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.

Massive attack: Galactoside prodrugs have been designed that can be selectively activated by lysosomal β-galactosidase located inside cancer cells expressing a specific tumor-associated receptor. This efficient enzymatic process triggers a potent cytotoxic effect, releasing the potent antimitotic agent MMAE and allowing the destruction of both receptor-positive and surrounding receptor-negative tumor cells.

Ring of protection: A [2]rotaxane 1 protects and selectively releases a bioactive pentapeptide. The rotaxane macrocycle provides a defensive shield that very significantly improves the poor stability of the peptide to both individual peptidases and the cocktail of enzymes present in human plasma. Glycosidase‐catalyzed cleavage of a carbohydrate ‘stopper’ in the rotaxane triggers release of the parent peptide (see picture).

The kinetics of decomposition of the pharmaceutical ranitidine (a major precursor of NDMA) during chloramination was investigated and some decomposition byproducts were identified by using high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The reaction between monochloramine and ranitidine followed second order kinetics and was acid-catalyzed. Decomposition of ranitidine formed different byproducts depending on the applied monochloramine concentration. Most identified products were chlorinated and hydroxylated analogues of ranitidine. In excess of monochloramine, nucleophilic substitution between ranitidine and monochloramine led to byproducts that are critical intermediates involved in the formation of NDMA, for example, a carbocation formed from the decomposition of the methylfuran moiety of ranitidine. A complete mechanism is proposed to explain the high formation yield of NDMA from chloramination of ranitidine. These results are of great importance to understand the formation of NDMA by chloramination of tertiary amines.

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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.

A new antibody-drug conjugate (ADC) chemical drug-linker platform based on polysarcosine enables increased drug-loading, improved pharmacokinetics and exquisite in vivo potency.