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Surface Modification of Carbon Quantum Dots by Fluorescein Derivative for Dual-Emission Ratiometric Fluorescent Hypochlorite Biosensing and in Vivo Bioimaging.
•A desirable ...dual-emission fluorescent nanoprobe was synthesized for the ratiometric fluorescence detection of ClO−.•The nanoprobe displayed low cytotoxicity, it was successfully applied for imaging ClO− in living cells and nude mice.•Compared with other proposed methods, this nanoprobe showed lower detection limit and larger linear ranges.
Surface modification of carbon quantum dots by fluorescein (FH-GA-CQDs) were synthesized for dual-emission ratiometric fluorescent ClO− biosensing and in vivo bioimaging. In the presence of ClO−, FH-GA-CQDs solution shows gradually decrease in the emission intensity at 413 nm and rapidly increase in the emission at 508 nm, corresponding to the blue-to-green emission color change. The detection mechanism is that the ClO− induces the ring-opening of FH units to form an oxadiazole structure, resulting in energy transferring from CQDs moiety to FH units. The energy transfer efficiency and energy transfer rate were estimated as 0.34 and 4.00 × 10−7 s−1, respectively. The results reveal that the FH-GA-CQDs have high sensitivity and selectivity for ClO− in the linear range extending from 0 to 70 μM with a detection limit as low as 93 nM. Meanwhile, the potency of the FH-GA-CQDs detecting ClO− in real water examples were validated by recoveries from 94% to 106% and semi-quantification determination of ClO− on fluorescent test strips. Most importantly, FH-GA-CQDs display low cytotoxicity and were successfully applied for sensing of ClO− in living cells and imaging of ClO− in nude mice.
Microwave sensitization nanoplatform, integrating multiple functional units for improving tumor selectivity, is of great significance for clinical tumor microwave treatment. Lanthanide europium metal ...organic framework (EuMOF) is expected to be a theranostic nanoplatform owing to its unique luminescent and microwave sensitization properties. However, it is difficult to be applied to complicated biological systems for EuMOF due to its rapid degradation induced by the solvent molecular and ionic environment. In this work, a luminescent EuMOF nanocomposite (EuMOF@ZIF/AP-PEG, named EZAP) was designed, which brought the multifunctional characteristics of microwave sensitization, fluorescence imaging and drug loading.
Lamellar EuMOF was synthesized by a hydrothermal method. Through the charge adsorption mechanism, the zeolite imidazole framework (ZIF) structure was intensively assembled on the surface of EuMOF to realize the protection. Then, through in-situ Apatinib drug loading and PEG modification, EZAP nanocomposite was finally obtained. Apatinib (AP) was a kind of chemotherapy drug approved by Food and Drug Administration for targeted therapy of tumors. PEG modification increased long-term circulation of EZAP nanocomposite. The physical and chemical structure and properties of EuMOF@ZIF (EZ) were systematically represented, indicating the successful synthesis of the nanocomposite. The toxic and side effects were negligible at a safe dose. The growth of human liver cancer cells and murine liver cancer cells in vitro was significantly inhibited, and the combined microwave-thermal therapy and chemotherapy in vivo achieved high anti-cancer efficacy. Moreover, EZAP nanocomposite possessed bright red fluorescence, which can be applied for tumor imaging in tumor-bearing mice in vivo.
Therefore, EZAP nanocomposite showed high microwave sensitization, excellent fluorescence properties and outstanding drug loading capacity, establishing a promising theranostic nanoplatform for tumor therapy and fluorescence imaging. This work proposes a unique strategy to design for the first time a multifunctional nanoplatform with lanthanide metal organic frameworks for biological applications in tumor therapy and diagnosis.
Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms ...worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.
In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. It is also known that the ...use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of ordinarily used compounds in cancer diagnosis and treatment.
Advances in the surface regulating of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future impact involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat or diagnose various kinds of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials than also can combine with thermal treatment.
This review examined some mesoporous silica nanoparticles and related nanomaterials and discussed the advantages of using nanocarriers in cancer therapy.
Nano-oncology and interventional oncology are both rapidly emerging fields in cancer therapies. Synergistic combination of the both fields offers drastic improvements in performance and efficacy of ...cancer killing agents.
This review is to overview the studies focusing on these two crossing fields and to give an overlook of their future development. Interventional techniques such as selective arterial catheterization, irreversible electroporation (IRE) and radiofrequency ablation (RFA) dramatically enhanced cancer targetability and anticancer efficacy of nanoparticles (NPs). Furthermore, synergistic effects were observed when using different interventional techniques together on NPs directed cancer treatments. On the other hand, NPs improved thermal ablation as well by fundamentally improving heating efficiency, facilitating heat triggered local drug delivery, and increasing cancer control in marginal peri-ablated zones and distant regions.
Crossing applications of the both techniques such as percutaneous delivery of near infrared (NIR) into deep tumors by needle insertion and conformal thermal ablation are highly anticipated.
