New method sneaks drugs into cancer cells before triggering release

Biomedical engineering researchers have developed an anti-cancer drug delivery method that essentially smuggles the drug into a cancer cell before triggering its release. The method can be likened to keeping a cancer-killing bomb and its detonator separate until they are inside a cancer cell, where they then combine to destroy the cell.

"This is an efficient, fast-acting way of delivering drugs to cancer cells and triggering cell death," says Dr. Ran Mo, lead author of a paper on the work and a postdoctoral researcher in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill. "We also used lipid-based nanocapsules that are already in use for clinical applications, making it closer to use in the real world."

The technique uses nanoscale lipid-based capsules, or liposomes, to deliver both the drug and the release mechanism into cancer cells. One set of liposomes contains adenosine-5’-triphosphate (ATP), the so-called "energy molecule." A second set of liposomes contains an anti-cancer drug called doxorubicin (Dox) that is embedded in a complex of DNA molecules. When the DNA molecules come into contact with high levels of ATP, they unfold and release the Dox. The surface of the liposomes is integrated with positively charged lipids or peptides, which act as corkscrews to introduce the liposomes into cancer cells.

As the liposomes are absorbed into a cancer cell, they are sealed off from the rest of the cell in an endosome - a compartment that walls off all foreign material that gets into a cell.

The environment inside an endosome is acidic, which causes the Dox liposomes and ATP liposomes to fuse together, as well as to the wall of the endosome itself.

Meanwhile, two other things are happening simultaneously. First, the ATP liposomes spill their ATP into the Dox liposomes, releasing the Dox from its DNA cage. Second, the walls of the Dox liposomes create an opening in the endosome, spilling their Dox-rich contents into the surrounding cell - leading to cell death.

In a mouse model, the researchers found that the new technique significantly decreased the size of breast cancer tumors compared to treatment that used Dox without the nanoscale liposomes.

"This work is somewhat similar to previous research we've done with polymer-based nanogels - but there is a key difference," says Dr. Zhen Gu, senior author of the paper and an assistant professor in the joint biomedical engineering program. "The difference is that this liposome-based technique allows us to introduce additional ATP into the cancer cell, releasing the drug more quickly.

"Being able to adjust ATP levels is important because some cancer cells are ATP deficient," Gu adds. "But this technique would work even in those environments."

The paper, "Enhanced Anticancer Efficacy by ATP-Mediated Liposomal Drug Delivery," is published online in Angewandte Chemie. The paper was co-authored by Tianyue Jiang, a Ph.D. student in the joint biomedical engineering program. The research was supported by the National Institutes of Health under grant 1UL1TR001111 and funding from NC State and UNC-Chapel Hill.

Most Popular Now

Pfizer to provide U.S. government with 10 million …

Pfizer Inc. (NYSE: PFE) today announced an agreement with the U.S. government to supply 10 million treatment courses of its investigational COVID-19 oral antiviral candid...

GSK and Vir Biotechnology announce United States g…

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) announced US government contracts totalling approximately $1 billion[1] (USD) to purchase so...

Primary endpoint met in COMET-TAIL Phase III trial…

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Vir) (Nasdaq: VIR) announced headline data from the randomised, multi-centre, open-label COMET-TAIL Phase...

Two billion doses of AstraZeneca’s COVID-19 vaccin…

AstraZeneca and its partners have released for supply two billion doses of their COVID-19 vaccine to more than 170 countries across every continent on the planet in the l...

Merck and Ridgeback's molnupiravir, an oral COVID-…

Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics announced that the United Kingdom Medicines and Healthcare products Re...

Johnson & Johnson COVID-19 vaccine named one o…

The editors of Time announced that the Johnson & Johnson COVID-19 vaccine has been selected as one of Time's Best Inventions of 2021. The vaccine, for which Johnson & ...

New target for COVID-19 vaccines identified

Next generation vaccines for COVID-19 should aim to induce an immune response against 'replication proteins', essential for the very earliest stages of the viral cycle, c...

Repurposing a familiar drug for COVID-19

For the past year and a half, the COVID-19 pandemic has continued to engulf the globe, fueled in part by novel variants and the uneven distribution of vaccines. Every day...

Safety concerns raised for neuroblastoma candidate…

St. Jude Children's Research Hospital scientists looking for drugs to improve survival of children with high-risk neuroblastoma found a promising candidate in CX-5461. Th...

Pfizer and BioNTech receive expanded U.S. FDA emer…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced that the U.S. Food and Drug Administration (FDA) has expanded the emergency use authorization (EUA) of a ...

'Dancing molecules' successfully repair severe spi…

Northwestern University researchers have developed a new injectable therapy that harnesses “dancing molecules” to reverse paralysis and repair tissue after severe spinal ...

A target for potential cancer drugs may, in fact, …

In recent years, much scientific effort and funding has focused on developing drugs that target an enzyme with the unwieldy name of Src homology 2-containing protein tyro...