Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target ...Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.展开更多
Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarc...Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown.Methods：To investigate the clinical significance of BMPR2 and HIF1-αin osteosarcoma,we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry.Meanwhile,we conducted a follow-up to examine the metastatic behavior and overall survival（OS）of osteosarcoma patients.Results：Among 103 tissues,61 cases had BMPR2-positive expression and 57 cases had HIF1-αpositive expression.A significant correlation was noticed between BMPR2 and HIF1-αexpression in osteosarcoma specimens（P=0.035）.Receiver-operating characteristic（ROC）curves were calculated to investigate the predictive value of the two markers in tumor metastasis.By means of univariate and multivariate analysis,BMPR2 and HIF1-αexpression,as well as higher tumor grade,were identified as significant risk factors for OS in patients with osteosarcoma.Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-αpositive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining.Conclusions：It can be concluded that BMPR2 and HIF1-αexpression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.展开更多
基金supported by Guangdong Basic and Applied Basic Research Foundation(2023A1515010969)Natural Science Foundation of Top Talent of SZTU(GDRC202305).
文摘Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
基金supported by grants from the National Natural Science Foundation of China (No. 81572633)
文摘Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown.Methods：To investigate the clinical significance of BMPR2 and HIF1-αin osteosarcoma,we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry.Meanwhile,we conducted a follow-up to examine the metastatic behavior and overall survival（OS）of osteosarcoma patients.Results：Among 103 tissues,61 cases had BMPR2-positive expression and 57 cases had HIF1-αpositive expression.A significant correlation was noticed between BMPR2 and HIF1-αexpression in osteosarcoma specimens（P=0.035）.Receiver-operating characteristic（ROC）curves were calculated to investigate the predictive value of the two markers in tumor metastasis.By means of univariate and multivariate analysis,BMPR2 and HIF1-αexpression,as well as higher tumor grade,were identified as significant risk factors for OS in patients with osteosarcoma.Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-αpositive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining.Conclusions：It can be concluded that BMPR2 and HIF1-αexpression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.
