The present invention discloses an intelligent responsive fusion polypeptide (HPVP-02) targeting HPV E6 / E7
protein and its application in the treatment of
cervical cancer. The
amino acid sequence of the polypeptide is shown in SEQ ID NO.1. It is composed of a dual-targeting module (specifically binding to HPV E6 / E7
protein), a pH response module (H5E5 sequence), an
immune activation module (PD-1 / PD-L1
inhibitory peptide) and a self-
assembly module (amphiphilic
nanostructure), and each module is connected in series through a flexible connecting
peptide. HPVP-02 responsively disassembles in the acidic microenvironment of the tumor, efficiently penetrates the
cell membrane, degrades E6 / E7
protein through the
ubiquitin-
proteasome pathway, restores the function of the host tumor
suppressor protein p53 / pRb, and simultaneously blocks the PD-1 / PD-L1 pathway to activate the anti-tumor immune response. The fusion polypeptide of the present invention has the advantages of targeting precision,
low toxicity and synergistic treatment, providing an innovative
treatment strategy for HPV-related tumors.