Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence Imaging, and Magnetic Resonance Imaging

In this paper, we report synthesis and characterization of a novel multimodality (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly­(<i>N</i>-(2-hydroxypropyl)­methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd–DOTA complex). The polymer was characterized using UV–vis absorption spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell lines shows the polymer’s ability to be internalized in the cells. The transverse relaxation time (<i>T</i>₂) of the polymer was observed to be pH-dependent, whereas the spin-lattice relaxation time (<i>T</i>₁) was not. The pH probe in the polymer shows a strong fluorescence-based ratiometric pH response with emission window changes, exhibiting blue emission under acidic conditions and green emission under basic conditions, respectively. This study provides new materials with multimodalities for pH sensing and imaging

Salutaxel, a Conjugate of Docetaxel and a Muramyl Dipeptide (MDP) Analogue, Acts as Multifunctional Prodrug That Inhibits Tumor Growth and Metastasis

Salutaxel (<b>3</b>) is a conjugate of docetaxel (<b>7</b>) and a muramyl dipeptide (MDP) analogue. Docetaxel (<b>7</b>) has been recognized as a highly active chemotherapeutic agent against various cancers. MDP and its analogues are powerful potentiators of the antitumor actions of various tumor-necrotizing agents. This article documents the discovery of compound <b>3</b> and presents pharmacological proof of its biological function in tumor-bearing mice. Drug candidate <b>3</b> was superior to compound <b>7</b> in its ability to prevent tumor growth and metastasis. Compound <b>3</b> suppressed myeloid-derived suppressor cell (MDSC) accumulation in the spleens of tumor-bearing mice and decreased various serum inflammatory cytokines levels. Furthermore, compound <b>3</b> antagonized the nucleotide-binding oligomerization domain-like receptor 1 (NOD1) signaling pathway both in vitro and in vivo