% (50/54). The median follow-up time was 35.1 months, and the 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 61.1% (1 year OS) and 35.2% (2 year OS), 42.6% (1 year PFS) and 16.7% (2 year PFS), respectively. The median OS and PFS rates were 16.0 and 10.0 months, respectively. CONCLUSION: Nimotuzumab combined with chemoradiotherapy or radiotherapy was well tolerated in elderly patients with unresectable ESCC. This combination can achieve a good treatment response and enhance survival.

Rapid In Situ Hydrogel LAMP for On-Site Large-Scale Parallel Single-Cell HPV Detection.

Rapid human papillomavirus (HPV) screening is urgently needed for preventing and early diagnosis of cervical cancer in rural areas. To date, no HPV nucleic acid test (NAT) can be implemented within a single patient visit starting from clinical samples. Here, we develop a hydrogel loop-mediated isothermal amplification (LAMP) method in a fashion of large-scale parallel (about 1000 cells) in situ HPV DNA detection in clinical cervical exfoliated cells at the single-cell level. It can be used with a hotplate and smartphone to obtain HPV NAT results in less than 30 min, which is especially suitable for the on-site scenario. We apply this rapid HPV NAT on 40 clinical cervical exfoliated cell samples and compare the results to a clinical gold standard quantitative polymerase chain reaction (qPCR) method [area under curve (AUC), 1.00]. Meanwhile, our assay can provide HPV infection information for large-scale parallel single clinical cervical exfoliated cells, which cannot be received from traditional NAT methods. Our findings suggest the potential of in situ hydrogel LAMP as a powerful tool for clinical HPV screening and fundamental research.

Construction of multifunctional carboxymethyl cellulose nanohydrogel carriers based on near-infrared DNA-templated quantum dots for tumor theranostics.

Multifunctional therapeutic platforms with targeted delivery, fast diagnosis, and efficient therapy could effectively reduce side effects and improve treatment in the clinical therapy of tumors. Near-infrared DNA-templated CdTeSe quantum dots (DNA-CdTeSe QDs) were developed as building blocks to construct a multifunctional carboxymethyl cellulose (CMC)-based nanohydrogel as a nanocarrier to address the challenges of serious side effects and precise treatment in cancer theranostics, including active tumor targeting, fluorescence tracking, controlled drug release, chemotherapy and gene regulation. Single-stranded DNA containing the complementarity sequence of miRNA and cystine, as co-crosslinkers, initiated hybridization between the DNA-CdTeSe QD-modified CMC chain with the anti-nucleolin aptamer DNA (AS1411)-modified CMC chain to form the hydrogels. DOX, as a model drug, was successfully incorporated into the hydrogels. The synthesized multifunctional hydrogel nanocarriers with an average diameter of 150 nm could be taken up through targeting and achieved the controlled release of DOX by triggering both glutathione (GSH) and miRNA in the tumor microenvironment. The CdTeSe QDs trapped in nanohydrogels acted as fluorophores for bioimaging in the diagnosis and treatment process. The proposed multifunctional delivery system provided a potential platform for tumor imaging and precise therapy.

MoS2 nanoflower-mediated enhanced intratumoral penetration and piezoelectric catalytic therapy.

The absence of lymphatic vessels in tumors leads to the retention of interstitial fluid, and the formation of an inverse pressure difference between the tumor and blood vessels hinders drug delivery deep into the tumor, which leads to tumor recurrence and metastasis. Therefore, we designed a novel strategy to downregulate tumor interstitial fluid pressure (TIFP) by water splitting in the tumor interstitium based on piezoelectric catalysis nanomedicine. First, the chemotherapeutic drug doxorubicin (DOX) was loaded on the piezoelectric catalytic material MoS2 and then encapsulated with tumor cell membrane (CM) to obtain MD@C. MD@C could not only target the tumor through homologous targeting but, more importantly, also triggered piezoelectric catalytic water splitting under ultrasound (US) stimulation; as a result, the TIFPs of U14 and PAN02 tumor-bearing mice were reduced to 57.14% and 45.5%, respectively, and the tumor inhibition rates of MD@C were 96.75% and 99.21%, which increased the perfusion of blood-derived drugs in the tumors. Moreover, the hydroxyl radicals generated by piezoelectric catalysis could effectively inhibit the growth of tumors in combination with DOX. Consequently, the piezoelectric catalytic water splitting strategy of MD@C can enhance drug delivery, providing a new universal platform for the treatment of solid malignant tumors.