Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

Transcriptome and functional analyses of phenotypic plasticity in sea grape Caulerpa okamurae.

Caulerpa is a marine green macroalga distinguished by a large single cell with multiple nuclei. It also exhibits remarkable morphological intraspecies variations, in response to diverse environmental types. However, the molecular mechanisms underlying this phenotypic plasticity remain poorly understood. In this work, we compare the transcriptomes of Caulerpa okamurae Weber Bosse, 1897 displaying altered phenotypes of cultivation and natural phenotypes and investigate significantly regulated genes and their biological functions using differential expression analyses. We observe light-harvesting complex upregulation and cellular framework stability downregulation in altered phenotypes compared to the natural phenotypes. Intertidal macrophytes reduce light capture to avoid photodamage and regulate their morphology to protect against wave damage. In contrast, the lower light conditions and the cultivation environment augment light capture and increase a morphology prioritizing light trapping. Moreover, the addition of simulated wave-sweeping stimuli induces a return to the natural morphology under high-light conditions, showing how mechanical stress affects morphological organization in C. okamurae. We provide detailed gene expression patterns in C. okamurae under varying light intensities and water conditions, suggesting a distinct influence on its morphological traits.

Development of a communication platform for patients with head and neck cancer for effective information delivery and improvement of doctor-patient relationship: application of treatment journey-based service blueprint.

BACKGROUND: Effective communication and information delivery enhance doctor-patient relationships, improves adherence to treatment, reduces work burden, and supports decision-making. The study developed a head and neck cancer (HNC) communication platform to support effective delivery of information about HNC treatment and improve the doctor-patient relationship. METHODS: This study was structured in three main phases: 1) The requirement elicitation phase sought an understanding of the HNC treatment journey and service failure points (FPs) obtained through patient/medical staff interviews and observations, along with a review of the electronic health record system; 2) The development phase involved core needs analysis, solutions development through a co-creation workshop, and validation of the solutions through focus groups; and 3) the proposed HNC communication platform was integrated with the current treatment system, and the flow and mechanism of the interacting services were structured using a service blueprint (SB). RESULTS: Twenty-two service FPs identified through interviews and observations were consolidated into four core needs, and solutions were proposed to address each need: an HNC treatment journey map, cancer survivor stories, operation consent redesign with surgical illustrations, and a non-verbal communication toolkit. The communication platform was designed through the SB in terms of the stage at which the solution was applied and the actions and interactions of the service providers. CONCLUSIONS: The developed platform has practical significance, reflecting a tangible service improvement for both patients and medical staff, making it applicable in hospital settings.

Thermal Equation of State of Cubic Silicon Carbide at High Pressures.

We have performed in situ X-ray diffraction measurements of cubic silicon carbide (SiC) with a zinc-blende crystal structure (B3) at high pressures and temperatures using multi-anvil apparatus. The ambient volume inferred from the compression curves is smaller than that of the starting material. Using the 3rd-order Birch-Murnaghan equation of state and the Mie-Grüneisen-Debye model, we have determined the thermoelastic parameters of the B3-SiC to be K0=228±3 GPa, K0',=4.4±0.4, q=0.27±0.37, where K0, K0' and q are the isothermal bulk modulus, its pressure derivative and logarithmic volume dependence of the Grüneisen parameter, respectively. Using the 3rd-order Birch-Murnaghan EOS with the thermal expansion coefficient, the thermoelastic parameters have been found as K0=221±3 GPa, K0',=5.2±0.4, α0=0.90±0.02 ⋅ 10-5 ⋅ K-1, where α0 is the thermal expansion coefficient at room pressure and temperature. We have determined that paired B3-SiC - MgO calibrants can be used to estimate pressure and temperature simultaneously in ultrahigh-pressure experiments up to 60 GPa.

Dietary exposure of the water flea Daphnia galeata to microcystin-LR.

