Acid-Sensitive Nanoparticles Could Be Used for Pancreatic Cancer Treatments

Chinese researchers are looking into acid-sensitive nanoparticles' potential as a potential treatment for pancreatic cancer - drawing inspiration from host defense peptides (HDP).

The research team was led by Professor Yang Lihua from the Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science of the University of Science and Technology of China (USTC) - a part of the Chinese Academy of Sciences. They published their report, titled "pH-Sensitive Nanoparticles Composed Solely of Membrane-Disruptive Macromolecules for Treating Pancreatic Cancer," on the latest ACS Applied Materials & Interfaces.

Drawing from HDPs

Researchers propose using "long-circulating, PH-sensitive nanoparticles" that are exclusively made up of cellular membrane-disrupting molecules to combat tumors from pancreatic cancer. This is made possible with the use of a micelle that imitates HDP as its model.

Host defense peptides are short, cationic, and amphipathic peptides that are parts of eukaryotic organisms' innate immunity. HDPs are responsible for supporting immune response by disrupting the cellular membrane integrity of the pathogens. The researchers use these peptides as the basis for the new membrane disruptive macromolecules, designed to be cationic and amphipathic - having both hydrophilic and hydrophobic parts. These traits allow the macromolecule to exhibit the same membrane disrupting capabilities that could eliminate drug-resistant cancer cells. The onset of drug resistance in cancer cells is efficiently delayed with repetitive medication, suggesting the possibility of addressing the problem of cancer cells resisting conventional medication.

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However, the membrane disruptive macromolecules have no way of distinguishing normal cells from cancer cells, presenting another challenge for the researchers. They then used an acid-sensitive, membrane disruptive micelle (M-14K) as its nanoparticles model.

The study's long-circulating nanoparticle exhibited acid-activated cytotoxicity for cancer cells and fibroblast cells realized through an acid-activatable disruption of cellular membrane integrity. Researchers verified the penetrating capability of their nanoparticles on the stromal barrier, eliminating the cancer cells within. They conducted in vitro observations with 3D cell spheroids and in vivo with mouse models having BxPC-3 tumors.

In the animal experiments, they found out that the nanoparticle suppressed the expression of extracellular matrix components, reducing the tumor tissue into a less dense structure, remodeling the stroma, all without encouraging tumor metastasis.'

Pancreatic Cancer in the US

One of the challenges in treating pancreatic cancer tumors is the dense stroma that acts as a barrier shielding the cancer cells. This layer of connective tissues severely inhibits the effectiveness of medications. Usually, adjuvants are used prior to administering the chemotherapy drug gemcitabine to increase its infiltration capabilities.

A 2020 estimate from the Cancer.Net website estimates that about 57,600 adults in the United States face an increased risk of pancreatic cancer, making up 3 percent of all cancers in the country. Pancreatic cancer is often divided into two types, based on whether it began in the pancreas' exocrine or endocrine component. The most common type of this cancer is the growth of an exocrine tumor called exocrine adenocarcinoma, which constitutes up to 93 percent of all recorded pancreatic cancer cases.