scholarly journals Engineered Exosomes-Based Photothermal Therapy with MRI/CT Imaging Guidance Enhances Anticancer Efficacy through Deep Tumor Nucleus Penetration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1593
Author(s):  
Min Yang ◽  
Xiaohui Wang ◽  
Fang Pu ◽  
Ying Liu ◽  
Jia Guo ◽  
...  

Exosomes, as natural nanovesicles, have become a spotlight in the field of cancer therapy due to their reduced immunogenicity and ability to overcome physiological barriers. However, the tumor targeting ability of exosomes needs to be improved before its actual application. Herein, a multiple targeted engineered exosomes nanoplatform was constructed through rare earth element Gd and Dy-doped and TAT peptide-modified carbon dots (CDs:Gd,Dy-TAT) encapsulated into RGD peptide engineered exosomes (Exo-RGD), which were used to enhance the effect of cancer imaging diagnosis and photothermal therapy. In vitro and in vivo experiments showed that the resulting CDs:Gd,Dy-TAT@Exo-RGD could effectively accumulate at cancer site with an increased concentration owing to the targeting peptides modification and exosomes encapsulation. The tumor therapy effects of mice treated with CDs:Gd,Dy-TAT@Exo-RGD were heightened compared with mice from the CDs:Gd,Dy control group. After intravenous injection of CDs:Gd,Dy-TAT@Exo-RGD into tumor-bearing mice, the temperature of tumors rose to above 50 °C under NIR irradiation and the localized hyperpyrexia induced by CDs could remarkably ablate tumors. The survival rate of the mice was 100% after 60 days. In addition, the CDs:Gd,Dy-TAT@Exo-RGD exhibited higher MRI/CT imaging contrast enhancement of tumor sites than that of CDs:Gd,Dy. Our study identified that engineered exosomes are a powerful tool for encapsulating multiple agents to enhance cancer theranostic efficiency and provide insight into precise personalized nanomedicine.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hang Wu ◽  
Qi Jiang ◽  
Keyi Luo ◽  
Chunping Zhu ◽  
Mengmeng Xie ◽  
...  

AbstractThe combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO2@MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO2 NPs could catalyze the hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to generate endogenous oxygen (O2), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine.


2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.


2005 ◽  
Vol 09 (12) ◽  
pp. 835-840 ◽  
Author(s):  
Sun-Young Kwak ◽  
Dae-Seog Lim ◽  
Su-Mi Bae ◽  
Yong-Wook Kim ◽  
Joon-Mo Lee ◽  
...  

Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and induce apoptosis in many tumor cells. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Radachlorin®, in a cervical cancer model, TC-1 cells. When TC-1 cells were exposed to varied doses of Radachlorin® with light irradiation (6.25 J/cm2), PDT induced a dose-dependent growth inhibition of TC-1 cells. All of these cells were significantly damaged after light irradiation and categorized to be early and late apoptosis, as determined by annexin V staining. Radachlorin® localized primarily into the Golgi apparatus of cells in 12 h of the treatment, and weak fluorescence intensity was also detected in mitochondria. On the other hand, in the in vivo experiments, following light irradiation (100 J/cm2), retarded tumor growth was significant in mice treated with Radachlorin®, as compared to the control group. Taken together, we propose that PDT after the application of Radachlorin® may induce the Golgi apparatus-mediated apoptosis of cervical cancer cells in vitro, and also be effective in the mice system.


2020 ◽  
pp. 18-26
Author(s):  
I. Sani ◽  
A.A. Umar ◽  
S.A. Jiga ◽  
F. Bello ◽  
A. Abdulhamid ◽  
...  

