title: Exploiting macrophages as targeted carrier to guide nanoparticles into glioma.
abstract: The restriction of anti-cancer drugs entry to tumor sites in the brain is a major impediment to the development of new strategies for the treatment of glioma. Based on the finding that macrophages possess an intrinsic homing property enabling them to migrate to tumor sites across the endothelial barriers in response to the excretion of cytokines/chemokines in the diseased tissues, we exploited macrophages as 'Trojan horses' to carry drug-loading nanoparticles (NPs), pass through barriers, and offload them into brain tumor sites. Anticancer drugs were encapsulated in nanoparticles to avoid their damage to the cells. Drug loading NPs was then incubated with RAW264.7 cells in vitro to prepare macrophage-NPs (M-NPs). The release of NPs from M-NPs was very slow in medium of DMEM and 10% FBS and significantly accelerated when LPS and IFN-γ were added to mimic tumor inflammation microenvironment. The viability of macrophages was not affected when the concentration of doxorubicin lower than 25 μg/ml. The improvement of cellular uptake and penetration into the core of glioma spheroids of M-NPs compared with NPs was verified in in vitro studies. The tumor-targeting efficiency of NPs was also significantly enhanced after loading into macrophages in nude mice bearing intracranial U87 glioma. Our results provided great potential of macrophages as an active biocarrier to deliver anticancer drugs to the tumor sites in the brain and improve therapeutic effects of glioma.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Pang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Han
authors.affiliation: Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D018874:Spheroids, Cellular / Q000187:drug effects; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D004317:Doxorubicin; D007371:Interferon-gamma
keywords: glioma; hypoxic; inflammation; macrophages; nanoparticles