Development of polyethylene glycol-modified gold nanoparticles for the delivery of Lutetium-177- radiopharmaceuticals based on antibodies

• Published in: Journal of drug delivery science and technology 2024-10, Vol.100, p.106104, Article 106104
• Main Authors: Maskur, Wongso, Hendris, Humani, Titis Sekar, Effendi, Nurmaya, Palangka, Citra R.A.P., Pujiyanto, Anung, Setiawan, Herlan, Juliyanto, Sumandi, Ridwan, Muhammad, Ritawidya, Rien
• Format: Article
• Language: English
• Subjects: Drug delivery vehicles; Gold nanoparticles; Lutetium-177; Polyethylene glycol; Radiopharmaceuticals; Targeted therapy
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2024.106104

Lutetium-177-labeled radiopharmaceuticals have been used clinically for the treatment of various malignancies in nuclear medicine. The main characteristics of lutetium-177 (177Lu), such as its concurrent emission of imageable gamma photons (208 keV (11 %) and 113 keV (6.4 %)) as well as therapeutic β− emission [β(max) = 497 keV] make it one of the radionuclides of choice to treat various types of cancers. In general, for therapeutic purposes, the synthesis of [177Lu]Lu-labeled radiopharmaceuticals requires high specific activity of 177Lu which can be produced by a nuclear reactor with high neutron flux. Unfortunately, only a few countries have benefited from this type of reactor. The use of low specific activity of 177Lu will lead to a low loading of this radionuclide in cancer cells, and thus decrease its efficacy. Accordingly, recent efforts have been made to explore suitable drug delivery vehicles to improve the 177Lu loading in targeted cancers. Due to their remarkable size and suitable surface properties, gold nanoparticles (AuNPs) have attracted attention among scientists as suitable vehicles to carry a high amount of drugs to targeted diseases. Hence, the presence of AuNP in a [177Lu]Lu-labeled radiopharmaceutical complex increases the amount of 177Lu. Overall, delivering sufficient radioactivity of 177Lu to cancer cells is very critical, which can be realized by conjugating the [177Lu]Lu-complex with AuNPs. This review summarizes recent advances in the development of AuNPs and discusses their potential as a drug vehicle in delivering substantial therapeutic radionuclide 177Lu into cancerous tissues. [Display omitted] •AuNP can assist with the absorption of higher radiation doses of radioactive 177Lu.•Antibodies can be conjugated to AuNP using either covalent or non-covalent methods.•Polyethylene glycol (PEG) linkers play an important role in radiolabeling of AuNP.