Several studies have been reported on active peptides isolated from some medicinal plants, which were effective inhibitors against snake venom induced toxicities. Hence, the aim of this research work was to isolate, purify and characterize an antisnake venom plant peptide from Bauhinia rufescens seed that can serve as potential alternative to serum-based antivenins. B. rufescens seed was collected, duly identified, authenticated and processed. The peptide was isolated from the seed and purified using gel filtration chromatography and SDS-PAGE and then named as BRS-P19. Venom Phospholipase A2 (VPLA2) was used for the study and was isolated from Naja nigricollis venom. Albino mice of both sexes were used for in vivo experiments. They were divided into seven (7) groups of three (3) mice each. Group 1 served as normal control, group 2 were injected with VPLA2 only, group 3 and 4 were injected with VPLA2 then treated with BRS-P19 at doses of 0.2 and 0.4 mg/kg b.w. respectively, while mice in group 5 were injected with VPLA2 then treated with standard antivenin, group 6 and 7 were injected with VPLA2 followed by administration of ascorbic acid and α-tocopherol respectively. In all the groups, hepatic and renal levels of reactive oxygen species (ROS), lipid peroxidation (MDA) and activities of antioxidant enzymes were determined. The results showed that, the BRS-P19 has molecular weight of ~19kD. Its percentage in vitro inhibitory effect against VPLA2 was 91.85 ± 0.32%. For the in vivo study, the animals treated with 0.4 mg/kg b.w. of the BRS-P19 showed a significant (P<0.05) decrease in the hepatic and renal ROS and MDA levels when compared with the VPLA2 untreated group. But, the activities of the antioxidant enzymes in all the treated groups were significantly (P<0.05) increased by the BRS-P19 at 0.4 mg/kg b.w. when compared to the VPLA2 untreated group. Based on these findings, it has been established that, BRS-P19 has antisnake venom effect through inhibition of VPLA2 and antioxidant activity as the possible mechanisms of action.


Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 903
Author(s):  
Miklós Nagy ◽  
Gábor Szemán-Nagy ◽  
Alexandra Kiss ◽  
Zsolt László Nagy ◽  
László Tálas ◽  
...  

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.


Author(s):  
Bahman Rahimi Esboei ◽  
Masoud Keighobadi ◽  
Hajar Ziaei Hezarjaribi ◽  
Mahdi Fakhar ◽  
Ahmad Daryani ◽  
...  

Background: Toxoplasmosis is a disease that results from infection with an obligate intracellular T. gondii parasite, one of the world's most common parasites. Considering the complications of chemical drugs and the need for an appropriate drug combination for treatment of toxoplasmosis and also considering the antimicrobial potential of chitosan, as a natural source, this study was aimed to evaluate in vitro activity of commercial chitosan (CC) on T. gondii. Methods: In this experimental study, the tachyzoites of T. gondii was collected from the peritoneal exudates from infected Balb/c mice. The tachyzoites were diluted in phosphate buffer saline (PBS). Chitosan with low molecular weight was commercially purchased. Then, at concentrations of 10, 50, 100 and 200 µg/mL and after 30, 60, 120 and 180 minutes the viability of tachyzoites were determined by using trypan blue 0.1%. Anti-T.gondii activity of CC in all concentration was significantly higher than pyrimethamine as control group (P=0.05). Results: The concentration of 200 µg/mL of CC had the highest effects and killed 30.5, 52, 59 and 81.5% of tachyzoites after 30, 60, 120 and 180 minutes. Moreover, IC50 values of CC were 515, 171, 12.5 and <10 μg/mL in comparison with pyrimethamine as 58.82 μg/mL for 30, 60, 120, and 180 min of exposure time. Conclusion: Our results indicate chitosan in low molecular weight had potent activity against T. gondii tachyzoites and could be an appropriate candidate for treatment of at least acute toxoplasmosis, certainly, after complementary in vivo experiments.


2021 ◽  
Author(s):  
Jiajia Lv ◽  
Tianjiao Luan ◽  
Mingyan Yang ◽  
Mengmeng Wang ◽  
Jie Gao ◽  
...  

