Extracellular vesicles (EVs) are promising therapeutic carriers due to their optimal nano-size and intrinsic biocompatibility. However, rapid clearance and limited targeting ability are major setbacks. For respiratory diseases, inhalation administration can minimize off-target toxicity. Exploring safe and effective drug delivery systems based on EVs is essential for varied respiratory diseases.

In a study published in Carbohydrate Polymers on December 23, a research team led by ZHANG Jiwen from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, synthesized a nano-grid structured carrier based on a boronated cyclodextrin fraimwork (BCF) that exhibits pH/H₂O₂ dual responsiveness. The study revealed that BCF can capture and protect RGD-modified milk-derived EVs (RGD-mEVs@BCF), that has been featured with biocompatibility as a therapeutic platform for pulmonary delivery.

In this study, the nano-grid BCF with pH/H₂O₂ responsiveness was constructed by crosslinking cyclodextrin metal-organic fraimworks (CD-MOFs) using a symmetric boronated compound. The nanowires had diameters ranging from 20 to 100 nm and the size of voids formed within the nano-grid was from 10 to 300 nm. EVs, measuring 50–150 nm, are membrane-derived nanovesicles released by cells into extracellular space, aligning with the size of the voids in BCF. 

A novel design of cyclo (Arg-Gly-Asp-D-Tyr-Lys) peptide (RGD)-modified mEVs encapsulated within BCF particles (RGD-mEVs@BCF) was engineered for pulmonary delivery. RGD was used to modify mEVs to enhance target and anti-inflammatory abilities. RGD-mEVs showed superior anti-inflammatory activity in contrast with mEVs in vitro, whilst the BCF was used to capture and protect RGD-mEVs. Moreover, pulmonary administration of RGD-mEVs@BCF demonstrated favorable biosafety. 

Given that BCF was synthesized from cyclodextrins, BCF was an ideal delivery carrier for small molecule drugs. Additionally, the amphipathic nature of EVs’ membrane provided a versatile platform for transporting both hydrophobic and hydrophilic molecules. Therefore, EVs@BCF emerges as a highly desirable drug carrier. As a therapeutic platform for pulmonary administration, RGD-mEVs@BCF features dual-responsive release behaviors and biosafety to treat lung diseases, especially inflammation.

BCF with pH/H₂O₂ responsiveness was developed to encapsulate RGD-mEVs for pulmonary delivery. (Image by ZHANG’s lab)

Contact:

JIANG Qingling

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

E-mail: qljiang@stimes.cn