Selective ultrasound contrast enhancement in the tumor by nanocapsules with perfluorooctylbromide: effect of PLGA–PEG proportion

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis‐driven stimuli‐responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood‐brain barrier (BBB) trafficking and lack of GBM targeting—two major hurdles for anti‐GBM therapies. NPs are dual‐surface tailored with a i) brain‐targeted acid‐responsive Angiopep‐2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L‐Histidine moiety that provides NP preferential accumulation into GBM cells post‐BBB crossing. In tumor invasive margin patient cells, the stimuli‐responsive multifunctional NPs target GBM cells, enhance cell uptake by 12‐fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long‐term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli‐responsive multifunctional NPs as an effective anti‐GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.

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Stimuli‐Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood‐to‐Brain Trafficking and Tumor Targeting

Martins

Araújo

Malfanti

et al. 2023

Small

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Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury

Zhang

Zhu

Huang

et al. 2023

Green Processing and Synthesis

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Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic-co-glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells (P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats (P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone (P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.

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Selective ultrasound contrast enhancement in the tumor by nanocapsules with perfluorooctylbromide: effect of PLGA–PEG proportion

Abstract: Effects of different PLGA–PEG proportion on nanoparticles' morphology, elastic modulus, mononuclear cell uptake rate and ultrasound contrast enhancement.

Cited by 2 publications

References 28 publications

Stimuli‐Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood‐to‐Brain Trafficking and Tumor Targeting

Stimuli‐Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood‐to‐Brain Trafficking and Tumor Targeting

Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury

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