Biomimetically constructing a hypoxia-activated programmable phototheranostics at the molecular level.

The hypoxic microenvironment is considered the preponderant initiator to trigger a cascade of progression and metastasis of tumors, also being the major obstacle for oxygen consumption therapeutics, including photodynamic therapy (PDT). In this work, we report a programmable strategy at the molecular level to modulate the reciprocal interplay between tumor hypoxia, angiogenesis, and PDT outcomes by reinforcing synergistic action between a H2O2 scavenger, O2 generator and photosensitizer. The modular combination of a catalase biomimetic (tri-manganese cryptand, 1) and a photosensitizer (Ce6) allowed the rational design of a cascade reaction beginning with dismutation of H2O2 to O2 under hypoxic conditions to enhance photosensitization and finally photooxidation. Concurrently, this led to the decreased expression of the vascular endothelial growth factor (VEGF) and effectively reduced unwanted growth of blood vessels observed in the chick chorioallantois membrane (CAM). Notably, the proof-of-principle experiments using the tumor-bearing models proved successful in enhancing PDT efficacy, prolonging their life cycles, and improving immunity, which could be monitored by magnetic resonance imaging (MRI).

Porpholactone Chemistry: Shining New Light on an Old Cofactor.

Invited for this month's cover is the group of Jun-Long Zhang, Peking University, Beijing. The cover picture shows the porpholactone cofactor, which play unique roles in molecular imaging and therapy (or theranostics), catalysis, as well as energy and optical materials. This class of molecules is ideal for more intriguing scientific research and future practical applications. Read the full text of the Minireview at 10.1002/cplu.202000494.

Porpholactone Chemistry: Shining New Light on an Old Cofactor.

The emergence of porpholactone chemistry, discovered over 30 years ago, has significantly stimulated the development of biomimetic tetrapyrrole chemistry. It offers an opportunity, through modifications of non-pyrrolic building blocks, to clarify the relationship between chemical structure and excited-state properties, deciphering the structural code for the biological functions of life pigments. With intriguing photophysical properties in the red to near-infrared (NIR) regions, facile modulation of their electronic nature by fine-tuning chemical structures, and coordination ability with diverse metal ions, these novel porphyrinoids have favorable prospects in the fields of optical materials, bioimaging and therapy, and catalysis. In this Minireview, we summarize the brief history of porpholactone chemistry, and focus on the studies carried out in our group, particularly on the regioisomeric effect, NIR lanthanide luminescence, and metal catalysis. We outline the perspectives of these compounds in the construction of porpholactone-related biomedical applications and optical and energy materials, in order to inspire more interest and further advance bioinspired inorganic chemistry and lanthanide chemical biology.