Target-activated cell/tissue-penetrating peptide for delivery of impermeable compounds and use thereof

A target-activated cell/tissue-penetrating peptide-drug conjugate for delivery of impermeable compounds, wherein said target-activated cell/tissue-penetrating peptide includes:

• a protein transduction domain (PTD), wherein the protein transduction domain (PTD) consists of D-type or L-type amino acids, and contains any one or more amino acids selected from the group consisting of arginine, lysine and histidine in an amount of 70-80%, wherein the protein transduction domain (PTD) is low molecular weight protamine (LMWP);
• a masking domain ionically bonded with the protein transduction domain (PTD), wherein the masking domain ionically bonded with the protein transduction domain (PTD) consists of D-type or L-type amino acids, and contains anionic amino acids in an amount of 70-100%, wherein the anionic amino acids include glutamic acid or aspartic acid, wherein the masking domain consists of 4-8 amino acids;
• and
• a spacer connecting the protein transduction domain (PTD) with the masking domain and having a cleavage site specific for a target cell/tissue enzyme, wherein the spacer has a site which is cleaved by matrix metalloprotease (MMP), wherein the spacer consists of SEQ ID NO:
• 25 (PLGLAG),
• wherein said target-activated cell/tissue-penetrating peptide-drug conjugate is prepared with a crosslinker selected from succinimidyl-4-[N-maleimidomethylcyclohexane-1-carboxy-[6-amidocaproate]] (SMCC) or its sulfonate (sulfo-SMCC).