International Journal of Nanomedicine (Jul 2020)
Chiral Active β-Glucan Nanoparticles for Synergistic Delivery of Doxorubicin and Immune Potentiation
Abstract
Jintao Huang,1,* Chaoxi Wu,2,* Shunqing Tang,3 Pengjun Zhou,2 Jianping Deng,1 Zhen Zhang,1 Yifei Wang,2 Zhiping Wang1 1Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510632, People’s Republic of China; 2Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People’s Republic of China; 3Biomedical Engineering Institute, Jinan University, Guangzhou 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yifei Wang; Zhiping Wang Email [email protected]; [email protected]: β-glucans are chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability of its chiral feature. However, the exploitation of chiral properties of these nanoparticles in drug delivery systems was seldom conducted.Methods: β-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. In a conformation transition process, these β-glucan molecules were then self-assembled with anti-cancer drug doxorubicin into nanoparticles to construct drug delivery systems. The chiral interactions between the drug and carriers were revealed by circular dichroism spectra, ultraviolet and visible spectrum, fourier transform infrared spectroscopy, dynamic light scattering and transmission electron microscope. The immune-potentiation properties of modified β-glucan nanoparticles were evaluated by analysis of the mRNA expression in RAW264.7 cell model. Further, the antitumor efficacy of the nanoparticles against the human breast cancer were studied in MCF-7 cell model by cellular uptake and cytotoxicity experiments.Results: β-glucan nanoparticles can activate macrophages to produce immune enhancing cytokines (IL-1β, IL-6, TNF-α, IFN-γ). A special chirality of the carriers in diameter of 50∼ 160 nm can also associate with higher drug loading ability of 13.9% ∼ 38.2% and pH-sensitive release with a change of pH from 7.4 to 5.0. Cellular uptake and cytotoxicity experiments also prove that the chiral-active β-glucan nanoparticles can be used in anti-cancer nanomedicine.Conclusion: This work demonstrates that β-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.Keywords: β-glucan, chiral, nanoparticles, doxorubicin, anti-cancer, drug delivery systems, immune-potentiation
