Polyphenols, as widely existing natural bioactive products, provide a vast array of advanced biomedical applications attributing to their potential health benefits that linked to antioxidant, anti-inflammatory, immunoregulatory, neuroprotective, cardioprotective function, etc. The polyphenol compounds could dynamically interact and bind with diverse species (such as polymers, metal ions, biomacromolecules, etc.) via multiple interactions, including hydrogen bond, hydrophobic, π–π, and cation–π interactions due to their unique chemical polyphenolic structures, providing far-ranging strategies for designing of polyphenol-based vehicles. Natural polyphenols emerged as multifaceted players, acting either as inherent therapeutics delivered to combat diverse diseases or as pivotal assemblies of drug delivery vehicles. In this review, we focused on the rational design and application of metal-phenolic network (MPN) based delivery systems, polyphenol-based coating films, polyphenol hollow capsules, polyphenol-incorporated hydrogels, and polymer-polyphenol-based nanoparticles (NPs) in various diseases therapeutic, including cancer, infection, cardiovascular disease, neurodegenerative disease, etc. Additionally. the versatility and mechanisms of polyphenols in the field of biomacromolecules (e.g., protein, peptide, nucleic acid, etc.) delivery and cell therapy have been comprehensively summarized. Going through the literature review, the remaining challenges of polyphenol-containing nanosystems need to be addressed are involved, including long-term stability, biosafety in vivo, feasibility of scale-up, etc., which may enlighten the further developments of this field. This review provides perspectives in utilizing natural polyphenol-based biomaterials to rationally design next generation versatile drug delivery system in the field of biomedicine, which eventually benefits public health.

The dramatic increase of microbial resistances against conventional available antibiotics is a huge challenge to the effective treatment of infectious disease and thus becoming a daunting global threat of major concern, which necessitates the development of innovative therapeutics. Nanomaterial-based antimicrobial strategies have emerged as novel and promising tools to combat lethal bacteria and recalcitrant biofilm, featuring the abilities to evade existing drug resistance-related mechanisms. In this review, recent advances in "state-of-the-art" nanosystems which acting either as inherent therapeutics or nanocarriers for the precise delivery of antibiotics, are comprehensively summarized. Those nanosystems can effectively accumulate at the infectious sites, achieve multifunctional synergistic antibacterial efficacy, and provide controlled release of antibiotics in response to endogenous or exogenous stimulus (e.g., low pH, enzymes, or illumination). Especially, the nanoplatform that integrated with photothermal/ photodynamic therapy (PTT/PDT) can enhance the bacterial destruction and biofilm penetration or ablation. In addition, nanoparticle- based approaches with enzymatically promoting bacterial killing, anti-virulence, and other mechanisms were also involved. Overall, this review provides crucial insights into the recent progress and remaining limitations of various antimicrobial nanotherapeutic strategies, and enlightens the further developments in this field simultaneously, which eventually benefiting public health.

Levodopa (L-DOPA), a precursor of dopamine, is commonly prescribed for the treatment of the Parkinson’s disease (PD). However, oral administration of levodopa results in a high level of homocysteine in the peripheral circulation, thereby elevating the risk of cardiovascular disease, and limiting its clinical application. Here, we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature. The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid (TA)/polyvinyl alcohol (PVA) via hydrogen bonding using the flash nanocomplexation (FNC) process, resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner. Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase, which indicate the dopaminergic neuron functions, were increased by 2- and 4-fold, respectively. Movement disorders and cerebral oxidative stress of the rats were significantly improved. This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs. This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.