Study sheds light on mechanism of liposome accumulation in tumors


IMAGE: Dmitri Simberg, PhD
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Credit: CU Cancer Center

The brand-new study, entitled “Liposomal Extravasation and Accumulation in Tumors as Studied by Fluorescence Microscopy and Imaging Depend on the Fluorescent Label,” was released on July 1, 2021, in the prominent journal of the American Chemical Society, ACS Nano.

Liposomes, a type of nanoparticle, are small, fat-soluble blisters (little, fluid-filled sacs) made from lipids, or fats. They are primarily utilized to provide cancer-fighting drugs to tumors, given that liposomes are not water soluble and can safeguard some drugs versus breaking down in the body.

Comparing fluorescent labels on liposomes for improved growth imaging

In the brand-new study, Simberg and his partner Irina Balyasnikova, PhD, from the Department of Neurological Surgery at Northwestern University, wished to identify whether the accumulation of liposomes in tumors depends on the type of fluorescent label utilized.

“It’s very important for the liposome to get out to the tumor blood vessels in order to reach tumor cells and other cells in the microenvironment. So, we asked whether liposome accumulation in tumors depends on which fluorescent label you use,” Simberg describes.

“It’s the first finding of its kind, showing that different lipids have different abilities to accumulate in tumors.” – Dmitri Simberg, PhD

To achieve this, they made liposomes consisting of 2 various classes of fluorescent lipids in the exact same liposome: indocarbocyanine lipids (ICLs) and fluorescent phospholipids (FPLs). Then they injected them into breast cancer and brain cancer mouse designs and utilized fluorescent microscopy and imaging to compare just how much of each label collected in the tumors.

Both types of fluorescent labels at first collected in the growth capillary. However, with time, the ICLs continued to collect, topping a substantially bigger growth location and reaching immune and growth cells, while the FPLs rapidly deteriorated and vanished from the tumors.

“What we found is that even when injected into the same liposome, ICLs showed remarkable accumulation and extravasation (infiltrating the tumors), while FPLs, though a very similar type of fluorescent group, did not show much extravasation and essentially disappeared,” Simberg states.

“It’s the first finding of its kind, showing that different lipids have different abilities to accumulate in tumors,” he includes.

Results might result in enhanced liposomal drug shipment

The group’s findings unlock to enhanced cancer drug-delivery systems.

“There is a lot of interest in using lipids as a kind of shuttle to get the drugs into tumors,” Simberg states. “It’s an exciting opportunity to enhance drug delivery in different tumors, particularly glioma, a type of brain tumor that’s especially difficult to penetrate.”

Although a lot of laboratories make liposomes and nanoparticles, there has actually not been much mechanistic understanding of precisely how they connect with tumors and how they cross the endothelial barrier. “We’re really advocating for studies that offer a deeper mechanistic understanding of how these drug-delivery systems work,” Simberg states.

Simberg states the most impactful part of this paper and his laboratory’s continuous research study is its focus on comprehending the mechanics and structure of lipids that identify the performance of growth accumulation.

The next action in the group’s research study will be research studies to attempt extra fluorescent lipids. “In this paper, we compared two lipid types, but we want to expand on that to build a large library of fluorescent lipids and use the most efficient ones to deliver anticancer drugs, eventually testing them for therapeutic efficacy in glioma and other tumor models,” Simberg states.

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