In:
Biomaterials Science, Royal Society of Chemistry (RSC), Vol. 11, No. 15 ( 2023), p. 5195-5204
Abstract:
Tumor-active-targeting drugs such as antibody–drug conjugates have emerged as promising accurate therapeutic agents. However, their complex preparations risk compromising the targeting ability of the fragment antigen binding (Fab) region and promote aggregation over long-term storage. Here, we propose a tumor-active-targeting nanomedicine, aPDL1–PLG–MMAE, that effectively targets programmed death-ligand 1 (PDL1) high-expressing tumors and delivers monomethyl auristatin E (MMAE). aPDL1–PLG–MMAE consists of an anti-PDL1 monoclonal antibody (aPDL1) and poly( l -glutamic acid) (PLG) grafted Fc-III-4C peptide/Val–Cit–PAB–MMAE (Fc–PLG–MMAE). Fc–PLG–MMAE was obtained by conjugating the Fc-III-4C peptide and Val–Cit–PAB–MMAE to PLG via amide condensation. The strong affinity between the fragment crystallizable (Fc) region of aPDL1 and the Fc-III-4C peptide enabled aPDL1 and Fc–PLG–MMAE to self-assemble into aPDL1–PLG–MMAE after four hours of coincubation in PBS. As this nanomedicine can be quickly prepared for immediate use, the required antibodies can be stored separately from the Fc–PLG–MMAE portion for extended periods, which also facilitates transport. Moreover, aPDL1–PLG–MMAE demonstrated robust tumor recognition and targeting effects on MC38 colon cancer cells, resulting in potent therapeutic efficacy without significant toxicities.
Type of Medium:
Online Resource
ISSN:
2047-4830
,
2047-4849
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2023
detail.hit.zdb_id:
2714251-6
detail.hit.zdb_id:
2693928-9
