Preparation of an amphiphilic peptide (P13) with proton sponge effect and analysis of its antitumor activity

Abstract

In order to prevent drugs from being captured and degraded by the acidic environment of organelles, this study designed and prepared a novel carrier amphiphilic polypeptide (DGRHHHLLLAAAA), designated P13, for use as a tumor-targeting drug delivery vehicle.The P13 peptide was prepared by the solid phase synthesis method, and its self-assembly behavior and drug-loading capacity in aqueous solution were studied and characterized in vitro. Doxorubicin (DOX) was loaded by dialysis method, and P13 and DOX were mixed at a mass ratio of 6:1 to form regular rounded globules. The acid-base buffering capacity of P13 was investigated determined by acid-base titration. The results revealed that P13 had excellent acid-base buffering capacity, a critical micelle concentration (CMC) value of about 0.00021g/L, and the particle size of P13-DOX nanospheres was 167 nm, and the zeta potentials of P13-DOX was 24.8 ± 1.0 mV. The drug encapsulation efficiency and drug loading capacity of micelles were 20.40±1.21% and 21.25±2.79%, respectively. At the concentration of 50 μg/mL of P13-DOX , the inhibition rate was 73.35%. The results of the in vivo antitumor activity assay in mice showed that P13-DOX also exhibited excellent inhibitory effect on tumor growth, compared with the tumor weight of 1.1 g in the control group, the tumor weight in the P13-DOX-treated group was only 0.26 g. Additionally, the results of hematoxylin and eosin (H&E) staining of the organs showed that P13-DOX had no damaging effect on normal tissues. The novel amphiphilic peptide P13 with proton sponge effect designed and prepared in this study is expected to be a promising tumor-targeting drug carrier with excellent application potential.

Biomembrane-wrapped gene delivery nanoparticles for cancer therapy

“…There are three principal methods of endosome/lysosome escape: i) reduces the stability of the lysosome membrane by electrostatic action. Both cationic liposomes and cationic polymers exhibit the ability to induce endosome/lysosome rupture and nucleic acid molecule release ( Wu et al, 2023 ). ii) disturbs the stability of lysosomes by changing pH.…”