Hyaluronic‐Acid‐Presenting Self‐Assembled Nanoparticles Transform a Hyaluronidase HYAL1 Substrate into an Efficient and Selective Inhibitor

Abstract

In this study, an original method of macromolecular design was used to develop a hyaluronidase‐1 (HYAL1) inhibitor from its principal substrate, hyaluronic acid (HA). HA‐based nanoparticles (HA‐NP) were obtained by copolymer self‐assembly and their effects on HYAL1 activity were investigated by combining different analytical tools. Compared to HA, HA‐NP exhibited an enhanced stability against HYAL1 degradation while maintaining its interaction with the HA receptors CD44 and aggrecan. HA‐NP displayed a strong and selective inhibition of HYAL1 activity and retarded the hydrolysis of higher‐molar‐mass HA in solution. A co‐nanoprecipitation process was used to formulate a range of hybrid nanoparticle samples, which demonstrated the specificity and efficiency of HA‐NP in HYAL1 inhibition.

A porphyrin-based metallacage for enhanced photodynamic therapy

“…HAase is a class of proteolytic enzymes that can effectively break down HA leading to increased drug penetration. [35][36][37][38] Meantime, HAase can also reduce the IFP, promote angiogenesis, increase blood flow and greatly alleviate hypoxia. [39][40][41][42][43] Here, we constructed a platform and achieved an enhanced PDT treatment.…”

Dual Gate‐Controlled Therapeutics for Overcoming Bacterium‐Induced Drug Resistance and Potentiating Cancer Immunotherapy

“…Then, methoxy-poly(ethylene glycol) 113 -block-poly(L-glutamic acid sodium salt) 200 (PEG-PLE), Gem, and Cip solutions were sequentially added into OSiND suspension to obtain drug-loaded nanoreservoirs (Gem/Cip@SiPNG). Dynamic light scattering results showed that the nanoreservoirs with an OSiND/PEG-PLE/Gem/Cip weight ratio of 8:1:2:2had afavorable hydrodynamic size of 61.4 AE 19.6 nm (which is suitable for drug delivery) and al ow polydispersity index of 0.102 (Table S1), and were thus selected for further use.T oe ndow the nanoreservoirs with active tumor-targeting ability,HAwhich can recognize cancer cells [14] was used to encapsulate the nanoreservoirs to form Gem/Cip@SiPNG@HA. Thez eta potential of Gem/Cip@SiPNG@HAd ecreased with the increasing HA solution volumes at the beginning and then remained stable when the HA solution volume reached 200 mL( Figure S3).…”

Nanostructured particles assembled from natural building blocks for advanced therapies

“…10b). 183 This makes HA suitable for active tumor targeting delivery. 184,185 For example, HA-polyethyleneimine This journal is © The Royal Society of Chemistry 2022 nanoparticles encapsulating microRNA-125b can be used to target peritoneal macrophages, which internalize the HA nanoparticles and then migrate to macrophage-ablated lung tissues.…”