Summary： The purpose of this study was to verify that a combination of mild hyperthermia and do- cetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment appr...Summary： The purpose of this study was to verify that a combination of mild hyperthermia and do- cetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor （ER）-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hy- perthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate （FITC）/propidium iodide （PI） staining. The effects of these combined treatments on cell cycle progres- sion in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cy- tometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase （MAPK） pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 （HSP70） and the multi-drug resistance （MDR） gene product P-glycoprotein （Pgp） were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration （IC50） of do- cetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 gmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from （23.66±3.59）% and （18.51±3.17）% in docetaxel treatment group to （47.12±6.73）% and （55.16±7.42）% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhib- ited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that pro- teins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lym- phoma 2 （Bcl-2） protein expression but slightly increased Bcl-2-associated X protein （Bax） expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel in- hibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.展开更多
Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinat...Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.展开更多
Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Her...Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.展开更多
Hyperthermia therapy is considered an effective anticancer strategy.However,high temperature can trigger an excessive inflammatory response,leading to tumor self-protection,immunosuppression,metastasis,and recurrence....Hyperthermia therapy is considered an effective anticancer strategy.However,high temperature can trigger an excessive inflammatory response,leading to tumor self-protection,immunosuppression,metastasis,and recurrence.To address this issue,we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy(mild PTT)based on cisplatin(DDP)and a ferrocene metal-organic framework(MOF-Fc)nanocomposite,which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses.Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA.The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity,magnifying mild hyperthermia effects via the radical oxygen species(ROS)-adenosine triphosphate(ATP)-HSP silencing pathway,with important implications for clinical hyperthermia therapy.展开更多
Harsh photothermal temperatures(>50℃)caused heating damage to the normal tissues and induced thermal resistance in cancer cells,which significantly limited the safety and efficacy of photothermal therapy(PTT)in ca...Harsh photothermal temperatures(>50℃)caused heating damage to the normal tissues and induced thermal resistance in cancer cells,which significantly limited the safety and efficacy of photothermal therapy(PTT)in cancer treatment.Mild hyperthermia(<42℃)combined with chemotherapy might solve this issue.Herein,a novel transition metal dichalcogenides nanostructure,namely,Bi_(2)Se_(3)/MoSe_(2)nanosaucers(BMNSs),was designed to produce mild photo-hyperthermia(mPTT)and combined with chemotherapy to improve the overall antitumor efficacy.The BMNSs were constituted by Bi_(2)Se_(3)hexagonal nanoplates and enclosed with MoSe_(2)nanosheets evenly.While the MoSe_(2)moiety endowed the nanoplatform with excellent photothermal efficacy,the Bi_(2)Se_(3)substrates provided large specific surface area to anchor more doxorubicin(DOX)molecules as chemotherapeutic agent.Under the stimuli of mPTT/tumor acidic microenvironment,the tumor-specific drug release and the enhanced chemotherapy could be realized,showing impressive therapeutic outcomes against 4T1 cells.The synergetic therapeutic mechanism might be attributed to the mPTT induced cell membrane permeability,and interestingly,the expression of heat shock proteins 70 was not elevated obviously after the synergetic therapy,thus to avoid the tumor thermal resistance and further improve the therapeutic effect.The in vivo anti-tumoral performance of the BMNSs was further studied and complete tumor eradication was achieved without any recurrence and biotoxicity.Not only demonstrating a paradigm of high therapeutic efficacy of mild hyperthermia and synergistic chemotherapy for precise cancer therapy,our findings proved that the cancer therapeutic effect can be improved with minimal side effects through exquisite designing of the microstructures and the physiochemical properties of the nanoplatform.展开更多
Purpose: In this project, we developed novel methods to quantify changes in tumor hypoxia following a mild tempera-ture hyperthermia (MTH) treatment in rat HT29 human colon adenocarcinoma xenograft. Materials and Meth...Purpose: In this project, we developed novel methods to quantify changes in tumor hypoxia following a mild tempera-ture hyperthermia (MTH) treatment in rat HT29 human colon adenocarcinoma xenograft. Materials and Methods: An exogenous hypoxia marker (IAZGP) was labeled with two radioisotopes of iodine (131I and 123I, respectively) to form two distinct tracers. The two tracers were injected into HT29-bearing nude rats 4-hour before and immediately following 41.5℃, 45-minute mild hyperthermia treatment. The distributions of the two hypoxia tracers were obtained by performing digital autoradiography on tumor sections, and image processing resulted in quantitative information at 50 μm pixel size. Results: Following the hyperthermia treatment, there was a remarkable decrease in hypoxia tracer binding. The average whole tumor hypoxia tracer targeted fraction in five animals changed from 30.3% ± 9.7% to 13.0% ± 5.3% after the hyperthermia treatment (P = 0.001). Detailed pixelby-pixel analysis of the image data revealed a decline in hypoxia tracer uptake after hyperthermia in most regions. However, there was concomitant emergence of some new regions of hypoxia identified by increased tracer uptake. In the control group, the overall hypoxia tracer targeted fraction remained almost constant, with some hypoxic tracer redistribution (putative acute hypoxia) observed. Conclusion: Reoxygenation occurred in the rat HT29 xenograft following MTH treatment. This was evident with preponderance of decreased hypoxia specific tracer uptake on tumor sections. Our methodology might be a useful tool in hypoxia study.展开更多
