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Advances in Radiotherapy
& Nuclear Medicine Radionuclide-carrying liposomes

peritoneum. Therapeutic liposomes are cleared from agents to sentinel lymph nodes after injection into
the peritoneal cavity at a slower rate compared to free interstitial or subcutaneous spaces around the tumor. Sites
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chemotherapy drugs. Zavaleta et al. developed a method of infection, cancer, inflammation, cardiovascular disease,
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of further increasing the retention of therapeutic liposomes cerebral ischemia, and stroke tend to have significantly
with peritoneal administration. The liposomes developed higher levels of macrophages/mononuclear cells that are

by the group were coated in biotin, and avidin was injected part of the MPS. Therefore, the clearance of liposomes by
into subjects after intraperitoneal administration of the the MPS, while sometimes seen as a disadvantage, could
biotin-coated liposomes. This was reported to cause also be used to target certain sites that have abnormally
aggregation of the liposomes with crosslinking of avidin elevated levels of macrophages present. It has been
with biotin-coated liposomes. This led to the retention of shown that an increased number of macrophages within
liposomes in the peritoneal cavity and in the lymph nodes the tumor, tumor-associated macrophages, is associated
that drain the peritoneal cavity. These lymph nodes are with a decreased prognosis. Radiolabeled liposomes
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likely to contain metastatic cancer cells. 26 are ideally suited for targeting tumors associated with
macrophages since liposomes are highly phagocytosed by
8. Liposomes and the immune system macrophages. This ideal fit of nanomedicine for targeting
The human body typically perceives drug capsules as tumor-associated macrophages has been noted by other
foreign material, which catalyzes an immune response. investigators. 33
Consequently, liposomes have shown high rates of One way to limit the uptake of liposomes by the MPS
interaction with cells of the mononuclear phagocyte is to alter their membrane. The liposome membrane can
system (MPS). Due to this, many studies have shown that be masked with chemicals such as polyethylene glycol
liposomes naturally accumulate in parts of the immune (PEG) to imitate the membranes of red blood cells,
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system, such as the liver and spleen. This phenomenon is which reduces recognition by the MPS and increases the
a common challenge with all types of liposomes carrying circulation time of liposomes. 34,35 A longer circulation time
radionuclides, so strategies for avoiding clearance by the and greater levels of accumulation in tumors have been
MPS and accumulation of liposomes in the liver and seen with PEG-liposomes. Unfortunately, the strategy of
spleen should be explored to enhance the therapeutic “PEGylation” does not appear to prevent a high uptake of
performance of radionuclide-carrying liposomes. Kelly liposomes by the liver and spleen compared to other parts
et al. describe how the uptake of liposomes by the MPS can of the body. It is the “PEGylated” liposomes that are used
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be affected by liposome size, charge, and the incorporation in the previously mentioned FDA-approved drug, Doxil .
® 36
of ligands into the liposomal structure. Specifically, smaller Beyond the MPS, liposomes can also be affected
liposomes have shown lower rates of clearance by the MPS by high-density lipoprotein (HDL) and low-density
because there is a decreased risk of opsonization by plasma lipoprotein (LDL) present in the blood. Interaction with
proteins present in the blood. It has also been shown that these lipoproteins can warp liposomal structure and cause
liposomes with a high electrostatic charge are more likely undesirable instability in the bloodstream. However, it
to be cleared by the MPS system. 29
has been shown that the addition of cholesterol to the
Umeda et al. recently described a method to decrease structure of the liposomes offers greater levels of stability.
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the accumulation of liposome-targeted diagnostic It has been shown that the inclusion of cholesterol in
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or radiotherapeutic nuclides in the MPS. In their liposomal structure inhibits liposomes from being turned
research, a therapeutic radionuclide was chelated to into HDL or LDL. Furthermore, molecules can be attached
ethylenedicysteine, which cleared much more rapidly to liposomal membranes when anchored by cholesterol. 37
from normal liver and spleen compared to a conventional
radiochelated molecule. Their method showed good 9. Liposomes that allow for triggered
retention in a targeted tumor. The rapid clearance from the release
MPS allowed for improved diagnostic imaging, and based Liposomes can be modified to offer higher levels of control
on distribution studies should greatly decrease radiation with timed release of internal contents. Ta and Porter
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exposure to the MPS of the liver and spleen while still constructed thermosensitive liposomes that can remain
delivering a high dose to the tumor. stable until triggered by externally controlled heat to
The high accumulation of standard liposome release their internal contents. Higher temperatures have
formulations within the MPS can also be a potential also been shown to dilate gaps in tumor vasculature, so
advantage. La-Beck et al. suggest how the uptake of selective heating of cancerous regions can further increase
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liposomes by the MPS could be used to deliver imaging the tendency of liposomes to leak out of blood vessels into

Volume 2 Issue 4 (2024) 6 doi: 10.36922/arnm.4373