Self-Assembled Integrative Nutrient Carrier Platform Containing Green Tea Catechin for Short Bowel Syndrome Treatment.

Extensive resection of the small intestine leads to the development of short bowel syndrome (SBS), which reduces the effective absorptive surface area of the intestine and predisposes patients to emaciation, malnutrition, and other severe symptoms. Herein, green tea catechin (-)-epigallocatechin gallate (EGCG) and ferrous ions (Fe2+ ) are utilized to construct a nutrient carrier platform that self-assembles with nutrients to form phenolic-based nutrient complexes (PNCs). PNCs effectively prolong the residence and absorption time of nutrients in the intestine. Further this platform is applied to integrate full nutrient formula, an enteral nutrition (EN) preparation containing a range of full nutrient components. In an SBS rat model, the prepared phenolic-based integrative nutrient complexes (PINCs) enhance nutritional status, improve anemia and immune function, as well as facilitate the growth of remaining intestinal villi and crypts, and maintain the integrity of the intestinal barrier. In addition, PINCs enable the modulation of gut microbial dysbiosis, enrich the abundance of beneficial bacteria, and have no toxic effects after the long-term ingestion. These results provide a proof of principle for the use of polyphenol-based nanocomplexes as EN preparation, offering a feasible strategy for both nutritional support and therapeutic perspectives for SBS treatment.

Intratumoral synthesis of transformable metal-phenolic nanoaggregates with enhanced tumor penetration and retention for photothermal immunotherapy.

Rationale: Effective photothermal therapy (PTT) remains a great challenge due to the difficulties of delivering photothermal agents with both deep penetration and prolonged retention at tumor lesion spatiotemporally. Methods: Here, we report an intratumoral self-assembled nanostructured aggregate named FerH, composed of a natural polyphenol and a commercial iron supplement. FerH assemblies possess size-increasing dynamic kinetics as a pseudo-stepwise polymerization from discrete nanocomplexes to microscale aggregates. Results: The nanocomplex can penetrate deeply into solid tumors, followed by prolonged retention (> 6 days) due to the in vivo growth into nanoaggregates in the tumor microenvironment. FerH performs a targeting ablation of tumors with a high photothermal conversion efficiency (60.2%). Importantly, an enhanced immunotherapeutic effect on the distant tumor can be triggered when co-administrated with checkpoint-blockade PD-L1 antibody. Conclusions: Such a therapeutic approach by intratumoral synthesis of metal-phenolic nanoaggregates can be instructive to address the challenges associated with malignant tumors.