Asif Mohd Itoo, Milan Paul, Naitik Jain, Varshini Are, Ankita Singh, Balaram Ghosh, Swati Biswas
{"title":"生物素化铂(IV)共轭氧化石墨烯纳米粒子用于乳腺癌的靶向化疗-光热联合疗法。","authors":"Asif Mohd Itoo, Milan Paul, Naitik Jain, Varshini Are, Ankita Singh, Balaram Ghosh, Swati Biswas","doi":"10.1016/j.bioadv.2024.214121","DOIUrl":null,"url":null,"abstract":"<div><div>Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(<em>OX</em>)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both <em>in vitro</em> and <em>in vivo</em> conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(<em>OX</em>)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(<em>OX</em>)PEG (1/1/0.2) NPs (±L), and GO(<em>OX</em>)PB (1/1/0.2) NPs (−L). The <em>in vivo</em> therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(<em>OX</em>)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(<em>OX</em>)PB (1/1/0.2) NPs. The developed nanoplatform, in this context, may serve as a potential nanomedicine to address conventional nephrotoxicity in breast cancer and prevent metastasis by combining chemo-photothermal therapy.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"168 ","pages":"Article 214121"},"PeriodicalIF":5.5000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer\",\"authors\":\"Asif Mohd Itoo, Milan Paul, Naitik Jain, Varshini Are, Ankita Singh, Balaram Ghosh, Swati Biswas\",\"doi\":\"10.1016/j.bioadv.2024.214121\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(<em>OX</em>)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both <em>in vitro</em> and <em>in vivo</em> conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(<em>OX</em>)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(<em>OX</em>)PEG (1/1/0.2) NPs (±L), and GO(<em>OX</em>)PB (1/1/0.2) NPs (−L). The <em>in vivo</em> therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(<em>OX</em>)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(<em>OX</em>)PB (1/1/0.2) NPs. 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Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer
Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(OX)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both in vitro and in vivo conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(OX)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(OX)PEG (1/1/0.2) NPs (±L), and GO(OX)PB (1/1/0.2) NPs (−L). The in vivo therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(OX)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(OX)PB (1/1/0.2) NPs. The developed nanoplatform, in this context, may serve as a potential nanomedicine to address conventional nephrotoxicity in breast cancer and prevent metastasis by combining chemo-photothermal therapy.
期刊介绍:
Biomaterials Advances, previously known as Materials Science and Engineering: C-Materials for Biological Applications (P-ISSN: 0928-4931, E-ISSN: 1873-0191). Includes topics at the interface of the biomedical sciences and materials engineering. These topics include:
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