New promising treatment uses smart nanoparticles to target lung cancer


Date:
July 15, 2020
Source:
Lund University
Summary:
A new and promising approach for treatment of lung cancer has been
developed. The treatment combines a novel surgical approach with
smart nanoparticles to specifically target lung tumors.



FULL STORY ==========================================================================
A new and promising approach for treatment of lung cancer has been
developed by researchers at Lund University. The treatment combines a
novel surgical approach with smart nanoparticles to specifically target
lung tumors. The new study has been published in the July issue of
Advanced Therapeutics.


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Lung tumors are often difficult to remove using current surgical
techniques due to their location in the lung or the fact that there are multiple tumors which are too small to observe. Tumors also develop
natural barriers to prevent drugs and immune cells from reaching the
tumor cells.

"Therefore, patients often receive high doses of chemotherapeutics which
are circulated through the entire body and lead to major side effects
in other organs. While a number of new experimental therapies have been developed for lung cancer and have shown promise in the lab, a major
remaining challenge has been how to deliver the right drug specifically
to these difficult to reach tumors," explains Darcy Wagner, Associate
Professor and Head of the research group.

In order to overcome this challenge, the researchers behind the new
study: Deniz Bo"lu"kbas and Darcy Wagner, researchers of the Lung Bioengineering and regeneration group, and colleagues developed a
novel surgical technique which introduces the nanoparticles only into
the blood vessels of the lung. The blood vessels around and in tumors
are different than those in normal organs. The researchers used this
difference to their benefit to direct nanoparticles to the interior of
large and dense solid lung tumors.

Bo"lu"kbas and colleagues also used animal models which have a full immune system and closely resemble the types of lung tumors that patients have.

"Using this technique, which we call 'organ restricted vascular delivery' (ORVD), we were able to see lung cancer cells with the delivered
nanoparticles inside of them -- something which has not been achieved previously in these types of lung cancer animal models, which closely
resemble the clinical scenario," explains Deniz Bo"lu"kbas, post-doctoral fellow and leading author of the article.

As an extra level of specificity, the nanoparticles were engineered to
only release their drug content upon a specific cue which is present in
the tumor area. This reduces the risk that the drugs contained within
the nanoparticle will cause damage in healthy lung cells and could allow
for higher amounts of toxic drugs to be used to increase the number of
tumor cells killed, without causing unwanted side effects.

"While smart nanoparticles with unique features can be engineered in
various ways, systemic administration of these agents into the bloodstream often results in uncontrolled spread of the particles with only a few
of them reaching the interior of solid tumors. This has been a global
challenge hampering more wide-spread use of nanoparticle systems in the clinics," explains Darcy Wagner.

The study was led by first author Dr. Deniz Bo"lu"kbas, a postdoctoral
fellow working in Wallenberg Molecular Medicine Fellow at Lund University
and Associate Professor Darcy Wagner's research group. Wagner and her
team focus on designing new therapies for patients with lung disease by combining concepts from engineering, medicine, and cell biology.

"Direct administration of these nanoparticles into the blood vessels
of the lungs allowed us to restrict the accumulation of these particles
only in the lungs which eventually led to successful and selective tumor targeting," says Bo"lu"kbas.

ORVD of nanoparticles puts a new twist on a decades-old technique
called "isolated lung perfusion" which involves direct administration
of chemotherapeutic drugs into the blood vessels of the lungs. It has
been demonstrated to be surgically safe in patients with lung tumors by
various centers around the world, but chemotherapeutics had negative side effect on the healthy tissue neighboring the lung tumor. According to
Wagner and Bo"lu"kbas, this surgical approach combined with the features
of smart nanoparticles holds promise to overcome this previous limitation
and has potential as a new treatment.

"The development of this new approach is a significant step forward"in
the field of lung cancer treatment, say Bo"lu"kbas and his coauthors, but
"it is important to validate the therapeutic potential of this approach
to deliver specific chemotherapeutics and to explore the feasibility of
this approach in large animal models."

========================================================================== Story Source: Materials provided by Lund_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Deniz A. Bo"lu"kbas, Stefan Datz, Charlotte
Meyer‐Schwickerath,
Carmela Morrone, Ali Doryab, Dorothee Go"ssl, Malamati Vreka, Lin
Yang, Christian Argyo, Sabine H. Rijt, Michael Lindner, Oliver
Eickelberg, Tobias Stoeger, Otmar Schmid, Sandra Lindstedt,
Georgios T. Stathopoulos, Thomas Bein, Darcy E. Wagner,
Silke Meiners. Organ‐Restricted Vascular Delivery:
Organ‐Restricted Vascular Delivery of Nanoparticles for Lung
Cancer Therapy (Adv. Therap. 7/2020). Advanced Therapeutics, 2020;
3 (7): 2070016 DOI: 10.1002/adtp.202070016 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200715123132.htm

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