Chemical Communications · 2022 · 25 citations · 15 references
PharmacyMolecular PharmaceuticsPharmaceuticsCancer PharmacologyDrug DeliveryTargeted Drug DeliveryAntibody ConjugatesAntibody ConjugationAntibody-drug ConjugatesCancer Drug DeliveryPh-responsive Drug DeliveryTannin ChemistryAntibody-directed ProdrugsAntibody-drug Conjugate AntibodiesAntibody-drug Conjugate LinkersAntibody-drug Conjugate TherapyAntibody-drug LinkersPh DependencePh-responsive DeliveryPh-sensitive Linkers
We report a new 1-6 self-immolative, traceless crosslinker derived from the natural product gallic acid. The linker acts through a pH-dependent mechanism for drug release. This 5-(hydroxymethyl)pyrogallol orthoester derivative (HMPO) was stable for 24 hours at pH values of 7.4 and 6.6 and in plasma, releasing molecules bound to the hydroxymethyl moiety under acid-dependent stimuli at pH 5.5. The linker was non-toxic and was used for the conjugation of Doxorubicin (Doxo) or Combretastatin A4 with Cetuximab. The ADCs formed showed their pH responsivity reducing cell viability of A431 and A549 cancer cells better than Cetuximab alone.
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Acidity Generated by the Tumor Microenvironment Drives Local Invasion
Verónica Estrella, Tingan Chen, Mark C. Lloyd et al. · Cancer Research · 2013 · 1.4K citations · Full text
Medicine, Cancer Biology, Oncology +17
Samuele Cazzamalli, Alberto Dal Corso, Fontaine Widmayer et al. · Journal of the American Chemical Society · 2018 · 148 citations · Full text
Pharmacy, Oncology, Pharmacology +17