No abstract

Although cell-penetrating peptides (CPPs) has been proven to be efficient transporter for drug delivery, ideal peptide vectors for tumor therapy are still being urgently sought. Peptide antagonists have attracted substantial attention as targeting molecules because of their high tumor accumulation and antitumor activity compared with agonists. SPA, a derivative of substance P, is a potent antagonist that exhibits antitumor activity. Based on the amino acid composition of SPA, we speculate that it can translocate across cell membranes as CPPs do. In this study, our results demonstrated that SPA could enter cells similarly to a CPP. As a vector, SPA could efficiently deliver camptothecin and plasmids into cells. In addition, our results showed that SPA exhibited low toxicity to normal cells and high enzymatic stability. Taken together, our results validated the ability of SPA for efficient drug delivery. More importantly, our study opens a new avenue for designing ideal CPPs based on peptide antagonists.

No abstract

Camptothecin (CPT), a DNA‐toxin drug, exerts anticancer activity by inhibiting topoisomerase I. Targeted delivery of CPT into the cancer cell nucleus is important for enhancing its therapeutic efficiency. In this study, a new type of acid‐activated cell‐penetrating peptide (CPP) with nuclear localization capacity was constructed by conjugating six histidine residues and a hydrophobic peptide sequence, PFVYLI, to the nuclear localization sequence (NLS). Our results indicated that HNLS‐3 displayed significant pH‐dependent cellular uptake efficiency, endosomal escape ability, and nuclear localization activity. More importantly, the HNLS‐3–CPT conjugate showed obviously enhanced cytotoxicity and selectivity compared with CPT. Taken together, our findings provide an effective approach to develop efficient CPPs with both cancer‐ and nucleus‐targeting properties.

No abstract