laminaran and Breast-Neoplasms

Laminarans are currently the focus of attention in regard to the selection of prospective agents for the prevention and treatment of cancer. Laminaran from Saccharina cichorioides was aminated to heighten anticancer and radiosensitizing activities and elucidate its molecular mode of action. Aminated laminaran, ScLNH

Topics: Amines; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Proliferation; Female; Glucans; Humans; In Vitro Techniques; Phaeophyceae; Radiation-Sensitizing Agents; Tumor Cells, Cultured

The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis. The downregulation of BMI-1 expression via small interfering RNA (siRNA) effectively inhibits tumor growth. However, the successful application of this therapy is limited by the unavailability of an appropriate vector for siRNA transfer. Therefore, this study aimed to construct a novel laminarin-based nonviral gene transfer vector to carry a constructed BMI-1-targeting siRNA and to investigate the in vitro and in vivo antitumor effects of this siRNA on breast cancer cells. To enhance the siRNA-carrying capacity, we introduced polyethylenimine (PEI) to laminarin's surface via N,N'-carbonyldiimidazole, which produced the cationic PEI-modified laminarin conjugate nLP. Subsequent in vitro experiments indicated that nLP not only formed a nanoparticle with a diameter of 200 nm through electrostatic interactions with siRNA but also showed high efficiency (95.0%) in the delivery siRNA to MCF-7 cells. The nanoparticle targeting BMI-1 (nLP/siBMI-2) reduced BMI-1 expression in breast MCF-7 cells by 90.9% reduction. An in vivo tumor suppression experiment demonstrated that the nLP/siBMI-2 nanoparticle had relatively low toxicity and good gene-therapeutic efficacy, with a tumor inhibition rate of 46.6%.

Topics: Animals; Breast Neoplasms; Female; Gene Transfer Techniques; Genetic Therapy; Glucans; Humans; MCF-7 Cells; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 7; Molecular Targeted Therapy; Nanoparticles; Polyethyleneimine; RNA, Small Interfering; Tissue Distribution; Xenograft Model Antitumor Assays

We fabricated a targeted delivery system for doxorubicin (Dox) using β-1,3-glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also functionalized with polyethylenimine (PEI) intended for increasing specific cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in place of a linker. Nanoparticles had spherical morphology with positive zeta potential. In-vitro cell viability assay on two breast cancer cell lines demonstrated acceptable toxicity against tested cell lines. Confocal microscopic images demonstrated the remarkable cytoplasmic uptake of the nanoparticles in Her2-overexpressing 4T1 cells. A controlled release of Dox from Glu-Dox nanoparticles was investigated. In-vivo studies were performed on female Balb/C mice. The volume of the induced tumors was calculated following intravenous administration of nanoparticles. The tumor volume diminished efficiently and more rapidly after administration of nanoparticles containing Dox. Based on survival results, the formulation of Dox targeted nanoparticles appeared very promising for the treatment of tumors. It could be concluded that Glu-Dox targeted nanoparticles have potential advantages for delivering anticancer drugs to the target tissue.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Drug Liberation; Female; MCF-7 Cells; Mice; Mice, Inbred BALB C; Nanoparticles; Polyethyleneimine; Receptor, ErbB-2; Succinates; Trastuzumab; Tumor Burden