Harmful substances like the cyanotoxin microcystin-leucine-arginine (MC-LR) are commonly found in eutrophic freshwater environments, posing risks to aquatic organisms. The water flea, Daphnia, is a well-established model organism for environmental toxicology research. Nevertheless, there is currently insufficient research on the genes that respond to MC-LR in Daphnia galeata. This study aimed to gain insights into the notable genes that react significantly to MC-LR. In this study, we generated an extensive RNA-Seq sequences isolated from the D. galeata HK strain, Han River in Korea. This strain was nourished with a diet of the green microalga Chlorella vulgaris and treated with pure MC-LR at a concentration of 36 ug/L. The transcriptome profile in response to the MC-LR treatment was obtained and 336 differentially expressed genes were subjected to Gene Ontology (GO) and euKaryotic Orthologous Groups of proteins analyses. GO enrichment analysis showed that chemical stimulus, amino sugar metabolic and catabolic process, oxidative stress, and detoxification were highly enriched, in reverse, proteolysis and fucosylation were underpresented. Detoxification process related genes such as peroxidase-like, chorion, and thyroid peroxidase-like were enriched for eliminating or neutralizing MC_LR from an organism's body. Furthermore, functional protein classification revealed an upregulation of lipid and inorganic ion transport processes, while amino acid and carbohydrate transport processes were found to be downregulated. These findings offer insights into how organisms respond to ecotoxic stimuli, providing valuable information for understanding adaptation or defense pathways.

Knowledge and Visual Differentiation Ability of the Pressure Injury Classification System and Incontinence-Associated Dermatitis among Hospital Nurses: A Descriptive Study.

This study investigated clinical nurses' knowledge and visual differentiation ability of the pressure injury classification system (PICS) and incontinence-associated dermatitis (IAD), additionally analyzing possible influencing factors. A convenience sample of 248 nurses took the PICS and IAD knowledge test (KT) and completed the visual differentiation ability test (VDAT), consisting of 21 photographs with clinical information. The overall mean score for correct answers was 12.65 ± 2.90 points in PICS and IAD KT and 11.43 ± 4.57 points in VDAT. Incorrect responses were most common for statements related to stage II, III, IAD for PICS and IAD KT, and deep tissue pressure injury (DTPI), unstageable, and stage III for VDAT. Significant correlations were found between PICS and IAD KT and VDAT (r = 0.252, p < 0.001). Factors affecting scores for VDAT were the scores of PICS and IAD KT, debridement experience in nursing patients with PI, and the management frequency of PI and IAD. Results indicate that nurses have an overall understanding of PICS and IAD, but low visual differentiation ability regarding stage III, DTPI, and unstageable PI. Continuing education is needed to further improve knowledge and visual differentiation ability for PICS and IAD.

Interdental cleaning and periodontal status among older Koreans: Findings from KNHANES VII.

OBJECTIVE: To assess the association between the usage of interdental cleaning and periodontal status among older people in Korea. BACKGROUND: In order to maintain oral health in older people, it is very important to use interdental cleaning devices. However, there is a lack of research on periodontal status and interdental cleaning device use in older people. METHODS: This study used data collected from the 7th National Health Nutrition Survey (KNHANES VII: 2016-2018). A total of 3426 older people adults aged 65 years or older were selected from 16 489 participants. Data on sociodemographic status (sex, age, level of education, income, residential area), personal health practice (subjective health status, smoking, physical activity, hypertension, and diabetes mellitus), oral health practice (subjective oral health status, tooth brushing frequency, dental visits, and chewing problem), the number of teeth and periodontitis were collected. Periodontitis was defined as having a World Health Organisation community periodontal index (CPI) code greater than or equal to three, and severe periodontitis was defined as a CPI code 4. Participants having a CPI code of 3 or 4 were considered to have periodontal disease in this study. Logistic regression analysis investigated the association between interdental cleaning devices usage and periodontitis controlling the confounding factors. RESULTS: Those who do not use dental floss had a higher rate of periodontal disease (AOR = 1.47, 95% confidence interval [CI]: 1.05 to 2.1). However, there were no significant differences by interdental brush use. In those with 20 or more teeth, non-users of dental floss had a higher risk of periodontitis in all models. Conversely, in those with fewer than 20 teeth, no significant differences were observed. CONCLUSIONS: Older people with mostly intact dentitions have better periodontal health if they clean between their teeth.

Oral health of older Koreans by region and family status in 2020-2021.

