Cationizable lipid micelles as vehicles for intraarterial glioma treatment

Abstract

The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.

Strategies for Improved Intra-arterial Treatments Targeting Brain Tumors: a Systematic Review

“…When combined with BBB disruption induced by focused ultrasound, intra-arterial liposome injection increases their deposition into tumor tissue of C6 tumor-bearing rats ( 158 ). Similarly, application of cationizable lipid micelles ( 163 ) with cationic short peptides such as the cell-penetrating trans-activator of transcription (TAT) was shown to increase the uptake of micelles ( 165 ) and can be used for selective drug delivery to gliomas. The translocation efficiency of nanoparticles is not only determined by surface charge.…”

“…The treatment effect was reported to last for more than 4 h (175). Furthermore, TCH is sufficient to enhance early regional deposition of nanoparticles such as micelles (163)(164)(165) and liposomes (158)(159)(160)(161)(162) into tumor tissues. This provides a novel approach for targeted intra-arterial tumor therapy ( Table 3).…”

Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

“…The attraction of nanotechnology for intra-arterial drug delivery is multifold. Various authors noted these small particles could not only be loaded with different therapies, including small-molecule inhibitors, gene therapies or siRNAs, but could also be modified to cross the BBB through a variety of transport mechanisms and remain at the target site for longer periods of time to allow for a gradual release of loaded therapeutics [23,[105][106][107][108][109][110][111][112][113].…”

“…Drug modification or loading into nanoparticles can allow for improved BBB penetration, tumor targeting, and drug-tumor contact time of active compounds [114][115][116]. Labeled therapeutic agents as well as theragnostic nanoparticles have the potential to be used with advanced imaging techniques [50,106,109]. From a procedural point of view, optimizing currently available endovascular technologies and combining them with innovative strategies, such as superselective intra-arterial cerebral infusion or transient cerebral hypoperfusion/flow arrest, is crucial to ensure procedural safety and effect [31,61,89].…”

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

“…Plain and CCR2-targeting micelles were prepared as follows: mPEG-DSPE/NHS-PEG-DSPE/DiD (98/2/0.5) were dissolved in chloroform and mixed with the CCR2 antagonist dissolved in methanol. 14,18,19 The small molecule antagonist CCR2 was loaded into the lipid micelles at 1:22 molar ratio, which corresponds to a loading of 4.5% w/w. The solvent was removed by rotary evaporation to yield a lipid film.…”