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Design of smart polymeric therapeutics—We designed and synthesized trigger-responsive chain-shattering polymeric therapeutics (CSPTs) via condensation polymerization of a UV-or hydrogen peroxide-responsive domain and a bisfunctional drug as co-monomers. CSPTs have precisely controlled molecular composition and unique chain-shattering type of drug release mechanism. Drug release kinetics can be precisely controlled by means of the trigger treatment. Chemotherapeutic-containing CSPTs showed trigger-responsive in vitro and in vivo antitumor efficacy.