There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the dru...There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.展开更多
OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From Septe...OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.展开更多
基金supported by the National Basic Research Program of China(973 Program,No.2012CB933600)the National Natural Science Foundation of China(Nos.81771964 and 82072051)+4 种基金the Shanghai Municipal Natural Science Foundation(No.15ZR1408500)funded by the Special Project of Clinical Research of Health Industry of Shanghai Municipal Health Commission(No.201940178)the Scientific Research Project of Hongkou District Health Committee of Shanghai(No.2002-17)the Clinical Research Project of Wu Jieping Medical Foundation(No.320.6750.2020-18-2)the Research Project of Shanghai Fourth People’s Hospital(No.sykyqd 00701&00702).
文摘There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.
基金Supported by the Clinical Medical Science and Technology Special of Jiangsu Provincial Science and Technology Project(No.BL2013039).
文摘OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.
