Hybrid teaching after COVID-19: advantages, challenges and optimization strategies.

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.

Metal-Organic Framework-Based Nano-Activators Facilitating Microwave Combined Therapy via a Divide-and-Conquer Tactic for Triple-Negative Breast Cancer.

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.

Reversal of Cisplatin Resistance in Ovarian Cancer by the Multitargeted Nanodrug Delivery System Tf-Mn-MOF@Nira@CDDP.

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.

Lanthanide europium MOF nanocomposite as the theranostic nanoplatform for microwave thermo-chemotherapy and fluorescence imaging.

BACKGROUNDS: 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. RESULTS: 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. CONCLUSION: 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.

Tumor reoxygenation for enhanced combination of radiation therapy and microwave thermal therapy using oxygen generation in situ by CuO nanosuperparticles under microwave irradiation.

As known, radiation therapy (RT) can exacerbate the degree of hypoxia of tumor cells, which induces serious resistance to RT and in turn, is the greatest obstacle to RT. Reoxygenation can restore the hypoxic state of tumor cells, which plays an important role in reshaping tumor microenviroment for achieving optimal therapeutic efficacy. Herein, we report for the first time that microwave (MW)-triggered IL-Quercetin-CuO-SiO2@ZrO2-PEG nanosuperparticles (IQuCS@Zr-PEG NSPs) have been used to achieve an optimal RT therapeutic outcomes by the strategy of upregulating tumor reoxygenation, i.e. hypoxic cells acquire oxygen and return to normal state. Methods: We prepared a promising multifunctional nanosuperparticle to upregulate tumor reoxygenation by utilizing CuO nanoparticle to generate oxygen under MW irradiation in the tumor microenvironment. The IQuCS@Zr-PEG NSPs were obtained by introducing CuO nanoparticles, MW sensitizer of 1-butyl-3-methylimidazolium hexafluorophosphate (IL), radiosensitizer of Quercetin (Qu) and surface modifier of monomethoxy polyethylene glycol sulfhyl (mPEG-SH, 5k Da) into mesoporous sandwich SiO2@ZrO2 nanosuperparticles (SiO2@ZrO2 NSPs). The release oxygen by IQuCS@Zr-PEG NSPs under MW irradiation was investigated by a microcomputer dissolved oxygen-biochemical oxygen demand detector (DO-BOD) test. Finally, we used the 99mTc-HL91 labeled reoxygenation imaging, Cellular immunofluorescence, immunohistochemistry, and TUNEL experiments to verify that this unique MW-responsive reoxygenation enhancer can be used to stimulate reshaping of the tumor microenvironment. Results: Through experiments we found that the IQuCS@Zr-PEG NSPs can persistently release oxygen under the MW irradiation, which upregulates tumor reoxygenation and improve the combined tumor treatment effect of RT and microwave thermal therapy (MWTT). Cellular immunofluorescence and immunohistochemistry experiments demonstrated that the IQuCS@Zr-PEG NSPs can downregulate the expression of hypoxia-inducible factor 1α (HIF-1α) under MW irradiation. The 99mTc-HL91 labeled reoxygenation imaging experiment also showed that the oxygen generated by IQuCS@Zr-PEG NSPs under MW irradiation can significantly increase the reoxygenation capacity of tumor cells, thus reshaping the tumor microenvironment. The high inhibition rate of 98.62% was achieved in the antitumor experiments in vivo. In addition, the IQuCS@Zr-PEG NSPs also had good computed tomography (CT) imaging effects, which can be used to monitor the treatment of tumors in real-time. Conclusions: The proof-of-concept strategy of upregulating tumor reoxygenation is achieved by MW triggered IQuCS@Zr-PEG NSPs, which has exhibited optimal therapeutic outcomes of combination of RT and MWTT tumor. Such unique MW-responsive reoxygenation enhancer may stimulate the research of reshaping tumor microenvironment for enhancing versatile tumor treatment.

4-aminoantipyrine modified carbon dots and their analytical applications through response surface methodology.

