1. Journal Source: Drug Delivery

2. Title: Ultrasound‑triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma

3. Research Highlights: In this work, an ultrasound-responsive platelet delivery vehicle was designed. A prodrug was combined with an efflux inhibitor to achieve stable loading of fluorescein inside platelets, constructing the FL@plt system. Taking advantage of the innate tumor-homing property of platelets for targeted delivery of the sonosensitizer, drug release from the vehicle is triggered by ultrasound. Sonodynamic therapeutic effects against glioblastoma are exerted through dual pathways including direct DNA damage and suppression of DNA repair.

4. Innovations: 1. The sonosensitizer is loaded via simple incubation using a prodrug combined with an efflux inhibitor, avoiding interference with platelet functions caused by complicated chemical modification; 2. Platelets are adopted as biological carriers to realize targeted delivery of the sonosensitizer to glioblastoma with ultrasound-controllable drug release; 3. A novel mechanism underlying FL-SDT is uncovered, which can downregulate HIF‑1α through two degradation pathways and inhibit the expression of downstream DNA repair proteins.

5. Material Development
(1) Materials: Fluorescein diacetate (FDA), probenecid, mouse platelets, for the preparation of FL@plt ultrasound-responsive platelet vehicles
(2) Functions: Platelets possess tumor-homing capacity; they are activated and release fluorescein upon ultrasound stimulation; probenecid inhibits MRP1-mediated efflux to improve intracellular drug retention; fluorescein acts as a sonosensitizer that generates reactive oxygen species under ultrasound to damage tumor cells.

6. Extended Perspectives: This platelet-based biological delivery platform can be expanded for co-loading multiple therapeutic components. Further research can explore the regulatory effects of the ubiquitin-proteasome pathway and autophagy-lysosome pathway in tumor sonodynamic therapy. This strategy can be translated for application to other brain tumor models restricted by the blood-brain barrier.

#Biomaterials #PlateletVehicles #SonodynamicTherapy #Glioblastoma #TumorTargetedDelivery #Nanomaterials #ScientificResearch #LiteratureSharing

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