Yellow-emissive carbon dots (Y-CDs) were prepared by a solvothermal method using anhydrous citric acid and 2,3-phenazinediamine as the starting materials. The Y-CDs display a 24% fluorescence quantum ...yield, a 188-nm Stokes’ shift and excellent stability. They are shown here to be excellent fluorescent probes for the determination of Ag(I) ion and glutathione (GSH). If exposed to Ag(I) ions, they are bound by the carboxy groups of the Y-CDs, and this causes quenching of fluorescence (with excitation/emission maxima at 380/568 nm) via a static quenching mechanism. This effect was used to design a fluorometric assay for Ag(I). The quenched fluorescence of the Y-CDs can be restored by adding GSH due to the high affinity of GSH for Ag(I). The calibration plot for Ag(I) is linear in the 1–4 μM Ag(I) concentration range, and the limit of detection is 31 nM. The respective values for GSH are 5–32 μM, and 76 nM, respectively. The method was applied to the detection of Ag(I) in spiked environmental water samples and gave recoveries ranging from 93 to 107%. It was also applied to the determination of GSH in tomatoes and purple grapes and gave satisfactory recoveries. The Y-CDs display low cytotoxicity and were successfully used to image Ag(I) and GSH in H1299 cells.
Graphical abstract
Schematic presentation of the mechanism of yellow fluorescent CDs for the detection of Ag
+
and glutathione.
The development of multifunctional nanoscale radiosensitizers has attracted a tremendous amount of attention, which can enhance the radiosensitization of tumor tissues and reduce unnecessary damage ...to the surrounding organs. However, the persistent hypoxia environment within the tumor limits their applications in radiotherapy. In this paper, a stable nanocomposite was engineered to overcome the hypoxia properties by using 1,4-benzenedicarboxylic acid produced from a Zr-MOF as a carbonic anhydrase IX (CA IX) inhibitor and quercetin (QU) as a radiosensitizer. QU was encapsulated into the Zr-MOF structure to achieve a synergetic dual sensitization therapy. Zr-MOF-QU exhibits an excellent potential of radiotherapy sensitization characteristics in vitro and in vivo from the γ-H2AX immunofluorescence staining and colony assays. The mechanisms of alleviating hypoxia-induced resistance and sensitizing tumor tissues to improve cell apoptosis from radiation were found to suppress CA IX expressions by the decomposition product from Zr-MOF and boost the sensitivity by QU in radiation therapy. Moreover, there was no significant systemic toxicity during the treatment, and the therapeutic outcome was assessed in animal models. Therefore, our results demonstrate a promising cancer treatment approach in the radiation field.
Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave ...thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy.
Carbon dots (CDs) as a fluorescent nanomaterial plays an important role in bioimaging and light-emitting devices, and its multifunctionalization will be a promising evolution. Here, by a freely ...rotatable single bond to connect materials with complementary functions together, a dual-function aggregation-induced emission (AIE) CDs (V-CDs) is obtained to visually monitor the dead of cancerous cells and inhibit the production of vascular endothelial growth factor (VEGF). The fluorescence of V-CDs will change between blue and green as the changes of environment viscosity based on the restriction of intramolecular rotation (RIR) effect. For another, the VEGF content decreased by about 3 times compared with the blank group after V-CDs was introduced. The co-administration group shows the best anti-cancer effect among the rest of control groups after Taxol was involved, and the same result are achieved in vitro and vivo. The performances of V-CDs make it possible to realize the potential of visualizing anti-cancer process.
•An AIE Carbon Dots capable of changing color with environmental viscosity is synthesized.•V-CDs can effectively inhibit VEGF for anticancer treatment.•Effects of inhibition, killing and monitoring of cancer cells were achieved.•Conception and application of CDs Complementary Function Modification.
Cisplatin (CDDP) is a widely used chemotherapeutic drug with proven efficacy for treating tumors. However, its use has been associated with severe side effects and eventually leads to drug ...resistance, thus limiting its clinical application in patients with ovarian cancer (OC). Herein, we aimed to investigate the success rate of reversing cisplatin resistance using a synthetic, multitargeted nanodrug delivery system comprising a Mn-based metal–organic framework (Mn-MOF) containing niraparib (Nira) and CDDP alongside transferrin (Tf) conjugated to the surface (Tf-Mn-MOF@Nira@CDDP; MNCT). Our results revealed that MNCT can target the tumor site, consume glutathione (GSH), which is highly expressed in drug-resistant cells, and then decompose to release the encapsulated Nira and CDDP. Nira and CDDP play a synergistic role in increasing DNA damage and apoptosis, exhibiting excellent antiproliferation, migration, and invasion activities. In addition, MNCT significantly inhibited tumor growth in tumor-bearing mice and exhibited excellent biocompatibility without side effects. Furthermore, it depleted GSH, downregulated multidrug-resistant transporter protein (MDR) expression, and upregulated tumor suppressor protein phosphatase and tensin homolog (PTEN) expression, consequently reducing DNA damage repair and reversing cisplatin resistance. These results indicate that multitargeted nanodrug delivery systems can provide a promising clinical approach to overcoming cisplatin resistance. This study provides an experimental basis for further investigation into multitargeted nanodrug delivery systems to reverse cisplatin resistance in patients with OC.