A sensitive and selective nanoprobe for detection of hypochlorite (OCl-) based on 4-aminoantipyrine (AAP) modified carbon dots (CDs-AAP) has been prepared. The CDs-AAP exhibit an emission peak at 484 nm when the excitation wavelength is 370 nm, accompanying 36 nm red shift compare with the pristine CDs. The addition of OCl- lead to the AAP on the surface of CDs experience a process of hydrazide hydrolysis and double bond addition, causing the singlet and triplet electrons of the excited state more closer in energy (ie, the energy difference between the two is reduced), eventually quenching the fluorescence of CDs due to heavy atomic effects. Central composite design (CCD) and response surface method (RSM) were used to optimize the detection variables of pH, incubation time and temperature. The designed model study indicated that the optimum detection conditions was pH 7.0, temperature 30 °C and incubation time 20 min, respectively. Under optimal conditions, the fluorescent intensity of the nanoprobe linearly responded to the OCl- concentration from 3 µM to 36 µM and the limit of detection was 40 nM. The proposed nanoprobe was successfully used to the detection of OCl- in tap water and pool water, and the recovery were in the range of 94% - 103%. In addition, the nanoprobe was also applied in imaging of VMSCs cells and labeling E.coli.

Novel fluorescein- and pyridine-conjugated schiff base probes for the recyclable real-time determination of Ce3+ and F.

The effect of aminopyridines substituted at different positions on the fluorescence properties deserves to be studied. Since 2-aminopyridyl-based probes have been reported, the effects of 3-aminopyridine and 4-aminopyridine on the performance of fluorescein probes were discussed in here. Two Schiff base fluorescein probes FN-1, FN-2 were designed and synthesized. Among them, since the ligand shows a highly selective and sensitive response to metal charge transfer (LMCT), the fluorescence of FN-1 can be quenched by Ce3+ ions in PBS buffer. At the same time, a specific precipitation reaction between Ce3+ and F- releases the free probe to restore the fluorescence of FN-1. Therefore, FN-1 can be used for the recyclable 'ON-OFF-ON' detection of Ce3+and F-. The detection limits for Ce3+and F- are 4.48 µM and 11.58 µM in concentration range of 0-50 µM and 0-150 µM. However, due to the para position of N and amino groups on 4-aminopyridine, the spatial structure of FN-2 cannot be complexed with ions, resulting in poor selectivity. Polyvinylidene fluoride (PVDF) membrane containing FN-1 were prepared for the real-time qualitative detection of Ce3+and F- in real water samples. FN-1 exhibits high water solubility and biocompatibility and has been successfully applied to biological imaging in vascular smooth muscle cells (VSMCs).

Quercetin-Modified Metal-Organic Frameworks for Dual Sensitization of Radiotherapy in Tumor Tissues by Inhibiting the Carbonic Anhydrase IX.

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.

Synthesis and spectral analysis of fluorescent probes for Ce4+ and OCl- ions based on fluorescein Schiff base with amino or hydrazine structure: Application in actual water samples and biological imaging.

Two Schiff base fluorescein probes (FDA, FDH) based on fluorescein-aldehyde and nitroaniline derivatives were synthesized. The effects of amino and hydrazine substituents in fluorescein backbones were examined via fluorescence and absorbance spectra. In the presence of Ce4+, the fluorescence of FDA was quenched due to the ligand to metal charge transfer (LMCT). Hypochloric acid can react with the CN bond, and blocking the photo induced electron transfer (PET) of FDH leads to enhancement of the fluorescence. FDA showed detection limits for Ce4+ and OCl- as low as 63 nM in concentration range of 0-4 µM. FDH showed detection limits for OCl- as low as 0.8 µM in concentration rang 0-100 µM. Polyvinylidene fluoride (PVDF) membrane containing the probes was prepared for the real-time qualitative detection of Ce4+ and OCl- in real water samples. The probes were successfully applied to biological imaging in vascular smooth muscle cells (VSMCs) and are expected to find applications in biosensing.

Yellow-emissive carbon dots with a large Stokes shift are viable fluorescent probes for detection and cellular imaging of silver ions and glutathione.

