Chen Zhipeng Nano Lett: Tumor-cell-surface adherable peptide-drug conjugate prodrug nanoparticles inhibit tumor metastasis

source：beike new material Views：4941time：2022-01-05 QQ Academic Group: 1092348845

Cancer metastasis is the main reason for the failure of chemotherapy. Inhibiting the activity of matrix metalloproteinases (MMPs) is a common strategy to reduce metastasis. However, broad-spectrum MMP inhibitors (MMPI) may cause undesirable side effects. In view of this, the Chen Zhipeng team of the School of Pharmacy, Nanjing University of Traditional Chinese Medicine screened a selective MMP2 inhibitor (CCKIGLFRWR) and connected it with doxorubicin (DOX) through a disulfide bond to produce an amphiphilic peptide-drug coupling(PDC).

The MPL shell exhibits a negative charge, which can prolong blood circulation. When the nanoparticles are passively targeted to the tumor site, the PDC core is exposed and realizes the charge conversion of the MPL shell. The PDC core can accumulate in the tumor matrix and adhere to the cell membrane. The disulfide bond between the MMPI peptide and DOX passes through Low concentration of glutathione mediates the reduction of tumor microenvironment and breaks down. DOX can effectively enter tumor cells and kill them. At the same time, the adhesion of MMPI peptides to the cell membrane can selectively inhibit the activity of MMP2 and achieve the effect of inhibiting tumor metastasis, which has great potential in the treatment of metastatic tumors.

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