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

Abstract

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.

Mussel-Inspired PEDOT-Incorporated Gelatin-Based Conductive Hydrogel with Flexibility and Electroactivity to Accelerate Wound Healing In Vitro

“…With the incorporation of PDA, the Gel-PDA/PEDOT hydrogel exhibited outstanding cell affinity and enhanced cell attachment and proliferation. L929 cells, being a kind of mouse skin fibroblast cell, have always been widely used in in vitro cell experiments to investigate the effect of conductive hydrogels on wound healing due to their advantages of a stable proliferation rate and simple culture conditions. , L929 cells were cocultured with extract solutions from various hydrogels to evaluate their cytotoxicity through Live/Dead staining and CCK-8 assays. , As shown in Figure a, a large number of L929 cells with spindle-shaped morphologies could be observed in the control and Gel hydrogel groups after 3 days of incubation. However, few L929 cells appeared in the Gel-PEDOT hydrogel groups due to the limited cytotoxicity of PEDOT. , In sharp contrast, in the Gel-PDA/PEDOT hydrogel groups, large numbers of cells presented a well-spreading shape, mainly due to the presence of PEDOT.…”

“…43,44 L929 cells were cocultured with extract solutions from various hydrogels to evaluate their cytotoxicity through Live/Dead staining and CCK-8 assays. 45,46 As shown in Figure 6a, a large number of L929 cells with spindle-shaped morphologies could be observed in the control and Gel hydrogel groups after 3 days of incubation. However, few L929 cells appeared in the Gel-PEDOT hydrogel groups due to the limited cytotoxicity of PEDOT.…”

Cell-Targeted Metal-Phenolic Nanoalgaecide in Hydroponic Cultivation to Enhance Food Sustainability

“…32 Raman spectroscopy confirmed the coordination with a Cu−O vibration at 857−472 cm −1 in the low-frequency region (Figure S4). 24 UV−vis spectroscopy of CuBes showed a significant decrease and shifted from 279 to 274 nm after BWT coordination with Cu 2+ ions (Figure S5). Due to the insolubility of CuBes in deuterated reagents, we have conducted a simulated testing to demonstrate the successful synthesis of CuBes by nuclear magnetic resonance (NMR) measurement.…”

“…Natural polyphenols are the main constituents of biomass and can be obtained from all plants on earth . Owing to their multiple interactions (including hydrophobic interactions, hydrogen bonding, and π–π interactions), natural polyphenols are bioderived versatile “green” building blocks that enable the engineering of multifunctional supramolecular materials which offer the means to generate strong interfacial forces to drive the cell targeting. − Additionally, nanoenabled phenolic materials have been greatly explored in biotechnology and nanomedicine, − due to their biocompatibility and modular compositions. , Herein, we developed self-assembled nanoalgaecides comprising natural polyphenols and functional copper ions (Cu 2+ ions), referred to as CuBes. CuBes are capable of attaching on the surface of algal cells directed by a phenolic-mediated interfacial interaction and achieve sustained release of Cu 2+ ions specifically around the localized cellular microenvironment (Figure B).…”

Emerging Self‐Assembled Nanoparticles Constructed from Natural Polyphenols for Intestinal Diseases

“…The resulting PNPs can deeply enter solid tumors and exhibit a long retention time over 6 days. [ 54 ] After NIR irradiation, FerH can achieve targeted tumor ablation with photothermal conversion efficiencies up to 60.2%, which possess a higher light–heat conversion efficiency compared to the previously reported MPN‐based photothermal nanosystems.…”