Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(28), С. 36063 - 36076

Опубликована: Июль 3, 2024

The cell membrane separates the intracellular compartment from extracellular environment, constraining exogenous molecules to enter cell. Conventional electroporation typically employs high-voltage and short-duration pulses facilitate transmembrane transport of impermeable under natural conditions by creating temporary hydrophilic pores on membrane. Electroporation not only enables entry but also directs distribution electric field. Recent advancements have markedly enhanced efficiency molecule delivery, achieved through utilization microstructures, microelectrodes, surface modifications. However, little attention is paid regulating motion during after passing improve delivery efficiency, resulting in an unsatisfactory high dose demand. Here, we proposed strategy charged process progressive (PEP), utilizing modulated fields. Efficient with expanded increased accumulation PEP was demonstrated numerical simulations experimental results. demand can be reduced 10–40% depending size charge molecules. We confirmed safety for both short long terms cytotoxicity assays transcriptome analysis. Overall, this work reveals mechanism effectiveness PEP-enhanced suggests potential integration field manipulation molecular modification techniques biomedical applications such as engineering sensitive cellular monitoring.

Язык: Английский

Dual-Targeting of PDPN-Expressing Synovial Fibroblasts and Macrophages via CLEC-2-Engineered Exosomes for Osteoarthritis Therapy

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Synovitis is often associated with osteoarthritis (OA) and may even precede the onset of OA symptoms. Although targeting synovial inflammation has shown therapeutic promise in OA, synovium's heterogeneous composition, multiple cell types contributing to inflammatory response, indicates that focusing on a single population not provide most favorable results. This investigation employed scRNA-seq tissues from both human murine sources, revealing fibroblasts macrophages expressing high levels Podoplanin (PDPN). These cells constitute approximately 70% total display pro-inflammatory properties. Drawing inspiration unique interaction between PDPN CLEC-2, we engineered mesenchymal stromal cell-derived exosomes overexpress CLEC-2 (Exosome^CLEC-2) encapsulated liquiritigenin-loaded poly (lactic-co-glycolic acid) (PLGA) within Exosome^CLEC-2 membrane (EM^CLEC-2), creating PDPN-targeting nanoparticle system called EM^CLEC-2-PLGA-liquiritigenin (EMPL). Remarkably, EMPL concurrently targets PDPN^high macrophages, exhibiting anti-inflammatory effects both vitro in vivo, preventing cartilage degeneration traumatic model. In summary, our research highlights potential developing platform can target mitigate processes offering novel promising strategy for treatment osteoarthritis.

Язык: Английский