{"title":"苯硼酸功能化聚乳酸-羟基乙酸纳米颗粒的开发，用于新型化疗-草药联合治疗肺癌：硅和体外概念验证。","authors":"Ankaj Kumar, Anshu Gupta, Anurag Saini, Sudhagar Selvaraju, Kalyan Kumar Sethi and Arvind Gulbake","doi":"10.1039/D5NR01407G","DOIUrl":null,"url":null,"abstract":"<p >This study includes a novel chemo-herbal combination using biochanin A (BCA) and lenvatinib (LTB) to synergize each other's anti-cancer activities. Phenylboronic acid (PBA)-functionalized poly (lactic-<em>co</em>-glycolic acid) (PLGA) was employed to specifically target the sialic acid overexpressed in lung cancer. ATR, DSC, and NMR studies confirmed the successful synthesis of PBA-PLGA, which was further utilized for the development of BCA and LTB co-loaded PBA-PLGA nanoparticles (PBA-PLGA-BCA-LTB NPs). A higher <em>in silico</em> docking score between LTB and different proteins of endothelial growth factor receptors (EGFRs) and a combination index value <1 supported the chemo-herbal combination regimen for lung cancer. In addition, the significantly higher protein expression (cle-PARP and cle-cas-3) from BCA-LTB explains the strong apoptotic effect. The optimized PBA-PLGA-BCA-LTB NPs exhibited a 182.2 ± 6.88 nm, 0.134 ± 0.074 polydispersity index, and −32.2 ± 3.40 mV zeta potential. ATR, DSC, and PXRD studies confirmed the amorphous dispersion of BCA-LTB in the PBA-PLGA matrix. A higher binding constant and rate coefficient, with a Δ<em>H</em> of −5.69 ± 0.183 (kcal mol<small><sup>−1</sup></small>), Δ<em>G</em> of −4.98 (kcal mol<small><sup>−1</sup></small>), and −<em>T</em>Δ<em>S</em> of 0.706 (kcal mol<small><sup>−1</sup></small>) using isothermal titration calorimetry (ITC) explained the enthalpy-driven specificity of PBA-PLGA towards sialic acid (Neu5AC). The prepared NPs showed physical stability at 4 ± 2 °C and were non-hemolytic and stable with plasma proteins. Significantly higher cytotoxicity and cellular uptake were observed for PBA-PLGA-BCA-LTB NPs in contrast to PLGA-BCA-LTB NPs and coarse-BCA-LTB. The PBA-PLGA-BCA-LTB NPs also exhibited anti-migration and invasion potential for A549 cells. <em>In vivo</em> pharmacokinetic studies indicated an increase in plasma half-life of the drugs and a decrease in hematological toxicities using PBA-PLGA-BCA-LTB NPs compared to free BCA-LTB. In summary, the PBA-PLGA-BCA-LTB NPs represent a biocompatible, potential, cancer-targeted, and effective treatment option for lung cancer treatment.</p>","PeriodicalId":92,"journal":{"name":"Nanoscale","volume":" 26","pages":" 15960-15987"},"PeriodicalIF":5.8000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development of phenylboronic acid functionalized poly (lactic-co-glycolic acid) nanoparticles for novel co-delivery of chemo-herbal combination towards lung cancer: an in silico and in vitro proof of concept†\",\"authors\":\"Ankaj Kumar, Anshu Gupta, Anurag Saini, Sudhagar Selvaraju, Kalyan Kumar Sethi and Arvind Gulbake\",\"doi\":\"10.1039/D5NR01407G\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >This study includes a novel chemo-herbal combination using biochanin A (BCA) and lenvatinib (LTB) to synergize each other's anti-cancer activities. Phenylboronic acid (PBA)-functionalized poly (lactic-<em>co</em>-glycolic acid) (PLGA) was employed to specifically target the sialic acid overexpressed in lung cancer. ATR, DSC, and NMR studies confirmed the successful synthesis of PBA-PLGA, which was further utilized for the development of BCA and LTB co-loaded PBA-PLGA nanoparticles (PBA-PLGA-BCA-LTB NPs). A higher <em>in silico</em> docking score between LTB and different proteins of endothelial growth factor receptors (EGFRs) and a combination index value <1 supported the chemo-herbal combination regimen for lung cancer. In addition, the significantly higher protein expression (cle-PARP and cle-cas-3) from BCA-LTB explains the strong apoptotic effect. The optimized PBA-PLGA-BCA-LTB NPs exhibited a 182.2 ± 6.88 nm, 0.134 ± 0.074 polydispersity index, and −32.2 ± 3.40 mV zeta potential. ATR, DSC, and PXRD studies confirmed the amorphous dispersion of BCA-LTB in the PBA-PLGA matrix. A higher binding constant and rate coefficient, with a Δ<em>H</em> of −5.69 ± 0.183 (kcal mol<small><sup>−1</sup></small>), Δ<em>G</em> of −4.98 (kcal mol<small><sup>−1</sup></small>), and −<em>T</em>Δ<em>S</em> of 0.706 (kcal mol<small><sup>−1</sup></small>) using isothermal titration calorimetry (ITC) explained the enthalpy-driven specificity of PBA-PLGA towards sialic acid (Neu5AC). The prepared NPs showed physical stability at 4 ± 2 °C and were non-hemolytic and stable with plasma proteins. Significantly higher cytotoxicity and cellular uptake were observed for PBA-PLGA-BCA-LTB NPs in contrast to PLGA-BCA-LTB NPs and coarse-BCA-LTB. The PBA-PLGA-BCA-LTB NPs also exhibited anti-migration and invasion potential for A549 cells. <em>In vivo</em> pharmacokinetic studies indicated an increase in plasma half-life of the drugs and a decrease in hematological toxicities using PBA-PLGA-BCA-LTB NPs compared to free BCA-LTB. In summary, the PBA-PLGA-BCA-LTB NPs represent a biocompatible, potential, cancer-targeted, and effective treatment option for lung cancer treatment.</p>\",\"PeriodicalId\":92,\"journal\":{\"name\":\"Nanoscale\",\"volume\":\" 26\",\"pages\":\" 15960-15987\"},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2025-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanoscale\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2025/nr/d5nr01407g\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanoscale","FirstCategoryId":"88","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2025/nr/d5nr01407g","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Development of phenylboronic acid functionalized poly (lactic-co-glycolic acid) nanoparticles for novel co-delivery of chemo-herbal combination towards lung cancer: an in silico and in vitro proof of concept†
This study includes a novel chemo-herbal combination using biochanin A (BCA) and lenvatinib (LTB) to synergize each other's anti-cancer activities. Phenylboronic acid (PBA)-functionalized poly (lactic-co-glycolic acid) (PLGA) was employed to specifically target the sialic acid overexpressed in lung cancer. ATR, DSC, and NMR studies confirmed the successful synthesis of PBA-PLGA, which was further utilized for the development of BCA and LTB co-loaded PBA-PLGA nanoparticles (PBA-PLGA-BCA-LTB NPs). A higher in silico docking score between LTB and different proteins of endothelial growth factor receptors (EGFRs) and a combination index value <1 supported the chemo-herbal combination regimen for lung cancer. In addition, the significantly higher protein expression (cle-PARP and cle-cas-3) from BCA-LTB explains the strong apoptotic effect. The optimized PBA-PLGA-BCA-LTB NPs exhibited a 182.2 ± 6.88 nm, 0.134 ± 0.074 polydispersity index, and −32.2 ± 3.40 mV zeta potential. ATR, DSC, and PXRD studies confirmed the amorphous dispersion of BCA-LTB in the PBA-PLGA matrix. A higher binding constant and rate coefficient, with a ΔH of −5.69 ± 0.183 (kcal mol−1), ΔG of −4.98 (kcal mol−1), and −TΔS of 0.706 (kcal mol−1) using isothermal titration calorimetry (ITC) explained the enthalpy-driven specificity of PBA-PLGA towards sialic acid (Neu5AC). The prepared NPs showed physical stability at 4 ± 2 °C and were non-hemolytic and stable with plasma proteins. Significantly higher cytotoxicity and cellular uptake were observed for PBA-PLGA-BCA-LTB NPs in contrast to PLGA-BCA-LTB NPs and coarse-BCA-LTB. The PBA-PLGA-BCA-LTB NPs also exhibited anti-migration and invasion potential for A549 cells. In vivo pharmacokinetic studies indicated an increase in plasma half-life of the drugs and a decrease in hematological toxicities using PBA-PLGA-BCA-LTB NPs compared to free BCA-LTB. In summary, the PBA-PLGA-BCA-LTB NPs represent a biocompatible, potential, cancer-targeted, and effective treatment option for lung cancer treatment.
期刊介绍：
Nanoscale is a high-impact international journal, publishing high-quality research across nanoscience and nanotechnology. Nanoscale publishes a full mix of research articles on experimental and theoretical work, including reviews, communications, and full papers.Highly interdisciplinary, this journal appeals to scientists, researchers and professionals interested in nanoscience and nanotechnology, quantum materials and quantum technology, including the areas of physics, chemistry, biology, medicine, materials, energy/environment, information technology, detection science, healthcare and drug discovery, and electronics.
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