Mahmoud Zaki El-Readi, Majed Abdurhman Abdulkarim, Ahmed A H Abdellatif, Mohamed E Elzubeir, Bassem Refaat, Mohammad Althubiti, Riyad Adnan Almaimani, Mohammed Hasan Mukhtar, Issa Saad Al-Moraya, Safaa Yehia Eid
{"title":"多柔比星-鞘氨醇纳米颗粒：乳腺癌细胞凋亡和细胞周期的制备与评估","authors":"Mahmoud Zaki El-Readi, Majed Abdurhman Abdulkarim, Ahmed A H Abdellatif, Mohamed E Elzubeir, Bassem Refaat, Mohammad Althubiti, Riyad Adnan Almaimani, Mohammed Hasan Mukhtar, Issa Saad Al-Moraya, Safaa Yehia Eid","doi":"10.1080/03639045.2024.2302557","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.</p><p><strong>Methods: </strong>Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).</p><p><strong>Results: </strong>Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC<sub>50</sub> = 1.4 μM) more than MCF-7/ADR cells (IC<sub>50</sub> = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC<sub>50</sub> = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC<sub>50</sub> = 7.2 μM) and SN (IC<sub>50</sub> = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC<sub>50</sub> from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC<sub>20</sub>) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.</p><p><strong>Conclusions: </strong>Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Doxorubicin-sanguinarine nanoparticles: formulation and evaluation of breast cancer cell apoptosis and cell cycle.\",\"authors\":\"Mahmoud Zaki El-Readi, Majed Abdurhman Abdulkarim, Ahmed A H Abdellatif, Mohamed E Elzubeir, Bassem Refaat, Mohammad Althubiti, Riyad Adnan Almaimani, Mohammed Hasan Mukhtar, Issa Saad Al-Moraya, Safaa Yehia Eid\",\"doi\":\"10.1080/03639045.2024.2302557\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.</p><p><strong>Methods: </strong>Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).</p><p><strong>Results: </strong>Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC<sub>50</sub> = 1.4 μM) more than MCF-7/ADR cells (IC<sub>50</sub> = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC<sub>50</sub> = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC<sub>50</sub> = 7.2 μM) and SN (IC<sub>50</sub> = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC<sub>50</sub> from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC<sub>20</sub>) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.</p><p><strong>Conclusions: </strong>Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.</p>\",\"PeriodicalId\":11263,\"journal\":{\"name\":\"Drug Development and Industrial Pharmacy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-01-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Development and Industrial Pharmacy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/03639045.2024.2302557\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development and Industrial Pharmacy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03639045.2024.2302557","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Doxorubicin-sanguinarine nanoparticles: formulation and evaluation of breast cancer cell apoptosis and cell cycle.
Background: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.
Methods: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).
Results: Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC50 = 1.4 μM) more than MCF-7/ADR cells (IC50 = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC50 = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC50 = 7.2 μM) and SN (IC50 = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC50 from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC20) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.
Conclusions: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.
期刊介绍：
The aim of Drug Development and Industrial Pharmacy is to publish novel, original, peer-reviewed research manuscripts within relevant topics and research methods related to pharmaceutical research and development, and industrial pharmacy. Research papers must be hypothesis driven and emphasize innovative breakthrough topics in pharmaceutics and drug delivery. The journal will also consider timely critical review papers.
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