Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide,posing a severe threat to human health.Surgical resection remains the most preferred option for gastric cancer treat...Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide,posing a severe threat to human health.Surgical resection remains the most preferred option for gastric cancer treatment.However,for advanced gastric cancer,the curative effect of surgical resection is usually limited by the local recurrence,peritoneal carcinomatosis,or distal metastasis.Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection.Here,we designed a 5-fluorouracil(5-FU)and cis-platinum(DDP)co-delivery system based on a biodegradable temperature-sensitive hydrogel(PDLLA-PEG-PDLLA,PLEL)for intraoperative adjuvant combination chemotherapy of gastric cancer.This 5-FU+DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo.A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU+DDP/PLEL were observed against gastric cancer MKN45-luc cells.After intraperitoneal injection,the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model.The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well.What’s more,we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer,in which the intraoperative administration of 5-FU+DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors,resulting in an extended lifetime.Hence,this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer,that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.展开更多
Surgical resection remains the prefer option for bladder cancer treatment.However,the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis.Consequently,intravesical chemotherapy ...Surgical resection remains the prefer option for bladder cancer treatment.However,the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis.Consequently,intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect.Herein,a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed.GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly,then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM.The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release,and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo.Hence,this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.展开更多
基金We gratefully acknowledge financial support from the National Natural Science Foundation of China(U21A20417,31930067,and 31800797)the Sichuan Science and Technology Program(2022YFS0333,2022YFS0203)+1 种基金1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002)the Post-Doctor Research Project,West China Hospital,Sichuan University(2018HXBH066).
文摘Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide,posing a severe threat to human health.Surgical resection remains the most preferred option for gastric cancer treatment.However,for advanced gastric cancer,the curative effect of surgical resection is usually limited by the local recurrence,peritoneal carcinomatosis,or distal metastasis.Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection.Here,we designed a 5-fluorouracil(5-FU)and cis-platinum(DDP)co-delivery system based on a biodegradable temperature-sensitive hydrogel(PDLLA-PEG-PDLLA,PLEL)for intraoperative adjuvant combination chemotherapy of gastric cancer.This 5-FU+DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo.A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU+DDP/PLEL were observed against gastric cancer MKN45-luc cells.After intraperitoneal injection,the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model.The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well.What’s more,we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer,in which the intraoperative administration of 5-FU+DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors,resulting in an extended lifetime.Hence,this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer,that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.
基金financial support from the National Natural Science Foundation of China(U21A20417,31930067)1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘Surgical resection remains the prefer option for bladder cancer treatment.However,the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis.Consequently,intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect.Herein,a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed.GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly,then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM.The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release,and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo.Hence,this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.
