AbstractIn order to prevent drugs from being captured and degraded by the acidic environment of organelles, such as lysosomes, after entering cells, this study designed and synthesized a novel carrier amphiphilic polypeptide (DGRHHHLLLAAAA), designated P13, for use as a tumor-targeting drug delivery vehicle. The P13 peptide was synthesized 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 value of about 0.000 21 g l−1, and the particle size of P13-Dox nanospheres was 167 nm. 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−1 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 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.
