Nanomedicine engulfed by macrophages for targeted tumor therapy.
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.
Department of Biomedical Engineering, China Pharmaceutical University.
Siwen
S
Li
Department of Biomedical Engineering, China Pharmaceutical University.
Song
S
Feng
Department of Biomedical Engineering, China Pharmaceutical University.
Li
L
Ding
Department of Biomedical Engineering, China Pharmaceutical University.
Yuxi
Y
Liu
Department of Biomedical Engineering, China Pharmaceutical University.
Qiuyun
Q
Zhu
Department of Biomedical Engineering, School of Automation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People's Republic of China.
Zhiyu
Z
Qian
Department of Biomedical Engineering, China Pharmaceutical University.
Yueqing
Y
Gu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D061986:MCF-7 Cells; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage; D000067996:RAW 264.7 Cells; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D018925:Chemokines; D004337:Drug Carriers; D008055:Lipids; D008823:Micelles; C118639:N-succinyl-chitosan; D004317:Doxorubicin; D048271:Chitosan; D017239:Paclitaxel
SOC–PTX; drug-loading capacity; macrophage; tumor-targeted therapy