{"title":"透明质酸纳米凝胶与氯喹共同负载,通过溶酶体渗透和抑制食道来增强细胞内顺铂的递送。","authors":"Menghan Gao, Hong Deng, Yiyi Zhang, Huimin Wang, Runmeng Liu, Wei Hou, Weiqi Zhang","doi":"10.1016/j.carbpol.2023.121415","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Hyaluronan (HA) has been widely used to construct </span>nanocarriers<span> for cancer-targeted drug delivery, due to its excellent biocompatibility and intrinsic affinity towards CD44 that is overexpressed in most cancer types. However, the HA-based nanocarriers are prone to trapping in </span></span>lysosomes<span><span> following the HA-mediated endocytosis, which limited the delivered drug to access its pharmacological action sites and subsequently compromised the therapeutic efficacy. To overcome this intracellular obstacle, here we demonstrated the co-loading of </span>chloroquine<span> (CQ) in HA nanogel<span> could efficiently promote the intracellular delivery of cisplatin. The cisplatin coordination with HA generated the nanogel that could also co-encapsulate CQ (HA/Cis/CQ nanogel). Compared with cisplatin-loaded HA nanogel (HA/Cis), HA/Cis/CQ significantly promoted the lysosomal escape of cisplatin as well as enhanced tumor inhibition in the triple-negative breast cancer model. Mechanism studies suggested that co-delivery of CQ not only induced the lysosomal membrane permeabilization but also inhibited the lysophagy, which collectively contributed to the lysosomal instability and cisplatin escape. This HA/Cis/CQ nanogel elicited less toxicity compared with the combination of free Cis and CQ, thus suggesting a promising HA nanocarrier to boost the cisplatin delivery towards cancer-targeted therapy.</span></span></span></p></div>","PeriodicalId":261,"journal":{"name":"Carbohydrate Polymers","volume":null,"pages":null},"PeriodicalIF":10.7000,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyaluronan nanogel co-loaded with chloroquine to enhance intracellular cisplatin delivery through lysosomal permeabilization and lysophagy inhibition\",\"authors\":\"Menghan Gao, Hong Deng, Yiyi Zhang, Huimin Wang, Runmeng Liu, Wei Hou, Weiqi Zhang\",\"doi\":\"10.1016/j.carbpol.2023.121415\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Hyaluronan (HA) has been widely used to construct </span>nanocarriers<span> for cancer-targeted drug delivery, due to its excellent biocompatibility and intrinsic affinity towards CD44 that is overexpressed in most cancer types. However, the HA-based nanocarriers are prone to trapping in </span></span>lysosomes<span><span> following the HA-mediated endocytosis, which limited the delivered drug to access its pharmacological action sites and subsequently compromised the therapeutic efficacy. To overcome this intracellular obstacle, here we demonstrated the co-loading of </span>chloroquine<span> (CQ) in HA nanogel<span> could efficiently promote the intracellular delivery of cisplatin. The cisplatin coordination with HA generated the nanogel that could also co-encapsulate CQ (HA/Cis/CQ nanogel). Compared with cisplatin-loaded HA nanogel (HA/Cis), HA/Cis/CQ significantly promoted the lysosomal escape of cisplatin as well as enhanced tumor inhibition in the triple-negative breast cancer model. Mechanism studies suggested that co-delivery of CQ not only induced the lysosomal membrane permeabilization but also inhibited the lysophagy, which collectively contributed to the lysosomal instability and cisplatin escape. This HA/Cis/CQ nanogel elicited less toxicity compared with the combination of free Cis and CQ, thus suggesting a promising HA nanocarrier to boost the cisplatin delivery towards cancer-targeted therapy.</span></span></span></p></div>\",\"PeriodicalId\":261,\"journal\":{\"name\":\"Carbohydrate Polymers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2023-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Carbohydrate Polymers\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0144861723008809\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carbohydrate Polymers","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0144861723008809","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Hyaluronan nanogel co-loaded with chloroquine to enhance intracellular cisplatin delivery through lysosomal permeabilization and lysophagy inhibition
Hyaluronan (HA) has been widely used to construct nanocarriers for cancer-targeted drug delivery, due to its excellent biocompatibility and intrinsic affinity towards CD44 that is overexpressed in most cancer types. However, the HA-based nanocarriers are prone to trapping in lysosomes following the HA-mediated endocytosis, which limited the delivered drug to access its pharmacological action sites and subsequently compromised the therapeutic efficacy. To overcome this intracellular obstacle, here we demonstrated the co-loading of chloroquine (CQ) in HA nanogel could efficiently promote the intracellular delivery of cisplatin. The cisplatin coordination with HA generated the nanogel that could also co-encapsulate CQ (HA/Cis/CQ nanogel). Compared with cisplatin-loaded HA nanogel (HA/Cis), HA/Cis/CQ significantly promoted the lysosomal escape of cisplatin as well as enhanced tumor inhibition in the triple-negative breast cancer model. Mechanism studies suggested that co-delivery of CQ not only induced the lysosomal membrane permeabilization but also inhibited the lysophagy, which collectively contributed to the lysosomal instability and cisplatin escape. This HA/Cis/CQ nanogel elicited less toxicity compared with the combination of free Cis and CQ, thus suggesting a promising HA nanocarrier to boost the cisplatin delivery towards cancer-targeted therapy.
期刊介绍:
Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience.
The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.