Novel oral pH-responsive dual-targeted nanogels for precision therapy of colorectal cancer.

Colorectal cancer (CRC) chemotherapy faces challenges such as poor gastrointestinal stability, low targeting efficiency, severe toxicity, and complex protocols. Recent pH-responsive nanocarriers mainly improve environmental stability but lack intelligent control. This study introduces a novel two-step "one-pot" aqueous synthesis strategy to create dual-targeting core-shell nanoparticles (LTDR-DS NPs) that are both efficient and environmentally friendly. The core contains a lysine-tannic acid conjugate and D-galactose, while the shell is a pH-responsive dopamine-alginate sodium (DA-SA) "smart armor". This design enables spatiotemporal targeting, combining pH responsiveness, precise delivery, and multi-mechanistic synergy. Unlike traditional nanocarriers, LTDR-DS NPs co-optimize stability and targeting, overcoming the dual challenges of poor stability and low targeting efficiency. They offer a groundbreaking, low-toxicity treatment strategy with high potential for clinical translation, enhancing therapeutic efficacy while reducing systemic toxicity and advancing CRC chemotherapy.