A drug delivery system targeting the tumour microenvironment produces outstanding therapeutic efficacy on triple-negative mammary and pancreatic models.

The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications.

The development of efficient protocols for cancer diagnosis remains highly challenging. An emerging approach relies on the detection in exhaled breath of volatile organic compounds (VOC) produced by tumours.I nt his context, described here is anovel strategy in whichaVOC-based probe is converted selectively in malignant tissues,b yatumourassociated enzyme,for releasing the corresponding VOC. The latter is then detected in the exhaled breath as atumour marker for cancer diagnosis.T his approach allows the detection of several different tumours in mice,t he monitoring of tumour growth and tumour response to chemotherapy. Thus,t he concept of "induced volatolomics" provides an ew way to explore biological processes using VOC-based probes that could be adapted to many biomedical applications.

Abioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology,w ed eveloped an ew generation of cleavable micelles able to disassemble through as equential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

The rise of chemical biology has led to the development of sophisticated molecular devices designed to explore and manipulate biological processes. Within this framework, we developed the first chemical system programmed for the selective internalization and subsequent enzyme-catalyzed double release of bioactive compounds inside a targeted population of cells. This system is composed of five distinct units including a targeting ligand, an enzymatic trigger, a self-immolative linker and two active compounds articulated around a chemical amplifier. Designed as such, this molecular assembly is capable in an autonomous manner to recognize a selected population of cells, penetrate into the intracellular medium through endocytosis and transform a single enzymatic activation step into the release of two active units. Demonstrating that an enzyme-catalyzed amplification process can occur spontaneously under the conditions prevailing within the cells could be an important step toward the development of innovative molecular systems for a diverse range of applications spanning drug delivery, biological sensors and diagnostics.

No abstract

Synthesis, in vitro and in vivo biological evaluations of a β-glucuronidase-responsive albumin-binding prodrug bearing a chemical amplifier.

Abioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology,w ed eveloped an ew generation of cleavable micelles able to disassemble through as equential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies. Conflict of interestTheauthors declare no conflict of interest.