Hydrogen peroxide is the most stable reactive oxygen species generated endogenously, participating in numerous physiological processes and abnormal pathological conditions. Mounting evidence suggests that a higher level of H2O2 exists in various disease conditions. Thus, H2O2 functions as an ideal target for site‐specific bioimaging and therapeutic targeting. The unique reactivity of organoborons with H2O2 provides a method for developing chemoselective molecules for biological and biomedical applications. This review highlights the design and application of boron‐derived molecules for H2O2 detection, and the utility of boron moieties toward masking reactive compounds leading to the development of metal prochelators and prodrugs for selectively delivering an active species at the target sites with elevated H2O2 levels. Additionally, the emergence of H2O2‐responsive theranostic agents consisting of both therapeutic and diagnostic moieties in one integrated system are discussed. The purpose of this review is to provide a better understanding of the role of boron‐derived molecules toward biological and pharmacological applications.

Triple-negative breast cancer (TNBC) has limited treatment options and the worst prognosis among all types of breast cancer. We describe two prodrugs, namely, CWB-20145 (1) and its methyl analogue FAN-NM-CH 3 (2) that reduced the size of TNBC-derived tumors. The DNA cross-linking of nitrogen mustard prodrugs 1 and 2 was superior to that of chlorambucil and melphalan once activated in the presence of H 2 O 2 . The cellular toxicity of 1 and 2 was demonstrated in seven human cancer cell lines. The TNBC cell line MDA-MB-468 was particularly sensitive toward 1 and 2. Compound 2 was 10 times more cytotoxic than chlorambucil and 16 times more active than melphalan. An evaluation of the gene expression demonstrated an upregulation of the tumor suppressor genes p53 and p21 supporting a transcriptional mechanism of a reduced tumor growth. Pharmacokinetic studies with 1 showed a rapid conversion of the prodrug. The introduction of a methyl group generated 2 with an increased half-life. An in vivo toxicity study in mice demonstrated that both prodrugs were less toxic than chlorambucil. Compounds 1 and 2 reduced tumor growth with an inhibition rate of more than 90% in athymic nude mice xenografted with MDA-MB-468 cells. Together, the in vivo investigations demonstrated that treatment with 1 and 2 suppressed tumor growth without affecting normal tissues in mice. These phenylboronic acid nitrogen mustard prodrugs represent promising drug candidates for the treatment of TNBC. However, the mechanisms underlying their superior in vivo activity and selectivity as well as the correlation between H 2 O 2 level and in vivo efficacy are not yet fully understood.