Synthesis and Antitumor Activity of KFF Peptide-Drug Conjugates

In this article, to potentiate the antitumor efficacy of KFF, we designed a KFF-based peptide– drug conjugate. A KFF-camptothecin conjugate (KF-1) was synthesized via solid-phase synthesis, and its antitumor activity and mechanism were evaluated in HeLa and HepG2 cells using MTT assays and membrane lysis experiments. KFF exhibited inhibitory effects on both tumor cell lines, whereas conjugation with camptothecin significantly reduced IC50 values and increased antitumor activity by approximately fivefold. Membrane lysis experiments confirmed that KFF disrupted tumor cell membranes, and this mechanism was retained after conjugation. Collectively, the KFF-camptothecin conjugate substantially enhances antitumor efficacy, providing experimental evidence for the development of peptide–drug conjugates.