Abstract We developed an integrin αvβ3-specific liposomes, TR-conjugated liposomes (TR-LPs), loading IR783 for NIR imaging-guided both PTT and PDT. The TR-LPs was composed of soyabeanphosphatidylcholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N- [methoxy(polyethylene glycol)-2000] (DSPE-PEG) and TR-functionalized DSPE-PEG. IR783, NIR PTT/PDT diagnostic agents, were encapsulated in the hydrophilic core of the TR-LPs. DSPE-PEG had ability of reducing the absorption of TR-LPs by the reticuloendothelial system and increase the cycle time in body. RGD fragment on the TR peptide (TR = c(RGD)-AGYLLGHINLHHLAHL(Aib)HHIL-cys) enhanced the tumor selectivity of liposomes by specifically targeting integrin αvβ3-overexpressing cancer cells. Simultaneously, the rest of fragment on the TR peptide can be changed to the positive charge in the tumor microenvironment (pH 6.5), improving cellular uptake of photoagents at tumor site. We executed a set of in vitro and in vivo experiments to verify if, by functionalizing liposomes with an integrin αvβ3-specific and pH responding peptide, it is possible to achieve NIR imaging guided PTT/PDT for tumor treatment. TR-conjugated liposomes exhibited favorable physical and chemical stability, loading capacity, biocompatibility and tumor targeting. TR-LPs can safely and efficiently delivery IR783 to tumor sites to achieve their therapeutic function. IR783-TR-LPs is promising as a potentially safe and effective phototherapeutic agents for NIR fluorescence-guided tumor therapy applications.


Author(s):  
Mingzhu Chen ◽  
Ziqi Wang ◽  
Weilong Suo ◽  
Zhirong Bao ◽  
Hong Quan

Higher doses of radiotherapy (RT) are associated with resistance induction, therefore highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation. Our FH can deliver FeGA directly to the tumor site via intratumoral injection, where it is a reservoir-based system to conserve FeGA. The photothermal properties of FeGA steadily dissolve FH under laser irradiation, and, simultaneously, FeGA reacts with a large amount of H2O2 in the cell to produce OH (Fenton reaction) which is highly toxic to mitochondria, rendering the cell inactive and reducing radiotherapy resistance. In vivo and in vitro studies suggest that combining the FH and NIR irradiation with RT (2Gy) can significantly reduce tumor proliferation without side effects such as inflammation. To conclude, this is the first study to achieve combined chemodynamic therapy (CDT) and photothermal therapy (PTT) in situ treatment, and the best therapeutic effect can be obtained with a low-dose radiation combination, thus expanding the prospects of FeGA-based tumor therapy.


2009 ◽  
Vol 37 (06) ◽  
pp. 1153-1165 ◽  
Author(s):  
Jin-Xia Yang ◽  
Iduna Fichtner ◽  
Monika Becker ◽  
Margit Lemm ◽  
Xue-Mei Wang

The aim of the present work was to explore the anti-hepatoma effects of icariin both in vitro and in vivo and to elucidate its potential mechanism of action. The MTT assay was applied to test the anti-proliferative effects of icariin in vitro. HepG2 bearing NMRI nu/nu mice were used to test the anticancer effects of icariin in vivo. Immunohistochemical assay and flow cytometry assay (FACS) were applied to detect the possible mechanisms of action of icariin. MTT assay illustrated that icariin inhibited the proliferation of HepG2 cells in a concentration dependent manner; meanwhile, icariin inhibited the tumor growth in HepG2 bearing NMRI nu/nu mice. The tumor weight was inhibited by 55.6% and tumor volume was inhibited by 47.2%. Icariin did not influence the spleen and body weights or blood parameters. Immunohistochemical analysis indicated that the expressions of both CD31 and Ki67 in the icariin treated group were significantly lower than those in the control group (p < 0.01). FACS assay showed that icariin dramatically decreased the percentage of CD4+ and CD8+ cells in bone marrow and CD19+ cells in blood on day 8. On day 17, the percentage of CD8+ cells in blood was lower than those in the control group. CD4/CD8 ratio in icariin group was significantly elevated in bone marrow on day 17. Icariin showed anticancer efficacy both in vitro and in vivo. The possible mechanism of action could be related to its anti-angiogenesis and anti-proliferative effects in tumors.


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