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.

Advances in the Use of Multifunctional Mesoporous Silica Nanoparticles and Related Nanomaterials as Carriers for the Cancer Treatment.

BACKGROUND: 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. OBJECTIVE: 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. CONCLUSION: This review examined some mesoporous silica nanoparticles and related nanomaterials and discussed the advantages of using nanocarriers in cancer therapy.

Combination of Multifunctional Nanoparticles and Interventional Techniques Makes Each Other Going Further in the Field of Cancer Treatment.

BACKGROUND: 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. OBJECTIVE: 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. CONCLUSION: 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.

Impact of postmastectomy radiation therapy in T1-2 breast cancer patients with 1-3 positive axillary lymph nodes.

The effect of postmastectomy radiotherapy (PMRT) on T1-2 breast cancer patients with 1-3 positive axillary lymph nodes is controversial up to now. The purpose of this study was to evaluate the impact of postmastectomy radiotherapy for these patients. The prognostic factor effecting locoregional free-survival (LRFS) was also analyzed. In the retrospective clinical data of 1674 eligible patients, survival analysis was performed using the method of Kaplan-Meier and the log-rank test. Cox regression analysis was applied to identify the significant prognostic factors. We found PMRT increased 5-year LRFS (p=0.003), but could not improve 5-year disease-free survival or overall survival statistically. For patients without PMRT, multivariate analysis revealed that age, lymph node ratio and molecule subtype were risk factors effecting LRFS. To further analyze the role of PMRT, we grouped all the patients into low risk group (0 or 1 risk factor) and high risk group (2 or 3 risk factors) depending on these risk factors. We found that in low-risk group, PMRT increased only 5-year LRFS (p=0.012). However, in high-risk group, PMRT increased both 5-year LRFS (p=0.005) and 5-year disease-free survival (p=0.033), but could not improve 5-year overall survival statistically. Thus, these data provide the evidence that PMRT could improve LRFS for T1-2 breast cancer patients with 1-3 positive axillary lymph nodes. Additionally, PMRT could improve LRFS and disease-free survival for high risk patients. Age, lymph node ratio and molecule subtype were high risk factors effecting LRFS in our study.

Short-term and long-term efficacy of 7 targeted therapies for the treatment of advanced hepatocellular carcinoma: a network meta-analysis: Efficacy of 7 targeted therapies for AHCC.

BACKGROUND: A variety of targeted drug therapies in clinical trials have been proven to be effective for the treatment of hepatocellular carcinoma (HCC). Our study aims to compare the short-term and long-term efficacies of different targeted drugs in advanced hepatocellular carcinoma (AHCC) treatment using a network meta-analysis approach. METHODS: PubMed, Embase, Ovid, EBSCO, and Cochrane central register of controlled trials were searched for randomized controlled trials (RCTs) of different targeted therapies implemented to patients with AHCC. And the retrieval resulted in 7 targeted drugs, namely, sorafenib, ramucirumab, everolimus, brivanib, tivantinib, sunitinib, and sorafenib+erlotinib. Direct and indirect evidence were combined to evaluate stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR), overall response ratio (ORR), overall survival (OS), and surface under the cumulative ranking curve (SUCRA) of patients with AHCC. RESULTS: A total of 11 RCTs were incorporated into our analysis, including 6594 patients with AHCC, among which 1619 patients received placebo treatment and 4975 cases had targeted therapies. The results revealed that in comparison with placebo, sorafenib, and ramucirumab displayed better short-term efficacy in terms of PR and ORR, and brivanib was better in ORR. Regarding long-term efficacy, sorafenib and sorafenib+erlotinib treatments exhibited longer OS. The data of cluster analysis showed that ramucirumab or sorafenib+erlotinib presented relatively better short-term efficacy for the treatment of AHCC. CONCLUSION: This network meta-analysis shows that ramucirumab and sorafenib+erlotinib may be the better targeted drugs for AHCC patients, and sorafenib+erlotinib achieved a better long-term efficacy.