OBJECTIVE: To describe the oral health of older people by region and family status using data from the National Health and Nutrition Survey. BACKGROUND: As the ageing of Korean society intensifies, health inequalities based on region and family status are also deepening. METHODS: Data from the 8th National Health and Nutrition Survey (2020-2021) conducted by the Korea Centers for Disease Control and Prevention were used, and a total of 3437 older people aged 65 or older were selected as study participants. Chewing discomfort and oral health behaviours were assessed by region and family status using multivariable logistic regression analysis with the complex sample survey design. RESULTS: We found an association between living alone and greater chewing discomfort. Residing in rural areas was also associated with a higher prevalence of this. In urban areas, chewing discomfort was 1.27 times higher among older people living alone than in those not living alone, while in rural areas, the discomfort was 1.52 times higher among the older people who lived alone. CONCLUSIONS: Region and family status were associated with greater chewing discomfort in older people. In Korean society, where the number of single-person older people households is increasing, along with the ageing population, attention to resolving the disparities in oral health in older people is needed.

Proteomic Identification and Quantification of Secretory Proteins in Human Dermal Fibroblast-Conditioned Medium for Wound Repair and Hair Regeneration.

Background: Human dermal fibroblasts secrete numerous growth factors and proteins that have been suggested to promote wound repair and hair regeneration. Methods: Human dermal fibroblast-conditioned medium (DFCM) was prepared, and proteomic analysis was performed. Secretory proteins in DFCM were identified using 1-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis, in-gel trypsin protein digestion, and quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS). Identified proteins were analyzed using bioinformatic methods for the classification and evaluation of protein-protein interactions. Results: Using LC-MS/MS, 337 proteins were identified in DFCM. Among them, 160 proteins were associated with wound repair, and 57 proteins were associated with hair regeneration. Protein-protein interaction network analysis of 160 DFCM proteins for wound repair at the highest confidence score (0.9) revealed that 110 proteins were grouped into seven distinctive interaction networks. Additionally, protein-protein interaction network analysis of 57 proteins for hair regeneration at the highest confidence score revealed that 29 proteins were grouped into five distinctive interaction networks. The identified DFCM proteins were associated with several pathways for wound repair and hair regeneration, including epidermal growth factor receptor, fibroblast growth factor, integrin, Wnt, cadherin, and transforming growth factor-ß signaling pathways. Conclusion: DFCM contains numerous secretory proteins that comprise groups of protein-protein interaction networks that regulate wound repair and hair regeneration.

Prussian blue nanozymes coated with Pluronic attenuate inflammatory osteoarthritis by blocking c-Jun N-terminal kinase phosphorylation.

Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.

Effective Co-Creation Tool Development for Shared Understanding and Active Communication for Patients with Head and Neck Cancer.

To improve the quality of life of cancer patients, patient experience (PE) must be improved along with the overall treatment process. This study aimed to develop an effective and practical co-design tool to improve the healthcare service experience of patients with head and neck cancer (HNC) in various factors. The research consisted of four phases: (1) HNC PE categories for healthcare improvement were identified through systematic review, user interviews, and observation; (2) a focus group meeting was held to materialize the card design; (3) a structured and visual card set was developed for stakeholders to share the content and discuss improvements in PE effectively; (4) to evaluate the feasibility of the developed cards, a co-creation workshop with HNC medical staffs was conducted. From the workshop using insight cards, we identified the differences in the medical staff's and patients' perspectives on the factors for improving HNC PE in each stage of the treatment journey. Pat Exp Insight Cards as experience-based co-design (EBCD) tools can be useful for stakeholders to empathize with the specific pain points and needs of patients with HNC and to discuss improvement plans efficiently.

Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.

Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including 3 AGOs and 3 DICER-like proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.

Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy.

Targeted phototheranostic nanosystems involving both cancer-specific near-infrared (NIR) fluorescence imaging and NIR light-induced phototherapy have shown great potential to improve cancer detection and treatment. In this study, a bifunctional nanocomplex based on low-molecular-weight hyaluronic acid (LMW-HA) and chitosan oligosaccharide lactate (COL) conjugating a zwitterionic NIR dye (ZW800-1) was rationally designed and prepared, and it was simultaneously used to enhance tumor accumulation and photothermal therapy (PTT). When HA-COL-ZW nanocomplexes were intravenously injected into mice bearing NCI-H460 tumors, HA-COL-ZW revealed increased tumor accumulation with prolonged tumor retention. Moreover, the ZW800-1 incorporated in HA-COL-ZW nanocomplexes showed excellent capability to convert NIR light into heat energy at the tumor site, acting as a PTT agent. Therefore, the targeted phototherapeutic HA-COL-ZW nanocomplex is a biocompatible and effective photothermal nanoagent, which could be a good candidate for future clinical use.

