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Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

ABSTRACT: To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice.

SUBMITTER: Amano C

PROVIDER: S-EPMC4567266 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

Amano Chie C Minematsu Hideki H Fujita Kazuyo K Iwashita Shinki S Adachi Masaki M Igarashi Koichi K Hinuma Shuji S

PloS one 20150911 9

To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticl ...[more]

PMID: 26361331

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Project description:Ionizing radiation (IR) is an essential component of therapy for alveolar rhabdomyosarcoma. Nuclear factor-kappaB (NF-??) transcription factors are upregulated by IR and have been implicated in radioresistance. We evaluated the ability of curcumin, a putative NF-?? inhibitor, and cells expressing genetic NF- ?? inhibitors (I?B? and p100 super-repressor constructs) to function as a radiosensitizer. Ionizing radiation induced NF-?? activity in the ARMS cells in vitro in a dose- and time-dependent manner, and upregulated expression of NF-?? target proteins. Pretreatment of the cells with curcumin inhibited radiation-induced NF-?? activity and target protein expression. In vivo, the combination of curcumin and IR had synergistic antitumor activity against Rh30 and Rh41 ARMS xenografts. The greatest effect occurred when tumor-bearing mice were treated with curcumin prior to IR. Immunohistochemistry revealed that combination therapy significantly decreased tumor cell proliferation and endothelial cell count, and increased tumor cell apoptosis. Stable expression of the super-repressor, SR-I?B?, that blocks the classical NF-?B pathway, increased sensitivity to IR, while expression of SR-p100, that blocks the alternative pathway, did not. Our results demonstrate that curcumin can potentiate the antitumor activity of IR in ARMS xenografts by suppressing a classical NF-?? activation pathway induced by ionizing radiation. These data support testing of curcumin as a radiosensitizer for the clinical treatment of alveolar rhabdomyosarcoma. IMPACT OF WORK: The NF-?? protein complex has been linked to radioresistance in several cancers. In this study, we have demonstrated that inhibiting radiation-induced NF-?? activity by either pharmacologic (curcumin) or genetic (SR-I?B?) means significantly enhanced the efficacy of radiation therapy in the treatment of alveolar rhabdomyosarcoma cells and xenografts. These data suggest that preventing the radiation-induced activation of the NF-?? pathway is a promising way to improve the antitumor efficacy of ionizing radiation and warrants clinical trials.

Project description:Breast cancer is one of the most prevalent types of malignant tumors in the world, resulting in a high incidence of death. The development of new molecules and technologies aiming to apply more effective and safer therapy strategies has been intensively explored to overcome this situation. The association of nanoparticles with known antitumor compounds (including plant-derived molecules such as curcumin) has been considered an effective approach to enhance tumor growth suppression and reduce adverse effects. Therefore, the objective of this systematic review was to summarize published data regarding evaluations about efficacy and toxicity of curcumin nanoparticles (Cur-NPs) in in vivo models of breast cancer. The search was carried out in the databases: CINAHL, Cochrane, LILACS, Embase, FSTA, MEDLINE, ProQuest, BSV regional portal, PubMed, ScienceDirect, Scopus, and Web of Science. Studies that evaluated tumor growth in in vivo models of breast cancer and showed outcomes related to Cur-NP treatment (without association with other antitumor molecules) were included. Of the 528 initially gathered studies, 26 met the inclusion criteria. These studies showed that a wide variety of NP platforms have been used to deliver curcumin (e.g., micelles, polymeric, lipid-based, metallic). Attachment of poly(ethylene glycol) chains (PEG) and active targeting moieties were also evaluated. Cur-NPs significantly reduced tumor volume/weight, inhibited cancer cell proliferation, and increased tumor apoptosis and necrosis. Decreases in cancer stem cell population and angiogenesis were also reported. All the studies that evaluated toxicity considered Cur-NP treatment to be safe regarding hematological/biochemical markers, damage to major organs, and/or weight loss. These effects were observed in different in vivo models of breast cancer (e.g., estrogen receptor-positive, triple-negative, chemically induced) showing better outcomes when compared to treatments with free curcumin or negative controls. This systematic review supports the proposal that Cur-NP is an effective and safe therapeutic approach in in vivo models of breast cancer, reinforcing the currently available evidence that it should be further analyzed in clinical trials for breast cancer treatments.

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Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

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Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

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