The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of p...The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells.展开更多
Photothermal therapy(PTT), typically ablates tumors via hyperthermia generated from photothermal agents(PTAs) under laser irradiation, has attracted great attentions in the past decades. Unfortunately,longstanding, fr...Photothermal therapy(PTT), typically ablates tumors via hyperthermia generated from photothermal agents(PTAs) under laser irradiation, has attracted great attentions in the past decades. Unfortunately,longstanding, frequent and high-power density laser irradiations are needed to maintain the hyperthermal status(>50 ℃) for efficient therapy, which will damage the skin and nearby healthy tissues. Suppressing cancer cells with a mild temperature elevation is more attractive and feasible for PTT. Recently,low-temperature photothermal therapy(LTPTT), which could inhibit tumor under mild hyperthermia, has been widely investigated by researchers. Herein, we systematically summarized the strategies to achieve LTPTT. Diverse PTAs including organic and inorganic materials reported for LTPTT were introduced. The established strategies for LTPTT were intensively described. Finally, the challenges as well as future perspectives in this field were discussed.展开更多
While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered selfrepairingautophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hy...While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered selfrepairingautophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel(NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundantNO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles(MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtainMNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability toperform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distributionand strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and thisprocess is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over onemonth and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel atthe tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NOeffectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronouslydestroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26colon tumors are completely eliminated without causing severe side-effects.展开更多
文摘Summary： The purpose of this study was to verify that a combination of mild hyperthermia and do- cetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor （ER）-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hy- perthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate （FITC）/propidium iodide （PI） staining. The effects of these combined treatments on cell cycle progres- sion in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cy- tometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase （MAPK） pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 （HSP70） and the multi-drug resistance （MDR） gene product P-glycoprotein （Pgp） were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration （IC50） of do- cetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 gmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from （23.66±3.59）% and （18.51±3.17）% in docetaxel treatment group to （47.12±6.73）% and （55.16±7.42）% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhib- ited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that pro- teins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lym- phoma 2 （Bcl-2） protein expression but slightly increased Bcl-2-associated X protein （Bax） expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel in- hibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.
基金supported by grants from the National Natural Science Foundation of China (No. 51903062)Guangdong Basic and Applied Basic Research Foundation (No.2020A1515011320)+1 种基金Science and Technology Projects of Guangzhou(No. 202102020757)Subject Construction Project of Basic Medical Sciences of Guangzhou Medical University (Nos.JCXKJS2021B07, JCXKJS2021D09)。
文摘Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.
基金financially supported by the National Natural Science Foundation of China (Nos.31771036,51703132)the Basic Research Program of Shenzhen (Nos.JCYJ20180507182413022,JCYJ20170412111100742)the Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (No.2018B030308003)。
文摘Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.
基金supported by the Postdoctoral Fellowship Program of CPSF[grant number BX20230068]the National Natural Science Foundation of China[grant numbers 82160341 and 82260345]+2 种基金the Natural Science Foundation of Guangxi[grant number 2022GXNSFDA035060]the China Postdoctoral Science Foundation[grant number 2023MD744192]the Key Research and Development Plan of Guangxi[grant number GUIKEAB22080066].
文摘Hyperthermia therapy is considered an effective anticancer strategy.However,high temperature can trigger an excessive inflammatory response,leading to tumor self-protection,immunosuppression,metastasis,and recurrence.To address this issue,we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy(mild PTT)based on cisplatin(DDP)and a ferrocene metal-organic framework(MOF-Fc)nanocomposite,which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses.Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA.The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity,magnifying mild hyperthermia effects via the radical oxygen species(ROS)-adenosine triphosphate(ATP)-HSP silencing pathway,with important implications for clinical hyperthermia therapy.
基金the National Natural Science Foundation of China for the financial support(Nos.51971116,81771981,and 32001005)Shaanxi Provincial Science and Technology Department for financial support(No.2021JM-476)Shaanxi Provincial Administration of Traditional Chinese Medicine for financial support(No.20211-ZZ-JC007).
