Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid li...Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5-5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ± 1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.展开更多
Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can b...Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner.In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.展开更多
A new copper complex [Cu(pdc)(bpy)]·H2 O(1, H2 pdc = 3,5-pyridinedicarboxylic acid, bpy = 2,2-bipyridine) has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, elemental...A new copper complex [Cu(pdc)(bpy)]·H2 O(1, H2 pdc = 3,5-pyridinedicarboxylic acid, bpy = 2,2-bipyridine) has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, UV-vis spectroscopy and magnetic measure- ments. Complex 1 crystallizes in monoclinic system, space group P21 /c, a = 10.893(2), b = 7.3641(15), c = 1.9921(4), β = 92.16(3), V = 1596.9(6)3, Dc = 1.676 g/cm3, Mr = 402.84, Z = 4, F(000) = 820, μ = 1.404 mm-1, the final R = 0.0237 and wR = 0.0693. The Cu(II) ion is five-coordinated by two O atoms from two pdc ligands, one N atom from another pdc ligand and two N atoms from the bpy ligand. The pdc anion, which acts as a tridentate ligand, links three Cu ions, forming(3,3)-connected two-dimensional(2D) sheets. We also studied the electronic structure and orbital energies of complex 1 by DFT methods, and the results are consistent with UV-vis spectrum.展开更多
Cancer immunotherapy is capable of stimulating the body's immune system to selectively attack cancer cells and has the advantages of high efficacy and low toxicity over traditional therapies.Numerous immunotherapi...Cancer immunotherapy is capable of stimulating the body's immune system to selectively attack cancer cells and has the advantages of high efficacy and low toxicity over traditional therapies.Numerous immunotherapies have been approved for clinical applications or clinical trials,including immune checkpoint blockade,adoptive cell therapy,recombinant cytokines,bispecific T-cell engagers,and cancer vaccines.展开更多
Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous...Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.展开更多
Dear Editor, Hepatitis C virus (HCV) infection, which causes hepatitis C and can chronically lead to serious and life-threatening dis- eases including liver cirrhosis and hepatocellular carcinoma (Lauer and Walker,...Dear Editor, Hepatitis C virus (HCV) infection, which causes hepatitis C and can chronically lead to serious and life-threatening dis- eases including liver cirrhosis and hepatocellular carcinoma (Lauer and Walker, 2001), is a rising global health problem. More than 170 million people are infected by HCV worldwide and 3-4 million people are infected each year. No effective vaccines are available to prevent HCV infection. Moreover, HCV is a fast mutating RNA virus with seven distinct genotypes and many subtypes within each genotype. The high degree of genetic diversity can lead to further viral resistance to the current therapies within individual patients (Li et al., 2012). Hence, there remains a strong desire in the medical community to explore new therapeutic opportunities.展开更多
Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. To date, the survival of patients with HCC has not improved because of the insensitivity of HCC to conventional treatments....Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. To date, the survival of patients with HCC has not improved because of the insensitivity of HCC to conventional treatments. Sonodynamic therapy (SDT) is a promising new approach that shows remarkable potential in the treatment of HCC. Here, we designed a simple, biocompatible, and multifunctional nanosystem that combines SDT and chemotherapy to treat HCC. This nanosystem, called HPDF nanoparticles, had a core-shell structure in which hematoporphyrin (HP) was complexed with doxorubicin (DOX) to form the hydrophobic core and the surface was coated with Pluronic F68 to form the hydrophilic shell. In HCC cells, HPDF nanoparticles in combination with ultrasonic irradiation (1.0 MHz, 1.5 W/cm2, 30 s) exhibited potent cytotoxicity, resulting from the synergistic effects of a large amount of reactive oxygen species generated from HP and DOX-induced DNA damage. Notabl~ HPDF nanoparticles in combination with ultrasonic irradiation significantly reversed drug resistance in Nanog-positive cancer stem cells (CSCs) in HCC. In nude mice bearing HCC tumors, HPDF nanoparticles efficiently accumulated in the tumors and reached the maximum levels within 6-8 h, post intravenous injection. HPDF nanoparticles, in combination with ultrasonic irradiation (1.0 MHz, 3 W/cm2, 5 min), suppressed tumor growth, angiogenesis, and collagen deposition, considerably. In summary, our results show that HPDF nanoparticles can effectively combine SDT and chemotherapy to inhibit HCC growth and progression through multiple mechanisms in both cellular and animal models.展开更多
Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)...Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)show many advantages in TNBC treatment,and their combination with chemotherapy can achieve synergistic therapeutic effects.In the present study,a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane(LPHM)and dendritic large pore mesoporous silicon nanoparticles(DLMSNs).A near infrared(NIR)fluorescent dye IR780 and a chemotherapeutic drug doxorubicin(DOX)were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780(DDI)nanoparticles(NPs),followed by camouflage with LPHM to obtain LPHM@DDI NPs.Through the mediation of LPHM,LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo.Upon NIR laser irradiation,LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells,and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis.These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy.Altogether,this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.展开更多
Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent p...Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future "drug-of-choice". Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs (an exceedingly low 1.2%), reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.展开更多
While drug resistance appears to be an inevitable problem of an increasing number of anticancer drugs in monotherapy, combination drug therapy has become a prosperous method to reduce the administered total drug dosag...While drug resistance appears to be an inevitable problem of an increasing number of anticancer drugs in monotherapy, combination drug therapy has become a prosperous method to reduce the administered total drug dosages as well as overcome the drug resistance of carcinoma cells. Curcumin, considered to possess multi- faceted roles in cancer treatment according to its multiple anti-neoplastic mechanisms as a depressor of chemo- resistance, can significantly facilitate its anti-cancer functions and improve therapeutic effects via combination usage with a variety of other drugs with different reaction mechanisms. To explore this possibility, four anti-cancer chemotherapeutic agents that all possess a certain degree of drug resistance problems, including three tyrosine kinase inhibitors (erlotinib, sunitinib and sorafenib) that are acting on different cell pathways and a typical anticancer drug doxorubicin, were combined with curcumin individually to examine the synergistic anti-tumor effect both in vitro and in vivo. Results revealed that sunitinib combined with curcumin at the molar ratio of 0.46 yielded the most potent synergistic effect in vitro, and was therefore chosen for further animal evaluation. To further enhance the anti- cancer effect, bovine serum albumin (BSA) nanoparticles were utilized as a carrier to deliver the selected drug combination in situ. Preliminary in vivo findings confirmed our hypothesis of being able to maintain a similar injected drug ratio for prolonged time periods in tested animals by our approach, thereby maximizing the therapeutic potency yet minimizing the toxicity of these drugs. This work could open up a new avenue on combination drug therapy and realization the clinical utility of such drugs.展开更多
文摘Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5-5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ± 1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.
基金supported by the National Natural Science Foundation of China(Grant No.81573005 and 81371671)
文摘Sonodynamic therapy(SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner.In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.
基金Supported by Natural Science Foundation of Hebei Province(No.E2013501135)program for New Century Excellent Talents in University(NCET-10-0304)
文摘A new copper complex [Cu(pdc)(bpy)]·H2 O(1, H2 pdc = 3,5-pyridinedicarboxylic acid, bpy = 2,2-bipyridine) has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, UV-vis spectroscopy and magnetic measure- ments. Complex 1 crystallizes in monoclinic system, space group P21 /c, a = 10.893(2), b = 7.3641(15), c = 1.9921(4), β = 92.16(3), V = 1596.9(6)3, Dc = 1.676 g/cm3, Mr = 402.84, Z = 4, F(000) = 820, μ = 1.404 mm-1, the final R = 0.0237 and wR = 0.0693. The Cu(II) ion is five-coordinated by two O atoms from two pdc ligands, one N atom from another pdc ligand and two N atoms from the bpy ligand. The pdc anion, which acts as a tridentate ligand, links three Cu ions, forming(3,3)-connected two-dimensional(2D) sheets. We also studied the electronic structure and orbital energies of complex 1 by DFT methods, and the results are consistent with UV-vis spectrum.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82273499 and 81972903)the Talent Excellence Program from Tianjin Medical University。
文摘Cancer immunotherapy is capable of stimulating the body's immune system to selectively attack cancer cells and has the advantages of high efficacy and low toxicity over traditional therapies.Numerous immunotherapies have been approved for clinical applications or clinical trials,including immune checkpoint blockade,adoptive cell therapy,recombinant cytokines,bispecific T-cell engagers,and cancer vaccines.
基金supported by the National Natural Science Foundation of China(No.12074284)the Natural Science Foundation of Tianjin City,China(No.20JCYBJC00170).
文摘Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.
文摘Dear Editor, Hepatitis C virus (HCV) infection, which causes hepatitis C and can chronically lead to serious and life-threatening dis- eases including liver cirrhosis and hepatocellular carcinoma (Lauer and Walker, 2001), is a rising global health problem. More than 170 million people are infected by HCV worldwide and 3-4 million people are infected each year. No effective vaccines are available to prevent HCV infection. Moreover, HCV is a fast mutating RNA virus with seven distinct genotypes and many subtypes within each genotype. The high degree of genetic diversity can lead to further viral resistance to the current therapies within individual patients (Li et al., 2012). Hence, there remains a strong desire in the medical community to explore new therapeutic opportunities.
基金This research was supported by the National Natural Science Foundation of China (Nos. 81573005, 81371671, and 81472683) and the National High-tech R&D Program of China (863 Program, No. 2015AA020403). The authors thank Prof. C. Qian (Third Military Medical University, Chongqing, China) for providing NanogPos CSCs and NanogNeg cells.
