Enhancing the Antitumor Efficacy of Zwitterionic Peptide-Based Nanoscale Micelles through Sensitizing Their Response in Solid Tumors
Enhancing the Antitumor Efficacy of Zwitterionic Peptide-Based Nanoscale Micelles through Sensitizing Their Response in Solid Tumors
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DOI：
10.1021/acsanm.2c03880
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发表时间：
2022-11
影响因子：
5.9
通讯作者：
Xinyue Wei;Z. Xiang;Weili Xue;Shengfu Chen
中科院分区：
文献类型：
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作者：
Xinyue Wei;Z. Xiang;Weili Xue;Shengfu Chen
Although nanodelivery has made unprecedented progress in enhancing the efficacy of chemotherapeutic drugs, there is still much room for improvement. Zwitterionic nanodrugs have great potential to be a universal platform for nanodelivery because of the exceptional hemocompatibility and ultralow immunogenicity, although they are sensitive to the tumor microenvironment (TME) for tumor cell targeting and internalization. Here, a negatively biased zwitterionic peptide micelle, a mimic of albumin, was developed to improve two vital factors, which are the responsive transition of stability and affinity to tumor cells from circulation to the slightly acidic TME. The incorporation of positively charged hydrophobic phenformin into the camptothecin (CPT)-conjugated micelles (Pep-SSetc-CPT@Phen) can make the micelles more compact to reduce premature drug release in circulation while improving the sensitivity of the micelles to MCF-7-xenografted tumors by tuning their zeta potential in the TME. Thus, Pep-SSetc-CPT@Phen exhibited more tumor-preferred biodistribution and longer blood circulation than nonphenformin-incorporated micelles (Pep-SSetc-CPT), thereby enhancing tumor growth inhibition with lower side effects. Together, these results have provided a promising combinational method to enhance the transition of stability and the sensitivity to the TME for developing biomimetic zwitterionic nanodrugs with high antitumor efficacy.
