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.

Keywords:

• macrophage
• drug-loading capacity
• SOC–PTX
• tumor-targeted therapy

Supplementary materials

Figure S1 The drug loading and release characteristics of macrophages and SOC-PTX.

Notes: (A) Drug loading rate of macrophage with SOC-PTX and PTX. (B) PTX release from SOC-PTX in different pH solutions. Abbreviations: PTX, paclitaxel; SOC, N-succinyl-N′-octyl chitosan.

Figure S2 The drug transportation between macrophages and MDA-MB-231 cells.

Notes: (A) Drugs/nanoparticles delivery from macrophages to tumor cells observed under a laser confocal microscope. Mean fluorescence intensity of MDA-MB-231 tumor cells (B) and macrophages (C).

Abbreviations: DIC, differential interference contrast microscope; SOC, N-succinyl-N′-octyl chitosan.

Acknowledgments

The authors are grateful to Natural Science Foundation Committee of China (NSFC 81220108012, 61335007, 81371684, 81000666, 81171395, and 81328012) for their financial support. Siwen Li and Song Feng were regarded as co-first authors.

Disclosure

The authors report no conflicts of interest in this work.