Freshness Analysis of Raw Laver (Pyropia yenzoensis) Conserved under Supercooling Conditions.

Freezing raw laver is unsuitable for the laver industry due to process characteristics and economic problems. Therefore, this study attempted to investigate supercooled storage to extend the storage period without freezing, rather than refrigeration. To compare and analyze the storage ability of supercooling, the experiment was performed under refrigeration (5 °C), constant supercooling (CS, -2 °C), stepwise supercooling (SS, -2 °C), and freezing (-18 °C) conditions for 15 days, and the physicochemical changes according to the treatment and period were investigated. All SS samples, which were designed for stable supercooling, were kept in a supercooled state for 15 days. Two samples among the twelve total subjected to CS were frozen. At 9 days, the drip losses of the CS and SS samples were 6.32% and 6.48%, respectively, which was two times lower than that of refrigeration and three times lower than that of the frozen samples. The VBN of the refrigerated samples was 108.33 mg/100 g at 6 days, which exceeded the decomposition criterion. Simultaneously, the VBN of the other treatments was under the decomposition criterion of 30 mg/100 g. However, the VBN of both supercooling samples at 15 days increased to higher than the decomposition criterion. Regarding appearance, the refrigerated samples showed tissue destruction at 9 days, but tissue destruction of the CS and CC samples was observed at 15 days, and tissue destruction of the frozen samples was not observed until 15 days. Consequently, supercooling did not maintain quality for longer periods than freezing, but it did extend the shelf life more than refrigeration, and effectively preserved the quality for a short period.

Enhanced Tumor Uptake and Retention of Cyanine Dye-Albumin Complex for Tumor-Targeted Imaging and Phototherapy.

Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.

Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge.

Recurrent spillovers of α- and ß-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and ß-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and ß-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.

Conditions of the Stepwise Cooling Algorithm for Stable Supercooling Preservation and Freshness of Pork Loin.

Supercooling has the advantage of maintaining the freshness of foods without a phase transition. However, it is hard to sustain the supercooled state. Static temperature control, one of the various supercooling technologies, is used for stable supercooling storage. In this experiment, the effect of following external factors in maintaining the supercooled state of foods was investigated. Three main parameters had an effect on the supercooled state of food: (1) properly setting the lower-temperature limit of the supercooling algorithm, (2) slow cooling to the target temperature, and (3) minimizing temperature fluctuation. Accordingly, the following stepwise cooling algorithm for pork loin was designed: a lower-temperature limit of −3.0 °C and a storage period = 36 h followed by a lower-temperature limit of −3.5 °C for 24 h. The samples conserved at −3.0 °C displayed a 100% supercooled state. Physicochemical properties including drip loss, cooking loss, texture, color, total volatile basic nitrogen (TVBN), and total aerobic count (TAC) of pork loin were analyzed. The drip loss values of the supercooled meat samples were lower than those of the superchilled ones. Furthermore, TVBN and TAC of the treated samples were not significantly different from those of the fresh samples (p > 0.05). In conclusion, supercooling storage extended the freshness and quality of pork loin better than refrigerated storage.

Monitoring of an electrically induced signal in melon in relation to different environmental conditions in a smart farm.

A smart farm that automatically regulates environmental conditions such as temperature, humidity and nutrient supply will maximize crop production per unit area by using ICT-based technology. To control the environment in a smart greenhouse, plant growth should be monitored in real time. The physiological activity of a plant was monitored by receiving an electrical signal from inside the plant stem which changed when the plant absorbed nutrients and water. In this study, the environmental conditions in different areas of a smart farm were not much different, and growth parameters were not much affected by the environmental conditions of the area. However, a plant induced electrical signal (PIES) was associated with the atmospheric and media temperature and relative humidity although there was time lag of 6 ~ 7 h for the peaks of the PIES and other environmental conditions. Therefore, monitoring a PIES will make it possible to improve the growth environments in smart farms.

Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy.

Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.

Tumor Targeting with Methotrexate-Conjugated Zwitterionic Near-Infrared Fluorophore for Precise Photothermal Therapy.

Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy.