Lactoferrin-Modified Gambogic Acid Liposomes for Colorectal Cancer Treatment

Colorectal cancer (CRC) therapy is a big challenge, andseekingan effective and safe drug is a pressing clinical need. Gambogic acidis a potent antineoplastic agent without the drawback of bone marrowsuppression. To improve its druggability (e.g., poor water solubilityand tumor delivery), a lactoferrin-modified gambogic acid liposomaldelivery system (LF-lipo) was developed to enhance the treatment efficacyof CRC. The LF-lipo can specifically bind LRP-1 expressed on colorectalcancer cells to enhance drug delivery to the tumor cells and yieldenhanced therapeutic efficacy. The LF-lipo promoted tumor cell apoptosisand autophagy, reduced reactive oxygen species (ROS) levels in tumorcells, and inhibited angiogenesis; moreover, it could also repolarizetumor-associated macrophages from the M2 to M1 phenotype and induceICD to activate T cells, exhibiting the capability of remodeling thetumor immune microenvironment. The liposomal formulation yielded anefficient and safe treatment outcome and has potential for clinicaltranslation.