Journal
CHEMICAL ENGINEERING JOURNAL
Volume 427, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.131742
Keywords
Sophorolipid assemblies-coated lipid-polymeric nanoparticle; Tumor microenvironment; Breast cancer metastasis; Gastrointestinal tract stability; Mucus penetration; Oral delivery
Categories
Funding
- National Natural Science Foundation of China [81773913, 81303232, 82074279]
- Natural Science Foundation of Shanghai [20ZR1458300]
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Oral delivery of therapeutic agents faces challenges in nanocarrier transfer in the gastrointestinal tract, overcoming physical stability, mucus penetration, and cellular uptake. Developing functional nanocarriers coated with microbial-derived sophorolipid assemblies shows promise in improving bioavailability and inhibiting breast cancer metastasis.
Oral delivery of therapeutic agents is complicated by issues associated with nanocarrier transfer in the gastrointestinal tract, such as physical stability, mucus penetration, and cellular uptake and transport. Various functional nanocarriers have been devised but more research is required to assure the desirable physical stability in the intestinal lumen and biology-responsive diffusion in the mucus. Here, we developed nanoparticles coated with microbial-derived sophorolipid assemblies for oral delivery of therapeutic agents, focusing on improved bioavailability and inhibition of breast cancer metastasis. Upon exposure to the intestinal lumen, the nanoparticles resisted changes in the pH and ion content, and retained their size and composition. They exhibited intestinal biologically responsive diffusion in the mucus because of a charge change from negative to nearly neutral, accompanied by a detachment of sophorolipid assemblies. The latter was possibly caused by the high sophorolipid affinity for mucin, which protected the nanoparticles during mucus penetration. The increased stability and enhanced mucus diffusion improved the intracellular uptake of nanoparticles, thus improving the oral bioavailability of the payload. Administration of silibinin and curcumin co-loaded nanoparticles resulted in an improved therapeutic effect of inhibiting breast cancer metastasis, by regulating tumor microenvironment, in 4T1 tumor bearing mice. The nanoparticles modulated epithelial-mesenchymal transition and inhibited angiogenesis. They also increased the infiltration of CD4(+) and CD8(+) T cells, and downregulated the immunosuppressive regulatory T cells and myeloid-derived suppressor cells in tumors. In conclusion, the novel nanocarriers are a promising oral drug delivery system.
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