Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nanodrug targeting breast cancer cells from the inside adds weapon: Immune system attack

12.08.2013
The multipronged approach directly attacks cancer cells, blocking the growth of cancer-supporting blood vessels and stimulating an antitumor immune response

A unique nanoscale drug that can carry a variety of weapons and sneak into cancer cells to break them down from the inside has a new component: a protein that stimulates the immune system to attack HER2-positive breast cancer cells.

The research team developing the drug – led by scientists at the Nanomedicine Research Center, part of the Maxine Dunitz Neurosurgical Institute in the Department of Neurosurgery at Cedars-Sinai Medical Center – conducted the study in laboratory mice with implanted human breast cancer cells. Mice receiving the drug lived significantly longer than untreated counterparts and those receiving only certain components of the drug, according to a recent article in the Journal of Controlled Release.

Researchers from the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, the Division of Surgical Oncology at UCLA, and the Molecular Biology Institute at UCLA also participated in the study.

Unlike other drugs that target cancer cells from the outside, often injuring normal cells as a side effect, this therapy consists of multiple drugs chemically bonded to a "nanoplatform" that functions as a transport vehicle.

HER2-positive cancers – making up 25 to 30 percent of breast and ovarian cancers – tend to be more aggressive and less responsive to treatment than others because the overactive HER2 gene makes excessive amounts of a protein that promotes cancer growth. One commonly used drug, Herceptin (trastuzumab), often is effective for a while, but many tumors become resistant within the first year of treatment and the drug can injure normal organs it contacts.

But Herceptin is an antibody to the HER2 gene – it naturally seeks out this protein – so the research team used key parts of Herceptin to guide the nanodrug into HER2-positive cancer cells.

"We genetically prepared a new 'fusion gene' that consists of an immune-stimulating protein, interleukin-2, and a gene of Herceptin," said Julia Y. Ljubimova, MD, PhD, professor of neurosurgery and biomedical sciences and director of the Nanomedicine Research Center. "IL-2 activates a variety of immune cells but is not stable in blood plasma and does not home specifically to tumor cells. By attaching the new fusion antibody to the nanoplatform, we were able to deliver Herceptin directly to HER2-positive cancer cells, at the same time transporting IL-2 to the tumor site to stimulate the immune system. Attaching IL-2 to the platform helped stabilize the protein and allowed us to double the dosage that could be delivered to the tumor."

Ljubimova led the study with Manuel Penichet, MD, PhD, associate professor of surgery, microbiology, immunology and molecular genetics at the University of California, Los Angeles, David Geffen School of Medicine. Ljubimova said the UCLA collaborators developed the fusion gene, and Cedars-Sinai chemists Eggehard Holler, PhD, professor in the Department of Neurosurgery, and Hui Ding, PhD, assistant professor, performed the technically difficult task of attaching it to the nanoplatform. Ding is the journal article's first author.

The researchers also attached other components, such as molecules to block a protein (laminin-411) that cancer cells need to make new blood vessels for growth.

The nanodrug, Polycefin, is in an emerging class called nanobiopolymeric conjugates, nanoconjugates or nanobioconjugates. They are the latest evolution of molecular drugs designed to slow or stop cancers by blocking them in multiple ways. Polycefin is intended to slow their growth by entering cells and altering defined targets. The new version also stimulates the immune system to further weaken cancers.

"We believe this is the first time a drug has been designed for nano-immunology anti-cancer treatment," Ljubimova said.

Bioconjugates are drugs that contain chemical "modules" attached (conjugated) to a delivery vehicle by strong chemical bonds. The nanoconjugate exists as a single chemical unit, and the tight bonds prevent the components from getting damaged or separated in tissues or blood plasma during transit. With inventive drug engineering, the anti-tumor components activate inside tumor cells.

"More study is needed to confirm our findings, improve the effectiveness of this approach and shed light on the anti-cancer mechanisms at work, but it appears that the nanobioconjugate may represent a new generation of cancer therapeutics in which we launch a multipronged attack that directly kills cancer cells, blocks the growth of cancer-supporting blood vessels and stimulates a powerful antitumor immune response," Ljubimova said, adding that this and previous animal studies have found the nanodrug to be a safe and efficient delivery platform.

Nano researchers manipulate substances and materials at the atomic level, generally working with substances smaller than 100 nanometers. Cedars-Sinai's nanoconjugate is estimated to be about 27 nanometers wide. A human hair is 80,000 to 100,000 nanometers wide.

This study was supported in part by grants from the National Institutes of Health/National Cancer Institute (R01CA123459, U01CA151815, R01CA136841, K01CA138559. Additional support came from the UC MEXUS-CONACYT Fellowship Program, the Howard Hughes Medical Institute Gilliam Fellowship, the Whitcome Fellowship of the Molecular Biology Institute at UCLA, ANPCyT-FONARSEC PICT-PRH 2008-00315, the CONICET PIP no. 114-2011-01-00139, and the UBACYT No 200-2011-02-00027. The UCLA Flow Cytometry Core Facility is supported by NIH awards CA16042 and AI28697, the Jonsson Cancer Center, the UCLA AIDS Institute and the UCLA School of Medicine.

Citation: Journal of Controlled Release, "Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer"

Sandy Van | Cedars-Sinai News
Further information:
http://www.cedars-sinai.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>