A magnetic resonance imaging-guided drug delivery system for premetastatic niche theranostics and colorectal cancer liver metastasis intervention

Colorectal cancer liver metastasis (CRLM) poses a major challenge in cancer theranostics, in which hepatic stellate cell (HSC) activation participates in fibrosis progression and colorectal cancer (CRC) cell recruitment, catalyzing the formation of fibrosis-concomitant premetastatic niche (PMN). Targeting the crosstalk between activated HSCs (aHSCs) and CRC cells, we develop a bioengineered, mesoporous superparamagnetic iron oxide nanoparticle (mSPIONP)-based theranostic nano-system (mSPIONP-Cur@eCM). Camouflaged with CXC chemokine receptor type 4 (CXCR4)-overexpressing CRC cytomembranes, this nano-system exhibits a dual PMN-targeting function, exerting a homologous recognition to CRC cells and anchors to aHSCs with a high secretion of stromal cell-derived factor-1 (SDF-1). Its mSPIONP-Cur core affords not only T2-weighted magnetic resonance imaging (MRI) but also curcumin (Cur) delivery, initiating liver fibrosis detection and metastasis foci delineation, simultaneously blocking the HSC-CRC cell crosstalk by amplifying Cur's therapeutic effect. Verified in fibrosis and CRLM models, mSPIONP-Cur@eCM exhibits great potential for suppressing the fibrosis-concomitant PMN and intervening the CRLM progression.