Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment

Abstract

The tumour microenvironment regulates tumour progression and the spread of cancer in the body. Targeting the stromal cells that surround cancer cells could, therefore, improve the effectiveness of existing cancer treatments. Here, we show that magnetic nanoparticle clusters encapsulated inside a liposome can, under the influence of an external magnet, target both the tumour and its microenvironment. We use the outstanding T2 contrast properties (r2=573-1,286 s(-1) mM(-1)) of these ferri-liposomes, which are ∼95 nm in diameter, to non-invasively monitor drug delivery in vivo. We also visualize the targeting of the tumour microenvironment by the drug-loaded ferri-liposomes and the uptake of a model probe by cells. Furthermore, we used the ferri-liposomes to deliver a cathepsin protease inhibitor to a mammary tumour and its microenvironment in a mouse, which substantially reduced the size of the tumour compared with systemic delivery of the same drug.

Cathepsin C is a tissue-specific regulator of squamous carcinogenesis

“…Unfortunately, current CtsC inhibitors exhibit poor pharmacokinetics (Guay et al 2010), and even the broad-spectrum cysteine Cts inhibitor JPMOEt exhibits poor bioavailability in mammary carcinomas and lungs when administered systemically (Schurigt et al 2008). Targeted delivery of CtsC inhibitors to the tumor microenvironment, such as through encapsulation in ferri-liposomes (Mikhaylov et al 2011), may be the best approach for moving CtsC inhibitors into the clinic, where they may act to inhibit stromal-driven angiogenesis in SCC.…”

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

“…In this respect, to the best of our knowledge, the only ferrimagnetic secondary structure that has been studied so far for its outstanding visualizing (T 2 -weighted contrast properties) as well as drug-delivering actions, is a newly designed liposome-encapsulated magnetic nanoparticle cluster. 58 This system shows an unprecedented r 2 of 1286 mM -1 s -1 but at a higher magnetic field of 2.35 T, thus leaving the CNCs a valid alternative.…”

Antitumor activity of low-dimensional alumina structures

“…Some research has been devoted to developing and investigating the hybrid systems made of nanomaterials and biological cells and also using nanomaterials for the targeted cell therapy [1,2].…”