LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques

Due to the high risk of tearing and rupture,vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases.Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event,but the efficiency is still low and undesirable.Herein,we rationally design and engineer the low-intensity focused ultrasound(LIFU)-responsive FPD@CD nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane(PFH)into biocompatible PLGA-PEG-PLGA nanoparticles(PPP NPs)and then attaching dextran sulphate(DS)onto the surface of PPP NPs for targeting delivery.DS,as a typical macrophages-targeted molecule,can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization(ADV)effect.In addition,the introduction of DiR and Fe3O4 endows nanomedicine with near-infrared fluorescence(NIRF)and magnetic resonance(MR)imaging capabilities.The engineered FPD@CD nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes.A reduction of 49.4%of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period.This specific,efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.

Persistent luminescence phosphor as in-vivo light source for tumoral cyanobacterial photosynthetic oxygenation and photodynamic therapy

Tumor oxygenation level has been regarded as an attractive target to elevate the efficiency of photodynamic therapy(PDT).Cyanobacterial photosynthesis-mediated reversal of tumor hypoxia could enable an oxygen-boosted PDT,but is limited by scant penetration depth and efficiency of external light.Herein,aiming at the dual purposes of reducing biological toxicity induced by long-term light irradiation and alleviating hypoxia,we here introduce a novel-designed CaAl2O4:Eu,Nd blue persistent luminescence material(PLM)as the in vivo light source after pre-excited in vitro.The ingenious construction of blue-emitting PLM with“optical battery”characteristics activates cyanobacterial cells and verteporfin simultaneously,which performs the successive oxygen supply and singlet oxygen generation without the long-term external excitation,resulting in the modulated tumor hypoxic microenvironment and enhanced photodynamic tumor proliferation inhibition efficiency.Both in vitro cellular assessment and in vivo tumor evaluation results affirm the advantages of self-produced oxygen PDT system and evidence the notable antineoplastic outcome.This work develops an irradiation-free photosynthetic bacteria-based PDT platform for the optimization of both oxygen production capacity and light utilization efficiency in cancer treatment,which is expected to promote the clinical progress of microbial-based photonic therapy.