文摘Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. To date, the survival of patients with HCC has not improved because of the insensitivity of HCC to conventional treatments. Sonodynamic therapy (SDT) is a promising new approach that shows remarkable potential in the treatment of HCC. Here, we designed a simple, biocompatible, and multifunctional nanosystem that combines SDT and chemotherapy to treat HCC. This nanosystem, called HPDF nanoparticles, had a core-shell structure in which hematoporphyrin (HP) was complexed with doxorubicin (DOX) to form the hydrophobic core and the surface was coated with Pluronic F68 to form the hydrophilic shell. In HCC cells, HPDF nanoparticles in combination with ultrasonic irradiation (1.0 MHz, 1.5 W/cm2, 30 s) exhibited potent cytotoxicity, resulting from the synergistic effects of a large amount of reactive oxygen species generated from HP and DOX-induced DNA damage. Notabl~ HPDF nanoparticles in combination with ultrasonic irradiation significantly reversed drug resistance in Nanog-positive cancer stem cells (CSCs) in HCC. In nude mice bearing HCC tumors, HPDF nanoparticles efficiently accumulated in the tumors and reached the maximum levels within 6-8 h, post intravenous injection. HPDF nanoparticles, in combination with ultrasonic irradiation (1.0 MHz, 3 W/cm2, 5 min), suppressed tumor growth, angiogenesis, and collagen deposition, considerably. In summary, our results show that HPDF nanoparticles can effectively combine SDT and chemotherapy to inhibit HCC growth and progression through multiple mechanisms in both cellular and animal models.
基金the National Natural Science Foundation of China(Nos.81972903,12074284 and 81803101)the Natural Science Foundation of Tianjin City of China(Nos.18JCZDJC33400 and 19JCQNJC12300)the Excellent Talent Project of Tianjin Medical University.
文摘Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)show many advantages in TNBC treatment,and their combination with chemotherapy can achieve synergistic therapeutic effects.In the present study,a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane(LPHM)and dendritic large pore mesoporous silicon nanoparticles(DLMSNs).A near infrared(NIR)fluorescent dye IR780 and a chemotherapeutic drug doxorubicin(DOX)were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780(DDI)nanoparticles(NPs),followed by camouflage with LPHM to obtain LPHM@DDI NPs.Through the mediation of LPHM,LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo.Upon NIR laser irradiation,LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells,and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis.These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy.Altogether,this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.
文摘Successful development of a new drug is prohibitively expensive, and is estimated to cost approxi- mately S100-500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attri- butes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appro- priately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10^6- 10^8 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future "drug-of-choice". Yet, among the 〉 10000 drugs that are currently available, only -150 of them belong to these bio- macromolecular drugs (an exceedingly low 1.2%), reflect- ing the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio- macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collec- tively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.
基金Acknowledgements This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 81402856, A3 project- 81361140344, and 21402143). Professors Lee SJ and Shin MC are participants from the Korean A3 Foresight Program sponsored by NRF. This research was also partially sponsored by Tianjin Municipal Science and Technology Commission (15JCYBJC28700 and 15JCQNJC13600). This research was partially supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology Grants NRF- 2015R1A6A3A01020598 and NRF-2015RIC1A1A02036781.
文摘While drug resistance appears to be an inevitable problem of an increasing number of anticancer drugs in monotherapy, combination drug therapy has become a prosperous method to reduce the administered total drug dosages as well as overcome the drug resistance of carcinoma cells. Curcumin, considered to possess multi- faceted roles in cancer treatment according to its multiple anti-neoplastic mechanisms as a depressor of chemo- resistance, can significantly facilitate its anti-cancer functions and improve therapeutic effects via combination usage with a variety of other drugs with different reaction mechanisms. To explore this possibility, four anti-cancer chemotherapeutic agents that all possess a certain degree of drug resistance problems, including three tyrosine kinase inhibitors (erlotinib, sunitinib and sorafenib) that are acting on different cell pathways and a typical anticancer drug doxorubicin, were combined with curcumin individually to examine the synergistic anti-tumor effect both in vitro and in vivo. Results revealed that sunitinib combined with curcumin at the molar ratio of 0.46 yielded the most potent synergistic effect in vitro, and was therefore chosen for further animal evaluation. To further enhance the anti- cancer effect, bovine serum albumin (BSA) nanoparticles were utilized as a carrier to deliver the selected drug combination in situ. Preliminary in vivo findings confirmed our hypothesis of being able to maintain a similar injected drug ratio for prolonged time periods in tested animals by our approach, thereby maximizing the therapeutic potency yet minimizing the toxicity of these drugs. This work could open up a new avenue on combination drug therapy and realization the clinical utility of such drugs.
基金supported by the National Key Research and Development Program of China(2017YFB0307000)the National Natural Science Foundation of China(51973093,U1533122 and 51773094)+5 种基金the Natural Science Foundation of Tianjin(18JCZDJC36800)the Science Foundation for Distinguished Young Scholars of Tianjin(18JCJQJC46600)the Fundamental Research Funds for the Central Universities(63171219)the State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,Donghua University(LK1704)the National Special Support Plan for High-level Talents people(C041800902)the Eugene McDermott Graduate Fellows Program。