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Easy and rapid binding of a targeting molecule and a Radiotracer to a drug nanocarrier for cancer treatment


credit: Biomolecules (2023). DOI: 10.1021/acs.biomac.2c01539

The ideal cancer-fighting nanovesicle would have three functions: 1) a precise targeting molecule to preferentially bind to surface markers on cancer cells, 2) a highly binding radionuclide signal that would allow a PET scan to locate vesicles in the body, and 3) the ability to carry and release drug therapy , like chemotherapy, in a cancer tumor.

It also fulfills two other requirements – having a simple and easy manufacturing method, and being biocompatible and biodegradable in the body.

A team from the University of Alabama at Birmingham has now described a small polymer that – in preliminary preclinical trials – appears to counter these hurdles. Each polymericum is a thin-walled hollow sphere, but it’s the coating on the polymer that’s a step further.

The 60nm triblock polymer copolymers contain hydrolyzable tannic acid, or TA, adsorbed on the surface through hydrogen bonding. This TA, in turn, is able to quickly and stably bind a monoclonal antibody-targeting molecule to a zirconium radionuclide, or Zr, without the need to build specific linkers, such as chelates, say Eugenia Kharlampiev, PhD, and Susan E. Lapi, Ph.D., UAB team leaders. Their study has been published in the journal Biomolecules.

In this study, we developed a simple approach for a chelator-free modification of PVPON.5-PDMS30-PVPON5 Tri-block copolymer nanoparticles, about 60 to 80 nanometers in diameter, with a layer of polyphenols can be used at the same time to solidify 89Kharlampiev, Distinguished Professor in the Faculty of Arts and Sciences at UAB, said: “Chemistry5 It is a short block polymer composed of five monomers and PDMS30 is a longer, 30-monomer, hydrophobic block copolymer within a ternary-block copolymer.

Breast cancer is one of the most common cancers, and global death rates remain high. Systemic drugs or therapeutic antibodies are current treatments, but they are often associated with heart damage and dysfunction. Image-guided drug delivery to the solid tumor could allow efficient pharmacological activity with low drug toxicity.

said Labbe, MD, director of the UAB Cyclotron facility and professor in the Department of Radiology. “The radioactive labeling method developed here can provide stable binding to a wide range of isotopes without radioactive optical filtration from the vesicle membrane in vivo. Notably, this approach integrates the advantages inherent in membrane polyphenol polymers with the benefit of rapid stabilization of breast cancer cells- Link targeting.

In the study, TA on the polymer bound 89Zr4+ Radionuclides through nonspecific ion coupling, and TA also bind the trastuzumab monoclonal antibody, or Tmab, through hydrogen bonding and ion coupling. There was excellent retention of 89Zr for up to seven days, as confirmed by positron emission tomography scans in healthy mice.

“Non-covalent anchoring of Tmab to membrane polymers can be very useful for nanoparticle modification compared to currently developed covalent methods, as it enables easy and rapid integration of a wide range of target proteins,” said Kharlampiev. “Given the ability of these polymers to encapsulate and release anticancer therapeutics, they can be further expanded as precision-targeted therapeutic carriers to advance human health through highly effective drug delivery strategies.”

One hour incubate the TA polymers in solution 89Zr-oxalate resulted in a yield of radiolabeling by 97 per cent, and this yield remained constant over the course of one, three and seven days. The labeled polymers were not cytotoxic when incubated in vitro with two cancer cell lines for up to four days. Moreover, binding 89Zr to polymersomes with Tmab already attached also had high yields of 97 percent and stability within seven days. UAB researchers say these binding outputs are high enough for clinical use.

After that, the stable retention of the 89Zr on TA polymers has been demonstrated indirectly in mice.

Free biodistribution 89It was previously reported that the radioactive tracer Zr is highly localized in the vertebral column and femur of animals due to zirconium chelation with phosphate moieties in the bone. UAB researchers found that, when it’s free 89Zr was injected into mice, and most of it was located in the femur after 24 h, as measured by positron emission tomography. A completely different biodistribution is seen when 89Zr-TA polymers were injected into mice. Little radioactivity was found in the bones. Instead, almost all of the radioactivity was in the spleen and liver. This site represents the known expected filtering of nanoparticles by a mononuclear phagocytosis system for nanomaterials larger than 6–8 nm.

The significant difference observed between free biodistribution 89Zr and the metal-labelled radioactive vesicle are important, Labbe said, because they demonstrate an unimpeded ability of the polymeric nanocarrier to be tracked in vivo.”

The strong imaging contrast was retained in the mice over seven days, which is further evidence of the tight retention of 89Zr on TA-polymers.

capacity 89Zr-Tmab-TA-polymersomes have been shown to target HER2-positive cancer cells in vitro by differential binding of nanovesicles to HER2-positive versus HER2-negative breast cancer cells. The researchers say more tests are needed to target breast cancer tumors in animals.

Co-authors of the study, “Direct Radiolabeling of Trastuzumab-Targeted Trebox Copolymer Vesicles Using 89Zr for positron emission tomography,” Veronika Kozlovskaya, Department of Chemistry, Abha University, and Maxwell Ducharme, Department of Radiology, Abha University.

Other co-authors with Kharlampieva, Lapi, Kozlovskaya, and Durcharme are Maksim Dolmat and James M. Omweri, UAB Chemistry Department; and Volkan Tekin, Department of Radiology at Abu Dhabi University.

more information:
Veronika Kozlovskaya et al, Direct Radiolabeling of Trastuzumab Targeting Treblock Copolymer Vesicles with 89Zr for Positron Emission Tomography, Biomolecules (2023). DOI: 10.1021/acs.biomac.2c01539

Provided by the University of Alabama at Birmingham

the quote: Easy and Quick Binding of Targeting Molecule and Radiotracer to Nanocarrier for Drugs for Cancer Treatment (2023, April 10) Retrieved April 10, 2023 from https://phys.org/news/2023-04-easy-quick-molecule-radiotracer-drug. programming language

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