Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer,although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cance...Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer,although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cancerous and normal cells.Although nucleic acid nanomaterials are emerging as a promising drug delivery strategy,their clinical applications are limited by rapid degradation by nucleases and difficulties in targeting cancer cells.In this study,we have developed a Rhein-loaded aptamer-based DNA nanotube(DNT-S6@Rhein)for the targeted and efficient therapy of non-small cell lung cancer.Through the palindrome segments,two specified oligonucleotides were hybridized and folded into the well-defined nanotubes(DNT-S6),with the S6 aptamer distributed outside.The obtained nanotubes exhibited excellent serum stability and targeting ability towards A549 cells due to the firm structure and decoration of the S6 aptamer.Rhein,as an antitumor drug and DNA intercalator,can be effectively inserted into the DNT-S6.The drug-loaded nanotubes rapidly disassembled in intracellular environment and then the released Rhein was found to activate cellular apoptotic process and significantly suppress proliferation,migration and invasion of A549 cells.Moreover,DNT-S6@Rhein could efficiently accumulate in tumor regions,offering compelling therapeutic efficacy and biocompatibility under both in vitro and in vivo settings.These findings of this study provide a promising strategy for mitigating the inevitable systemic side-effects of chemotherapy and expand the potential application of DNA nanostructure on targeted drug delivery.展开更多
Pulmonary Hypertension(PH)is a global health problem that affects about 1%of the global population.Animal models of PH play a vital role in unraveling the pathophysiological mechanisms of the disease.The present study...Pulmonary Hypertension(PH)is a global health problem that affects about 1%of the global population.Animal models of PH play a vital role in unraveling the pathophysiological mechanisms of the disease.The present study proposes a Kernel Extreme Learning Machine(KELM)model based on an improved Whale Optimization Algorithm(WOA)for predicting PH mouse models.The experimental results showed that the selected blood indicators,including Haemoglobin(HGB),Hematocrit(HCT),Mean,Platelet Volume(MPV),Platelet distribution width(PDW),and Platelet–Large Cell Ratio(P-LCR),were essential for identifying PH mouse models using the feature selection method proposed in this paper.Remarkably,the method achieved 100.0%accuracy and 100.0%specificity in classification,demonstrating that our method has great potential to be used for evaluating and identifying mouse PH models.展开更多
基金the support from the First Affiliated Hospital of Wenzhou Medical University Medical Research Center。
文摘Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer,although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cancerous and normal cells.Although nucleic acid nanomaterials are emerging as a promising drug delivery strategy,their clinical applications are limited by rapid degradation by nucleases and difficulties in targeting cancer cells.In this study,we have developed a Rhein-loaded aptamer-based DNA nanotube(DNT-S6@Rhein)for the targeted and efficient therapy of non-small cell lung cancer.Through the palindrome segments,two specified oligonucleotides were hybridized and folded into the well-defined nanotubes(DNT-S6),with the S6 aptamer distributed outside.The obtained nanotubes exhibited excellent serum stability and targeting ability towards A549 cells due to the firm structure and decoration of the S6 aptamer.Rhein,as an antitumor drug and DNA intercalator,can be effectively inserted into the DNT-S6.The drug-loaded nanotubes rapidly disassembled in intracellular environment and then the released Rhein was found to activate cellular apoptotic process and significantly suppress proliferation,migration and invasion of A549 cells.Moreover,DNT-S6@Rhein could efficiently accumulate in tumor regions,offering compelling therapeutic efficacy and biocompatibility under both in vitro and in vivo settings.These findings of this study provide a promising strategy for mitigating the inevitable systemic side-effects of chemotherapy and expand the potential application of DNA nanostructure on targeted drug delivery.
基金the National Natural Science Foundation of China(82003831,62076185 and U1809209)the Project of Health Commission of Zhejiang Province(2020KY177)+2 种基金the Wenzhou Technology Foundation(Y2020002)the Natural Science Foundation of Zhejiang Province(LZ22F020005)the First Affiliated Hospital of Wenzhou Medical University Youth Excellence Project(QNYC114).
文摘Pulmonary Hypertension(PH)is a global health problem that affects about 1%of the global population.Animal models of PH play a vital role in unraveling the pathophysiological mechanisms of the disease.The present study proposes a Kernel Extreme Learning Machine(KELM)model based on an improved Whale Optimization Algorithm(WOA)for predicting PH mouse models.The experimental results showed that the selected blood indicators,including Haemoglobin(HGB),Hematocrit(HCT),Mean,Platelet Volume(MPV),Platelet distribution width(PDW),and Platelet–Large Cell Ratio(P-LCR),were essential for identifying PH mouse models using the feature selection method proposed in this paper.Remarkably,the method achieved 100.0%accuracy and 100.0%specificity in classification,demonstrating that our method has great potential to be used for evaluating and identifying mouse PH models.
