您的位置: 首页 > 2023年10月 第54卷 第10期 > 文字全文
2023年7月 第38卷 第7期11
目录

MMP-2响应的多肽修饰的PAMAM纳米颗粒负载DOX在乳腺癌细胞中的效应

Effects of MMP-2 responding peptide-modified PAMAM nanoparticles loaded with DOX in breast cancer cells

来源期刊: 广州医药 | 12-19 发布时间:2023-11-07 收稿时间:2025/11/13 18:29:50 阅读量:38
作者:
关键词:
尺寸可变纳米递送系统多肽肿瘤微环境响应
size-variablenano-delivery systempeptidetumor microenvironment response
DOI:
10.3969/j.issn.1000-8535.2023.10.002
收稿时间:
2023-05-04 
修订日期:
 
接收日期:
 
引用总数:
1  
目的 构建尺寸可变纳米递送系统PAMAM/DOX-pep并进行表征,检测其理化性质并评价其体外抗肿瘤效果与靶向性。方法 将阿霉素(DOX)物理包埋在阳离子聚合物PAMAM的疏水空腔内,以4-(N-马来酰亚胺基甲基)环己烷羧酸N-羟基琥珀酰亚胺酯(SMCC)作为交联剂,采用金属基质蛋白酶(MMP-2)敏感的多肽pep(CPLGVRGC)串联小粒径纳米颗粒形成大尺寸纳米递送系统(PAMAM/DOX-pep),对各纳米颗粒的粒径、电位、理化性质以及对小鼠乳腺癌细胞(4T1)的抑制作用、细胞摄取效果和核靶向作用进行检测。结果 PAMAM/DOX粒径约为10 nm,载药率为23%,多肽pep交联后形成的PAMAM/DOX-pep粒径约为200 nm,可在低pH下缓释DOX,7天内体外保持稳定且溶血率低、安全无毒,其与MMP-2共孵育后细胞摄取量与核靶向性显著增加。结论 尺寸可变纳米颗粒有助于克服尺寸所引发的递送障碍,将药物靶向递送至乳腺癌细胞核内并发挥作用,为纳米递送系统的设计提供了新策略。
Objective To construct and characterize the size-variable nano-delivery system PAMAM/DOX-pep,examine its physicochemical properties and evaluate its antitumor and targeting effects in vitro. Methods Small particle size PAMAM/DOX was obtained by physically encapsulating DOX within the hydrophobic cavity of the cationic polymer PAMAM. The large size nano-delivery system(PAMAM/DOX-pep)was formed by tandem linking small size nanoparticles by MMP-2 sensitive peptide pep(CPLGVRGC)using SMCC as a cross-linker. The particle size,potential,physical and chemical properties,inhibitory effect,cell uptake and nuclear targeting effect of each nanoparticle on mouse breast cancer cells(4T1)were detected. Results The particle size of PAMAM/DOX was about 10 nm,and the drug loading rate was 23%. PAMAMAM/DOX-pep,formed after cross-linking of peptide,had a particle size of about 200 nm,which could release DOX slowly at low pH,and remained stable,safe and non-toxic in vitro for 7 days with low hemolysis rate,and its cellular uptake amount and nuclear targeting rate increased significantly after co-incubation with MMP. Conclusions Size-variable nanoparticles overcome size-induced delivery barriers to target and deliver drugs to the 4T1 nucleus,providing a new strategy for the design of nano delivery systems.
1、 ZHANG M,FANG Z,CUI M,et al.Multifunctional metal complex-based gene delivery for tumour immune checkpoint blockade combination therapy[J].J Drug Target,2022,30(7):753-766. ZHANG M,FANG Z,CUI M,et al.Multifunctional metal complex-based gene delivery for tumour immune checkpoint blockade combination therapy[J].J Drug Target,2022,30(7):753-766.
2、 XIE Z,GUO W,GUO N,et al.Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy[J].Acta Biomater,2018(71):351-362. XIE Z,GUO W,GUO N,et al.Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy[J].Acta Biomater,2018(71):351-362.
3、 SHAHRIARI M,ZAHIRI M,ABNOUS K,et al.Enzyme responsive drug delivery systems in cancer treatment[J].J Control Release,2019(308):172-189. SHAHRIARI M,ZAHIRI M,ABNOUS K,et al.Enzyme responsive drug delivery systems in cancer treatment[J].J Control Release,2019(308):172-189.