文摘Harsh photothermal temperatures(>50℃)caused heating damage to the normal tissues and induced thermal resistance in cancer cells,which significantly limited the safety and efficacy of photothermal therapy(PTT)in cancer treatment.Mild hyperthermia(<42℃)combined with chemotherapy might solve this issue.Herein,a novel transition metal dichalcogenides nanostructure,namely,Bi_(2)Se_(3)/MoSe_(2)nanosaucers(BMNSs),was designed to produce mild photo-hyperthermia(mPTT)and combined with chemotherapy to improve the overall antitumor efficacy.The BMNSs were constituted by Bi_(2)Se_(3)hexagonal nanoplates and enclosed with MoSe_(2)nanosheets evenly.While the MoSe_(2)moiety endowed the nanoplatform with excellent photothermal efficacy,the Bi_(2)Se_(3)substrates provided large specific surface area to anchor more doxorubicin(DOX)molecules as chemotherapeutic agent.Under the stimuli of mPTT/tumor acidic microenvironment,the tumor-specific drug release and the enhanced chemotherapy could be realized,showing impressive therapeutic outcomes against 4T1 cells.The synergetic therapeutic mechanism might be attributed to the mPTT induced cell membrane permeability,and interestingly,the expression of heat shock proteins 70 was not elevated obviously after the synergetic therapy,thus to avoid the tumor thermal resistance and further improve the therapeutic effect.The in vivo anti-tumoral performance of the BMNSs was further studied and complete tumor eradication was achieved without any recurrence and biotoxicity.Not only demonstrating a paradigm of high therapeutic efficacy of mild hyperthermia and synergistic chemotherapy for precise cancer therapy,our findings proved that the cancer therapeutic effect can be improved with minimal side effects through exquisite designing of the microstructures and the physiochemical properties of the nanoplatform.
文摘Purpose: In this project, we developed novel methods to quantify changes in tumor hypoxia following a mild tempera-ture hyperthermia (MTH) treatment in rat HT29 human colon adenocarcinoma xenograft. Materials and Methods: An exogenous hypoxia marker (IAZGP) was labeled with two radioisotopes of iodine (131I and 123I, respectively) to form two distinct tracers. The two tracers were injected into HT29-bearing nude rats 4-hour before and immediately following 41.5℃, 45-minute mild hyperthermia treatment. The distributions of the two hypoxia tracers were obtained by performing digital autoradiography on tumor sections, and image processing resulted in quantitative information at 50 μm pixel size. Results: Following the hyperthermia treatment, there was a remarkable decrease in hypoxia tracer binding. The average whole tumor hypoxia tracer targeted fraction in five animals changed from 30.3% ± 9.7% to 13.0% ± 5.3% after the hyperthermia treatment (P = 0.001). Detailed pixelby-pixel analysis of the image data revealed a decline in hypoxia tracer uptake after hyperthermia in most regions. However, there was concomitant emergence of some new regions of hypoxia identified by increased tracer uptake. In the control group, the overall hypoxia tracer targeted fraction remained almost constant, with some hypoxic tracer redistribution (putative acute hypoxia) observed. Conclusion: Reoxygenation occurred in the rat HT29 xenograft following MTH treatment. This was evident with preponderance of decreased hypoxia specific tracer uptake on tumor sections. Our methodology might be a useful tool in hypoxia study.
文摘The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells.
基金financially supported by the Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices (No.2019B121203003)。
文摘Photothermal therapy(PTT), typically ablates tumors via hyperthermia generated from photothermal agents(PTAs) under laser irradiation, has attracted great attentions in the past decades. Unfortunately,longstanding, frequent and high-power density laser irradiations are needed to maintain the hyperthermal status(>50 ℃) for efficient therapy, which will damage the skin and nearby healthy tissues. Suppressing cancer cells with a mild temperature elevation is more attractive and feasible for PTT. Recently,low-temperature photothermal therapy(LTPTT), which could inhibit tumor under mild hyperthermia, has been widely investigated by researchers. Herein, we systematically summarized the strategies to achieve LTPTT. Diverse PTAs including organic and inorganic materials reported for LTPTT were introduced. The established strategies for LTPTT were intensively described. Finally, the challenges as well as future perspectives in this field were discussed.
基金supported by the National Natural Science Foundation of China(grant no.21975045)Natural Science Foundation of Shanghai(grant no.23ZR1406800).
文摘While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered selfrepairingautophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel(NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundantNO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles(MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtainMNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability toperform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distributionand strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and thisprocess is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over onemonth and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel atthe tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NOeffectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronouslydestroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26colon tumors are completely eliminated without causing severe side-effects.
