
International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 14059 - 14074
Опубликована: Дек. 1, 2024
Background:The dense and fibrotic nature of the pancreatic tumor microenvironment significantly contributes to invasion metastasis.This challenging environment acts as a formidable barrier, hindering effective drug penetration delivery, which ultimately limits efficacy conventional cancer treatments.Gold nanoparticles (AuNPs) have emerged promising nanocarriers overcome extracellular matrix barrier; however, their limited targeting precision, poor delivery efficiency, insufficient photothermal conversion present challenges.Methods: We developed triphenyl phosphonium-functionalized high-branch gold nanoparticles, denoted Dox@TPAu, enhance capabilities.The targeted penetration, biopharmaceutical pharmacokinetic properties Dox@TPAu were characterized, synergistic therapeutic effect was evaluated by BxPC-3 xenograft mouse model.Results: exhibits superior efficiency (91.0%) alongside high loading (26%) photo-triggered drug-release potential.This system adeptly accumulates at sites due its unique properties, enabling localization within cells mitochondria stromal fibroblasts.This disrupts mitochondrial function transfer-processes crucial for energy production, metabolism, cell signaling microenvironment.Pharmacokinetic analyses revealed an optimal spatiotemporal distribution site.This strategic accumulation enables precise disruption both physical barrier cells, enhancing treatment through near-infrared light-triggered local chemo-photothermal therapy.Conclusion: Our findings demonstrate that this innovative strategy effectively leverages mitochondriatargeting, virus-like AuNPs efficient depletion, presenting approach treatment.
Язык: Английский