Shape-Dependent Genotoxicity of Mesoporous Silica Nanoparticles and Cellular Mechanisms.

Although mesoporous silica nanoparticles (MSNs) are widely used in food products, cosmetics and nanomedicines as vector for drug delivery, data on their potential genotoxocity are limited. The aim of this study was to investigate the cytotoxic and genotoxic potentials of MSNs of different shapes, and to establish a high-throughput screening method for nanoparticles. We used functional macrophage receptor with collagenous structure (MARCO)-expressing DNA repair deficient chicken DT40 cells, which are designed to internalize nanoparticles and to be deficient in several specific DNA repair pathways. In addition, we verified the validity of this assay by analyzing and characterizing the genotoxicity of sphere- or rod-shaped MSNs. We demonstrated that both sphere- and rod-shaped MSNs were cytotoxic, and that this effect was greater in FEN1(-/-) and REV3(-/-) cells compared with wild-type cells. Effects of rod-shaped MSNs were more severe compared with sphere-shaped MSNs. Furthermore, MSNs induced oxidative damage and a larger number of mitotic chromosomal aberrations in repair-deficient cells compared with repair-proficient cells. Taken together, this assay system using the chimeric receptor-expressing DNA repair-deficient DT40 cells provides a sensitive method to screen for genotoxicity of MSNs.

In Vivo Magnetic Resonance Imaging and Microwave Thermotherapy of Cancer Using Novel Chitosan Microcapsules.

Herein, we develop a novel integrated strategy for the preparation of theranostic chitosan microcapsules by encapsulating ion liquids (ILs) and Fe3O4 nanoparticles. The as-prepared chitosan/Fe3O4@IL microcapsules exhibit not only significant heating efficacy in vitro under microwave (MW) irradiation but also obvious enhancement of T2-weighted magnetic resonance (MR) imaging, besides the excellent biocompatibility in physiological environments. The chitosan/Fe3O4@IL microcapsules show ideal temperature rise and therapeutic efficiency when applied to microwave thermal therapy in vivo. Complete tumor elimination is realizing after MW irradiation at an ultralow power density (1.8 W/cm(2)), while neither the MW group nor the chitosan microcapsule group has significant influence on the tumor development. The applicability of the chitosan/Fe3O4@IL microcapsules as an efficient contrast agent for MR imaging is proved in vivo. Moreover, the result of in vivo systematic toxicity shows that chitosan/Fe3O4@IL microcapsules have no acute fatal toxicity. Our study presents an interesting type of multifunctional platform developed by chitosan microcapsule promising for imaging-guided MW thermotherapy.

Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy.

Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models.Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting.A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy.In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models.

Layered MoS2 Hollow Spheres for Highly-Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors.

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand-new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near-infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as-prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor-targeting delivery and cancer theranostic application.

Encapsulating Ionic Liquid and Fe3O4 Nanoparticles in Gelatin Microcapsules as Microwave Susceptible Agent for MR Imaging-guided Tumor Thermotherapy.

The combination of therapies and monitoring the treatment process has become a new concept in cancer therapy. Herein, gelatin-based microcapsules have been first reported to be used as microwave (MW) susceptible agent and magnetic resonance (MR) imaging contrast agent for cancer MW thermotherapy. Using the simple coacervation methods, ionic liquid (IL) and Fe3O4 nanoparticles (NPs) were wrapped in microcapsules, and these microcapsules showed good heating efficacy in vitro under MW irradiation. The results of cell tests indicated that gelatin/IL@Fe3O4 microcapsules possessed excellent compatibility in physiological environments, and they could effectively kill cancer cells with exposure to MW. The ICR mice bearing H22 tumors treated with gelatin/IL@Fe3O4 microcapsules were obtained an outstanding MW thermotherapy efficacy with 100% tumor elimination under ultralow density irradiation (1.8 W/cm(2), 450 MHz). In addition, the applicability of the microcapsules as an efficient contrast agent for MR imaging in vivo was evident. Therefore, these multifunctional microcapsules have a great potential for MR imaging-guided MW thermotherapy.