Rational Design of Bioinspired Lipoprotein System to Improve Penetration in Colorectal Peritoneal Metastases

Chemotherapy of lethal colorectal peritoneal metastases (PM) is notoriously challenged by poor drug delivery efficiency in PM tumors. Inspired by the histopathological examinations of PM tumors from colon cancer patients, a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system was optimized from 8 formulations with profound penetrating ability in PM tumors of colorectal cancers. Then, a chemotherapeutic 7-ethyl-10-hydroxy-camptothecin (SN38)-loaded R-BLP (termed SR-BLP) was designed to promote their penetration in PM tumors and improve the chemotherapeutic efficacy. In CT26-induced PM models, SR-BLP exhibited better penetration profiles in PM tumors over a counterpart liposomal formulation. SR-BLP treatment produced an 80.03% suppression of PM incidence with obvious DNA damage and topoisomerase I (TOP I) downregulation and caused a 1.78-fold prolongation of survival time. Therefore, the histopathological features-inspired R-BLP provides an encouraging tumor-penetrating delivery platform for the effective chemotherapy of colorectal PM.