Redox and pH Dual-Responsive Polypeptide Micelles for Doxorubicin Delivery with Enhanced Anticancer Efficacy AITranslate
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Herein, redox and pH dual-responsive poly(glutamic acid) micelle-encapsulated doxorubicin (DOX) was developed in this report. First, methoxy poly(ethylene glycol)-block-poly(glutamic acid) (PEG-SS-PG) linked by a disulfide bond was synthesized through ring-opening polymerization of l-glutamic acid γ-benzyl ester carboxyanhydride using terminal aminosylated poly(ethylene glycol) (PEG-SS-NH2) as an initiator. After that, PEG-SS-PG was assembled with doxorubicin (DOX) by a simple mixing to form tight PEG-SS-PG/DOX micelles by virtue of the electrostatic interaction between carboxylic acid groups of PEG-SS-PG and amine groups of DOX. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) characterization indicated that the micelles have a spherical structure with an average particle size of about 70 nm. The drug loading efficiency (DLE) was measured to be 92.3 wt %. The release behavior of PEG-SS-PG/DOX was checked in the presence of glutathione (GSH) and different pH. The results showed that about 90% DOX was released within 36 h under the combined action of high GSH concentration and low pH, while less than 25% DOX was released at pH 7.4 in the absence of GSH. These data confirmed the glutathione and pH dual-responsiveness of PEG-SS-PG/DOX micelles. The micelles could be internalized by cancer cells, as revealed by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). The pharmacokinetics and biodistribution of the PEG-SS-PG/DOX micelles were further investigated in detail. Compared with free DOX, PEG-SS-PG/DOX micelles improved the biodistribution of DOX and prolonged blood circulation time. Finally, in vivo antitumor efficacy was studied using 4T1 breast tumor-bearing BALB/c mice. It was found that the tumor inhibition rate of PEG-SS-PG/DOX was up to 86.32%, indicating greatly effective antitumor performance. Taken together, PEG-SS-PG micelles can encapsulate DOX via electrostatic interaction to form tight micelles and possess redox and pH dual-responsive release of DOX and highly effective inhibition of tumor growth, which have potential application for the treatment of tumors.
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DOI：https://doi.org/10.1021/acsapm.3c00371
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Herein, redox and pH dual-responsive poly(glutamic acid) micelle-encapsulated doxorubicin (DOX) was developed in this report. First, methoxy poly(ethylene glycol)-block-poly(glutamic acid) (PEG-SS-PG) linked by a disulfide bond was synthesized through ring-opening polymerization of l-glutamic acid γ-benzyl ester carboxyanhydride using terminal aminosylated poly(ethylene glycol) (PEG-SS-NH2) as an initiator. After that, PEG-SS-PG was assembled with doxorubicin (DOX) by a simple mixing to form tight PEG-SS-PG/DOX micelles by virtue of the electrostatic interaction between carboxylic acid groups of PEG-SS-PG and amine groups of DOX. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) characterization indicated that the micelles have a spherical structure with an average particle size of about 70 nm. The drug loading efficiency (DLE) was measured to be 92.3 wt %. The release behavior of PEG-SS-PG/DOX was checked in the presence of glutathione (GSH) and different pH. The results showed that about 90% DOX was released within 36 h under the combined action of high GSH concentration and low pH, while less than 25% DOX was released at pH 7.4 in the absence of GSH. These data confirmed the glutathione and pH dual-responsiveness of PEG-SS-PG/DOX micelles. The micelles could be internalized by cancer cells, as revealed by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). The pharmacokinetics and biodistribution of the PEG-SS-PG/DOX micelles were further investigated in detail. Compared with free DOX, PEG-SS-PG/DOX micelles improved the biodistribution of DOX and prolonged blood circulation time. Finally, in vivo antitumor efficacy was studied using 4T1 breast tumor-bearing BALB/c mice. It was found that the tumor inhibition rate of PEG-SS-PG/DOX was up to 86.32%, indicating greatly effective antitumor performance. Taken together, PEG-SS-PG micelles can encapsulate DOX via electrostatic interaction to form tight micelles and possess redox and pH dual-responsive release of DOX and highly effective inhibition of tumor growth, which have potential application for the treatment of tumors.
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| GB/T 7714-2015 | [1] Hanlei Xing, Yanhao Zhang, Ji Wang, et al. ACS Applied Polymer Materials, 2023(5). DOI:10.1021/acsapm.3c00371. |
| MLA | [1] Hanlei Xing, et al., ACS Applied Polymer Materials, no. 5, 2023, https://doi.org/10.1021/acsapm.3c00371. |
| APA | [1] Hanlei Xing, Yanhao Zhang, Ji Wang, Chao Liu, Wenhui Zha, Yang Wang, Shuo Dong, & Xinsong Li. (2023). ACS Applied Polymer Materials(5). https://doi.org/10.1021/acsapm.3c00371 |
| IEEE | [1] Hanlei Xing, Yanhao Zhang, Ji Wang, Chao Liu, Wenhui Zha, Yang Wang, Shuo Dong, and Xinsong Li, ACS Applied Polymer Materials, no. 5, 2023, doi: 10.1021/acsapm.3c00371. keywords: {polypeptide micelle;dualresponsiveness;doxorubicin;electrostatic interaction;antitumor activity} |