期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 122, 期 -, 页码 1100-1114出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2018.09.059
关键词
Cancer; Cell cycle arrest; Mitochondrial disruption; Tumor associated macrophages; Th1 immune response
资金
- Council of Scientific and Industrial Research, New Delhi, India under CSIR network project [CSC0302]
- Indian Council of Medical Research, New Delhi, India
- Council of Scientific and Industrial Research, New Delhi, India
- Department of Science and Technology, New Delhi, India
Immunotherapeutic nanoparticles (NPs) could be a viable option for delivering cytotoxic agents in a manner which suppresses their toxic manifestations. Doxorubicin (DOX) loaded NPs were prepared using fucoidan (FCD), an immunomodulatory polysaccharide and evaluated against cancer. FCD was electrostatically assembled with cationic polyethylenimine (PEI) through intermolecular electrostatic interactions to develop an immunomodulatory platform to deliver DOX. FCD NPs offered improved cytotoxicity (2.64 folds), cell cycle arrest in G1-S phase (34.65%) and apoptosis (66.12%) in tumor cells compared to free DOX. The enhanced apoptosis was due to raised mitochondrial depolarization (88.00%). In vivo anticancer activity in 4T1 induced tumor bearing BALB/c mice demonstrated a 2.95 folds enhanced efficacy of NPs. Importantly, NPs treatment generated an immunotherapeutic response indicated by gradual increment of the plasma IL-12 levels and reversed polarization of tumor associated macrophages (TAMs) towards M1 subtype. Furthermore, pharmacokinetic study suggested that NPs administration in tumor infested mice caused serum DOX levels to vary in a biphasic pattern, with twin peaks occurring at 1 h and 6 h which help in maintaining preferential drug localization in tumor. Developed NPs would be an excellent approach for improved immune-chemotherapy (in terms of efficacy, safety and immunocompetency) against cancer. (C) 2018 Elsevier B.V. All rights reserved.
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