{"title":"Self-assembly of Antisense DNA-Camptothecin Amphiphile into Glutathione-Responsive Nanoparticles for Combination Cancer Therapy.","authors":"Anusree Krishna, Anupama Babulal, Mareena Sajeev, Nidhin Ravi, Gowtham Raj, Anitta Antony, Nikhil Dev Narendradev, Srinivasa Murty Srinivasula, Reji Varghese","doi":"10.1002/chem.202404068","DOIUrl":null,"url":null,"abstract":"<p><p>Recent years have witnessed the rapid growth of combination therapy for the treatment of cancer. Chemo and antisense DNA therapies are two clinically proven and efficient treatment modalities for cancer. However, direct delivery of both chemo and antisense oligonucleotides into the cancerous cells is challenging and hence there is a high demand for the development of new strategies that permit the direct delivery of chemo and antisense therapeutic agents in a targeted fashion. Herein, we show a supramolecular approach for the direct delivery of hydrophobic chemo drug and cell impermeable antisense oligonucleotide into a cancer cell in a targeted fashion. Synthesis of an amphiphile (DNA1-CPT) consist of hydrophobic camptothecin (CPT) conjugated to an antisense oligonucleotide (DNA1) via glutathione-responsive disulphide linker is reported. Self-assembly of DNA1-CPT results in the formation of GSH-responsive NPs with CPT as the hydrophobic core and DNA1 as the hydrophilic shell. Self-assembled NPs exhibits excellent cellular internalization via endocytosis pathway, and the high concentration of glutathione inside the cancer cells causes the cleavage of disulphide bond of the NPs and trigger the simultaneous release of CPT and DNA1a. Enhanced cytotoxicity is observed for the NPs due to the synergetic combination of chemo and antisense DNA therapies.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":" ","pages":"e202404068"},"PeriodicalIF":3.9000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry - A European Journal","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/chem.202404068","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Recent years have witnessed the rapid growth of combination therapy for the treatment of cancer. Chemo and antisense DNA therapies are two clinically proven and efficient treatment modalities for cancer. However, direct delivery of both chemo and antisense oligonucleotides into the cancerous cells is challenging and hence there is a high demand for the development of new strategies that permit the direct delivery of chemo and antisense therapeutic agents in a targeted fashion. Herein, we show a supramolecular approach for the direct delivery of hydrophobic chemo drug and cell impermeable antisense oligonucleotide into a cancer cell in a targeted fashion. Synthesis of an amphiphile (DNA1-CPT) consist of hydrophobic camptothecin (CPT) conjugated to an antisense oligonucleotide (DNA1) via glutathione-responsive disulphide linker is reported. Self-assembly of DNA1-CPT results in the formation of GSH-responsive NPs with CPT as the hydrophobic core and DNA1 as the hydrophilic shell. Self-assembled NPs exhibits excellent cellular internalization via endocytosis pathway, and the high concentration of glutathione inside the cancer cells causes the cleavage of disulphide bond of the NPs and trigger the simultaneous release of CPT and DNA1a. Enhanced cytotoxicity is observed for the NPs due to the synergetic combination of chemo and antisense DNA therapies.
期刊介绍:
Chemistry—A European Journal is a truly international journal with top quality contributions (2018 ISI Impact Factor: 5.16). It publishes a wide range of outstanding Reviews, Minireviews, Concepts, Full Papers, and Communications from all areas of chemistry and related fields.
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Chemistry—A European Journal is published on behalf of ChemPubSoc Europe, a group of 16 national chemical societies from within Europe, and supported by the Asian Chemical Editorial Societies. The ChemPubSoc Europe family comprises: Angewandte Chemie, Chemistry—A European Journal, European Journal of Organic Chemistry, European Journal of Inorganic Chemistry, ChemPhysChem, ChemBioChem, ChemMedChem, ChemCatChem, ChemSusChem, ChemPlusChem, ChemElectroChem, and ChemistryOpen.