4、 YAO Q,KOU L,TU Y,et al.MMP-RESPonsive 'Smart' drug delivery and tumor targeting[J].Trends Pharmacol Sci,2018,39(8):766-781. YAO Q,KOU L,TU Y,et al.MMP-RESPonsive 'Smart' drug delivery and tumor targeting[J].Trends Pharmacol Sci,2018,39(8):766-781.
5、 KHERALDINE H,RACHID O,HABIB A M,et al.Emerging innate biological properties of nano-drug delivery systems:A focus on PAMAM dendrimers and their clinical potential[J].Adv Drug Deliv Rev,2021(178):113908. KHERALDINE H,RACHID O,HABIB A M,et al.Emerging innate biological properties of nano-drug delivery systems:A focus on PAMAM dendrimers and their clinical potential[J].Adv Drug Deliv Rev,2021(178):113908.
6、 BAI S,ZHANG Y,LI D,et al.Gain an advantage from both sides:Smart size-shrinkable drug delivery nanosystems for high accumulation and deep penetration[J].Nano Today,2021(36):101038. BAI S,ZHANG Y,LI D,et al.Gain an advantage from both sides:Smart size-shrinkable drug delivery nanosystems for high accumulation and deep penetration[J].Nano Today,2021(36):101038.
7、 WANG Y,LI S,WANG X,et al.Smart transformable nanomedicines for cancer therapy[J].Biomaterials,2021(271):120737. WANG Y,LI S,WANG X,et al.Smart transformable nanomedicines for cancer therapy[J].Biomaterials,2021(271):120737.
8、 XU J,SONG M,FANG Z,et al.Applications and challenges of ultra-small particle size nanoparticles in tumor therapy[J].J Control Release,2022(353):699-712. XU J,SONG M,FANG Z,et al.Applications and challenges of ultra-small particle size nanoparticles in tumor therapy[J].J Control Release,2022(353):699-712.
9、 CHENG G,WU D,WANG S,et al.Stimuli-responsive size-changeable strategy for cancer theranostics[J].Nano Today,2021,38:101208. CHENG G,WU D,WANG S,et al.Stimuli-responsive size-changeable strategy for cancer theranostics[J].Nano Today,2021,38:101208.
10、 ZHANG M,GUO X,WANG M,et al.Tumor microenvironment-induced structure changing drug/gene delivery system for overcoming delivery-associated challenges[J].J Control Release,2020(323):203-224. ZHANG M,GUO X,WANG M,et al.Tumor microenvironment-induced structure changing drug/gene delivery system for overcoming delivery-associated challenges[J].J Control Release,2020(323):203-224.
11、 ZI Y,YANG K,HE J,et al.Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms[J].Adv Drug Deliv Rev,2022(188):114449. ZI Y,YANG K,HE J,et al.Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms[J].Adv Drug Deliv Rev,2022(188):114449.
12、 DOANE T L,BURDA C.The unique role of nanoparticles in nanomedicine:Imaging,drug delivery and therapy[J].Chem Soc Rev,2012,41(7):2885-911. DOANE T L,BURDA C.The unique role of nanoparticles in nanomedicine:Imaging,drug delivery and therapy[J].Chem Soc Rev,2012,41(7):2885-911.
1、李明.负载VEGF165-PE38的氮化硼纳米片的制备及其抗胶质母细胞瘤细胞活性研究[D].山西医科大学,2024.DOI:10.27288/d.cnki.gsxyu.2024.000364. 李明.负载VEGF165-PE38的氮化硼纳米片的制备及其抗胶质母细胞瘤细胞活性研究[D].山西医科大学,2024.DOI:10.27288/d.cnki.gsxyu.2024.000364.
上一篇
下一篇
出版者信息








《广州医药》公众号
目录