摘要
Current antibody–drug conjugates(ADCs)suffer from low tissue penetration and significant side effects,largely due to the permanent linkage and/or premature release of cytotoxic payloads.Herein,we developed a prodrug–antibody conjugate(ProADC)strategy by conjugating a bioorthogonal-activatable prodrug with an antibody that allowed on-target release and on-demand activation of cytotoxic drugs at a tumor site.The bioorthogonal-caged prodrug exhibited an enhanced permeability into and on-demand activation within cancer cells,while the pH-sensitive ADC linker allowed on-target release of the anticancer agent.Together,the ProADCs showed enhanced tumor penetration and alleviated side effects for use as an on-target and on-demand chemotherapy agents.
