Leveraging Nanodrug Delivery System for Simultaneously Targeting Tumor Cells and M2 Tumor-Associated Macrophages for Efficient Colon Cancer Therapy

Abstract

Tumor-associated macrophages (TAMs) widely exist in the solid tumors, which participate in the entire course of tumor development and execute momentous impacts. Therefore, manipulating TAMs has been identified as an expecting strategy with immense potential for cancer therapy. Herein, a nanodrug delivery system was leveraged for simultaneously targeting tumor cells and M2-type TAMs for efficient colon cancer therapy. The broad-spectrum anticancer chemotherapeutic drug doxorubicin (DOX) was hitchhiked in a mannose-modified bovine serum albumin (MAN-BSA) carrier. The DOX@MAN-BSA nanodrug delivery system was verified to possess feasible physical performances for unhindered systemic circulation and active targeting on colon tumors. DOX@MAN-BSA nanoparticles could be preferentially swallowed by colon tumor cells and M2 TAMs through mannose receptor-mediated endocytosis. Further in vivo antitumor therapy in CT26 colon tumor-bearing mice has achieved remarkable suppression efficacy with satisfactory biosafety. Leveraging the nanodrug delivery system for simultaneously targeting tumor cells and M2 TAMs has contributed a feasible strategy to collaboratively repress the malignant tumor cells and the collusive M2 TAMs for efficient cancer therapy.

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

“…A human antibody fragment, AbD15179, which is well characterized for its specificity for human CD44v6, an alternatively spliced CD44 isoform known to be overexpressed in 50% of colorectal cancers, was exploited for drug delivery in colon tumors [ 227 ]. Similarly, CD47 [ 228 ] and the mannose receptor (CD206) [ 229 , 230 ], overexpressed on the surface of colorectal carcinoma cells, were used as targets for the efficient targeting of colon cancer therapy.…”

“…Finally, instrumental modes can allow drugs to reach the gut, taking advantage of physical stimuli. In these cases, cues such as the magnetic or electric field, light, heat, or other forces can either move drugs to the gut or enable nanocarrier dissolution and drug release when they reach the desired site [ 229 , 230 , 253 , 254 ].…”

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors

“…A low M1/M2 ratio indicates poor prognosis and facilitates tumor cell metastasis [ 31 , 62 , 63 ]. Nanomaterials modulate TAM polarization [ [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] ], eliminate M2-type TAMs within tumor tissues [ 76 , 77 ], and enhance TAMs phagocytic capacity [ 78 , 79 ], thereby effectively impeding CRC progression ( Fig. 2 , Fig.…”

“…In addition to regulating TAM polarization, the utilization of nanomaterials to eliminate M2-type TAMs in CRC tissues serves as an effective approach to regulating TAM polarization [ 76 , 77 ] ( Fig. 3 ).…”

“…Additionally, humans have an enhanced uptake capacity for both TAMs and CRC cells [ 165 ]. Zeng et al synthesized DOX@MAN-BSA NPs, which are human-modified bovine serum albumin NPs that carry the chemotherapeutic drug doxorubicin (DOX) [ 76 ]. DOX@MAN-BSA NPs can concurrently eradicate M2-type TAMs and CRC cells expressing the mannose receptor [ 76 ].…”