Mulberry Biomass-Derived Nanomedicines Mitigate Colitis through Improved Inflamed Mucosa Accumulation and Intestinal Microenvironment Modulation
Wenjing Yang,
Ya Ma,
Haiting Xu,
Zhenhua Zhu,
Jiaxue Wu,
Cheng Xu,
Wei Sun,
Erhu Zhao,
Min Wang,
Rui L. Reis,
Subhas C. Kundu,
Xiaoxiao Shi,
Bo Xiao
Affiliations
Wenjing Yang
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Ya Ma
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Haiting Xu
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Zhenhua Zhu
Department of Gastroenterology,
The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Jiaxue Wu
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Cheng Xu
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Wei Sun
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Erhu Zhao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Min Wang
Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Faculty of Materials and Energy,
Southwest University, Chongqing 400715, China.
Rui L. Reis
3Bs Research Group, I3Bs — Research Institute on Biomaterials, Biodegradables and Biomimetics,
University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco 4805-017, Guimaraes, Portugal.
Subhas C. Kundu
3Bs Research Group, I3Bs — Research Institute on Biomaterials, Biodegradables and Biomimetics,
University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco 4805-017, Guimaraes, Portugal.
Xiaoxiao Shi
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
Bo Xiao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences,
Southwest University, Chongqing 400715, China.
The therapeutic outcomes of conventional oral medications against ulcerative colitis (UC) are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment. Herein, a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs). The obtained FP127@RN-MLNs possessed exosome-like morphologies, desirable particle sizes (around 171.4 nm), and negatively charged surfaces (−14.8 mV). The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect. These MLNs could efficiently be internalized by colon epithelial cells and macrophages, reconstruct disrupted epithelial barriers, alleviate oxidative stress, provoke macrophage polarization to M2 phenotype, and down-regulate inflammatory responses. Importantly, in vivo studies based on chronic and acute UC mouse models demonstrated that oral administration of chitosan/alginate hydrogel-embedding FP127@RN-MLNs achieved substantially improved therapeutic efficacies compared with nonfluorinated MLNs and a first-line UC drug (dexamethasone), as evidenced by decreased colonic and systemic inflammation, integrated colonic tight junctions, and intestinal microbiota balance. This study brings new insights into the facile construction of a natural, versatile nanoplatform for oral treatment of UC without adverse effects.
