4.8 Article

Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 332, Issue -, Pages 301-311

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2021.03.006

Keywords

Liposomes; Glucose modification; Drug delivery; Tumor-bearing mice; Cancer; Radiolabeling

Funding

  1. Ministry of Education, Science and Technological Development of Republic of Serbia [451-03-68/2020-14/200146]

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The use of glucose-modified liposomes (GML) enhances the delivery of drugs to tumor cells through glucose transporters, resulting in significantly better accumulation in tumor tissues compared to non-glucose liposomes (NGL). This study demonstrates the potential for GML in targeted cancer therapy using radiotracking for biodistribution studies.
Liposomes are promising drug?s delivery systems due to decreased toxicity of the liposome-encapsulated drug, but wider clinical application requires their more efficient tumor targeting with uptake, controlled drug release and higher shelf life. The unique metabolic characteristics of cancer cells based on higher demand for energy and therefore increased glucose utilization were exploited in the design of glucose modified liposomes (GML) with the aim to provide increased tumor targeting via glucose transporters and increased ability of drug delivery into tumor cells. Tumor accumulating potential of GML and non-glucose liposomes (NGL) were investigated on CT26 and LS174T tumor-bearing mice by simple and reliable radiotracer method using 177Lu as radioactive marker. Both liposomes, GML and NGL were radiolabeled in high radiolabeling yield, showing high in vitro stability in biological media, as the main prerequisite for the biodistribution studies. Tumors displayed significantly better accumulation of 177Lu-GML with the maximum uptake 6 h post-injection (5.8 ? 0.2%/g in LS174T tumor and 5.1 ? 0.5%/g in CT26 tumor), compared to negligible uptake of 177Lu-NGL (0.6 ? 0.1%/g in LS174T tumor and 0.9 ? 0.2%/g in CT26 tumor). Results of comparative biodistribution studies of 177Lu-NGL and 177Lu-GML indicate that increased accumulation of GML is enabled by glucose transporters and subsequent endocytosis, resulting in their prolonged retention in tumor tissues (up to 72 h). Direct radiolabeling of liposomes with 177Lu may be used not only for biodistribution studies using radiotracking, but also for cancer treatment.

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