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Abstract
Marked release of MMAE in the tumour was detected when trastuzumab-SEC-MMAE and Phe-BF3 were injected into the same mouse (Fig. 1f). [...]our bioorthogonal system based on Phe-BF3 desilylation enables the controlled and efficient release of the drug from an antibody-drug conjugate. Owing to the loss of quenching by the nanoparticle18, the released GFP became fluorescent (Fig. 2b). [...]desilylation catalysed by Phe-BF3 can release a functional protein from nanoparticles in mammalian cells. The 4T1 tumours in control mice showed no mNeonGreen fluorescence; about 15% of cells in tumours injected with Phe-BF3 showed nuclear mNeonGreen signal (Fig. 2d, e, Extended Data Fig. 4i). [...]the PheBF3 desilylation system is compatible with nanoparticle-mediated delivery, and shows tumour selectivity. Transmission electron microscopy confirmed the uptake and cytosolic distribution of NP-GSDMA3 in 4T1 tumours (Extended Data Fig. 6e). [...]distributions of NP-GSDMA3 and Phe-BF3 also converged onto the tumour (Fig. 4a).