Nanomedicine engulfed by macrophages for targeted tumor therapy

Abstract

Macrophages, exhibiting high intrinsic accumulation and infiltration into tumor tissues, are a novel drug vehicle for directional drug delivery. However, the low drug-loading (DL) capacity and the drug cytotoxicity to the cell vehicle have limited the application of macrophages in tumor therapy. In this study, different drugs involving small molecular and nanoparticle drugs were loaded into intrinsic macrophages to find a better way to overcome these limitations. Their DL capacity and cytotoxicity to the macrophages were first compared. Furthermore, their phagocytic ratio, dynamic distributions, and tumoricidal effects were also investigated. Results indicated that more lipid-soluble molecules and DL particles can be phagocytized by macrophages than hydrophilic ones. In addition, the N -succinyl- N ′-octyl chitosan (SOC) DL particles showed low cytotoxicity to the macrophage itself, while the dynamic biodistribution of macrophages engulfed with different particles/small molecules showed similar profiles, mainly excreted from liver to intestine pathway. Furthermore, macrophages loaded with SOC–paclitaxel (PTX) particles exhibited greater therapeutic efficacies than those of macrophages directly carrying small molecular drugs such as doxorubicin and PTX. Interestingly, macrophages displayed stronger targeting ability to the tumor site hypersecreting chemokine in immunocompetent mice in comparison to the tumor site secreting low levels of chemokine in immunodeficiency mice. Finally, results demonstrated that macrophages carrying SOC–PTX are a promising pharmaceutical preparation for tumor-targeted therapy.

Nanoparticle‐Laden Macrophages for Tumor‐Tropic Drug Delivery

“…and chemokines (e.g., CCL-5, 7, 8, 12, etc. ), [4–6] and navigate to the diseased sites, passing multiple biological barriers along the way. This holds true for central tumor areas, which are often avascular and inaccessible to conventional therapeutics.…”

“…injected macrophages to migrate to inflamed tissues. [6,24] We reason that if drug-loaded nanoparticles do not release the payloads in the early hours of cell entry, the adverse impacts can be held in check in spite of a high apparent drug content. This would buy time for macrophages to traffic to tumors, and release therapeutics in situ to induce efficient and selective cancer cell killing (Scheme 1).…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Controlled anticancer drug release [108,137] Tumor targeted therapy [138][139][140] Biomedical optical imaging [141] N-octyl-N-trimethyl chitosan Self-assembled polymeric micelles…”

A novel macrophage-mediated biomimetic delivery system with NIR-triggered release for prostate cancer therapy

“…Among the endogenous cells, macrophages have been reported as a tumor-targeted transport vector and attracted extensive research attention due to their strong phagocytic capacity and tolerance to chemotherapeutic drugs [6, 7]. Some studies have confirmed the feasibility of using macrophages to transport chemotherapeutic drugs or drug-loaded nanoparticles to the tumor site [8–11]. However, the low drug-loading capacity and insufficient drug release at the tumor site have limited the use of macrophages as a tumor targeting vector [12].…”