Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
Intraperitoneal(IP)delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models.Its advantage over intravenous(IV)administration was supported initially by observational...Intraperitoneal(IP)delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models.Its advantage over intravenous(IV)administration was supported initially by observational studies in treating recurrent ovarian cancer and eventually by better outcomes from IP vs.IV cisplatin in randomized studies in patients undergoing optimal surgical debulking at diagnosis.In the past two decades,with the introduction of novel anticancer interventions(such as taxanes,bevacizumab,inhibitors of DNA repair,and immune check point inhibitors),advantages of IP drug delivery are less clear and concerns are raised on cisplatin's therapeutic index.The discovery of BRCA genes and their key role in DNA repair,on the other hand,have strengthened the rationale for IP drug delivery:high grade serous cancers arising in the Mullerian epithelium in association with hereditary or somatic BRCA function inactivation are linked to peritoneal spread of cells that-while initially sensitive-are prone to emergence of platinum resistance.Therefore,selection of patients based on genomic features and focusing on the better tolerated IP carboplatin are ongoing.Recent examples of leveraging the peritoneal route include(1)targeting the cell membrane copper transport receptor-that is shared by platinums-by the combination of the proteasome inhibitor bortezomib and IP carboplatin;and(2)enhancing IP 5-fluoro-2-deoxyuridine cytotoxicity when coupled with PARP inhibition.展开更多
Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost a...Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.展开更多
Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-...Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.展开更多
In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spect...In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and展开更多
The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination ...The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination of the metal residues in the samples, the calculated actual daily exposure and concentration of the metal Pd, Ir, Rh, Ru, Mo, Ni, Cr, V, Cu, Mn, Fe and Zn that were less than the permitted daily exposures (PDE) and the limited concentration permitted in the EMEA guideline on the specification limits for residues of metal catalysts or metal reagents [1] . The metal residues can de adequately removed from the active pharmaceutical ingredients and the corresponding drugs. The trace metal residues will not affect human health and lead to the safety hazard by the intravenous injection.展开更多
Copolymer of divinyl ether and maleic anhydride (DVE-co-MA) derivatives of cis-platinum complexes were synthesized and characterized by elementary analysis, IR and XPS ( X-ray photoelectron spectroscopy). The behavior...Copolymer of divinyl ether and maleic anhydride (DVE-co-MA) derivatives of cis-platinum complexes were synthesized and characterized by elementary analysis, IR and XPS ( X-ray photoelectron spectroscopy). The behavior of the products in biological environment was also studied. UV-visible and fluorescence spectra show that these polymer derivatives are able to exchange ligands with selected nucleophilic groups in biological environment.展开更多
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
文摘Intraperitoneal(IP)delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models.Its advantage over intravenous(IV)administration was supported initially by observational studies in treating recurrent ovarian cancer and eventually by better outcomes from IP vs.IV cisplatin in randomized studies in patients undergoing optimal surgical debulking at diagnosis.In the past two decades,with the introduction of novel anticancer interventions(such as taxanes,bevacizumab,inhibitors of DNA repair,and immune check point inhibitors),advantages of IP drug delivery are less clear and concerns are raised on cisplatin's therapeutic index.The discovery of BRCA genes and their key role in DNA repair,on the other hand,have strengthened the rationale for IP drug delivery:high grade serous cancers arising in the Mullerian epithelium in association with hereditary or somatic BRCA function inactivation are linked to peritoneal spread of cells that-while initially sensitive-are prone to emergence of platinum resistance.Therefore,selection of patients based on genomic features and focusing on the better tolerated IP carboplatin are ongoing.Recent examples of leveraging the peritoneal route include(1)targeting the cell membrane copper transport receptor-that is shared by platinums-by the combination of the proteasome inhibitor bortezomib and IP carboplatin;and(2)enhancing IP 5-fluoro-2-deoxyuridine cytotoxicity when coupled with PARP inhibition.
基金supported by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
文摘Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.
文摘Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.
文摘In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and
基金The national SME technology innovation fund(11C26215305898)Kunming SME technology innovation fund(CJ2011040)
文摘The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination of the metal residues in the samples, the calculated actual daily exposure and concentration of the metal Pd, Ir, Rh, Ru, Mo, Ni, Cr, V, Cu, Mn, Fe and Zn that were less than the permitted daily exposures (PDE) and the limited concentration permitted in the EMEA guideline on the specification limits for residues of metal catalysts or metal reagents [1] . The metal residues can de adequately removed from the active pharmaceutical ingredients and the corresponding drugs. The trace metal residues will not affect human health and lead to the safety hazard by the intravenous injection.
基金Project supported by the Science Fund of the Chinese Academy of Sciences.
文摘Copolymer of divinyl ether and maleic anhydride (DVE-co-MA) derivatives of cis-platinum complexes were synthesized and characterized by elementary analysis, IR and XPS ( X-ray photoelectron spectroscopy). The behavior of the products in biological environment was also studied. UV-visible and fluorescence spectra show that these polymer derivatives are able to exchange ligands with selected nucleophilic groups in biological environment.
