Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Nanomedicine -- Targeting cancer cells with sugars

Nanocarriers binding the mannose receptor. Picture: C Hohmann/NIM
Nanocarriers binding the mannose receptor. Picture: C Hohmann/NIM

Abstract:
Globally, cancer is the second leading cause of death, also because the efficiency of chemotherapeutics is inadequate due to poor delivery to the tumor. NIM scientist Prof Olivia Merkel and her team develop targeted nanocarrier systems to increase the delivery rates of therapeutic formulations and their specific uptake into the target cells.

Nanomedicine -- Targeting cancer cells with sugars

Munich, Germany | Posted on May 14th, 2018

In the treatment of cancer, there are still several limitations. Especially the delivery of sufficient amounts of active chemotherapeutic drug is difficult. After the conventional intravenous administration, the therapeutic formulation faces some hurdles before reaching the target site. In most cases, the blood circulation time of the active compound is rather short, and a substantial amount of the remaining active drug accumulates in non-target tissues and leads to the known unpleasant and unwanted side-effects in patients.
Therefore, the group of Professor Opens external link in new windowOlivia Merkel focuses on the development of stable and targeted nanocarrier formulations and alternative administration routes. One approach is the targeting of specific sugar receptors expressed on several cancer cells, the mannose and mannose-6-phosphate receptors. The new publication in Opens external link in new windowAdvanced Healthcare Materials provides a nice overview of the field and presents first results of a new approach tested in the Merkel Lab.
Mannose for cancer-cell specific drug delivery
Every human cell has a cell type-specific repertoire of surface receptors to assure the uptake of needed supplies. Due to their high demand in nutrients for rapid proliferation, cancer cells have a very high affinity for carbohydrate molecules compared to normal cells. Several tumor cells express, for example, mannose receptors and mannose-6-phosphate receptors for efficient endocytosis of these sugars, which are used for intracellular energy synthesis.
Hence, mannose has high potential as cancer cell-specific ligand for the targeted delivery of (chemo)therapeutic nanocarriers. The ‘lock and key principle’ describes the binding of such functionalized nanocarriers to the tumor cells: the mannose or mannose-6-phosphate receptors on the cell surface present the lock and the mannose ligand on the nanocarrier the matching key. After binding, the whole complex gets endocytosed. This could be visualized as inverse budding: A cell membrane coated vesicle engulfing the area with the ligand-receptor complex buds inwards into the cytosol.
“In our own experiments, we could show a significantly increased uptake of mannosylated carriers over non-modified particles,” Merkel explains. “The mannose receptor-mediated endocytosis enables the active uptake of (drug-)loaded nanocarriers specifically bound to tumor cells.”

Immunotherapy and gene-therapeutic approach
Expression of mannose receptor on the surface of antigen-presenting cells (APCs) opens another route for tumor therapy. APCs are the immune cells inducing an immune response by activating the respective lymphocytes (‘white blood cells’), cells directly attacking the target and developing the memory cells for a long-lasting defense. On the contrary, the mannose-6-phosphate receptor can also act as tumor suppressor and is discussed in detail as a new target.
Nanocarrier formulations for APC-targeting can be loaded with nucleic acids (‘gene-therapy’) coding for specific genes or an RNA-fragment mixture. Upon successful mannose receptor-mediated delivery to the APCs, those tumor antigens will be presented to lymphocytes and induce a rapid, cancer cell-specific immune response. Such immune cell-based therapeutic approach is called immunotherapy. In addition, this activation of the immune system could lead to a long-lasting anticancer response, often described as cancer vaccination and relapse prevention with professional APCs.

Advantages of nanocarriers
Functionalized nanocarriers encapsulating chemotherapeutics provide several advantages over conventional drug preparations. The loading into the carrier improves solubility of several drugs and acts stabilizing and shielding. Therefore, it highly increases the bioavailability due to extended blood circulation times compared to free drug.
The active targeting via surface ligands increases the specificity to cancer cells and the local delivery efficiency of active drug, as well as the stimulation APCs for innovative immunotherapy. In addition, such approach could help to overcome the dose-limiting off-target delivery of conventional chemotherapy, while even reducing the amount of administered drug.
Besides the capacity for loading with chemotherapeutics, nanocarriers can be (co-)loaded with imaging probes, for instance, facilitating non-invasive localization of tumor tissue and metastases. Formulations co-encapsulating both, therapeutics and diagnostic probes, are also called ‘theragnostics’.

Publication:
Mannose and Mannose-6-Phosphate Receptor-targeted Drug Delivery Systems and their application in Cancer Therapy.
Vedove ED, Costabile E, Merkel OM. Adv Health Mat 2018, Opens external link in new windowdoi:10.1002/adhm.201701398

####

For more information, please click here

Contacts:
Luise Dirscherl

49-089-218-03423

Prof Dr Olivia Merkel
Department of Pharmacy
Pharmaceutical Technology and Biopharmacy
Ludwig-Maximilians-Universität München
Butenandstraße 5-13, Building B
81377 Munich
Germany
Phone: +49 (0)89 2180 77025
emailolivia.merkel(at)lmu.de

Copyright © Ludwig-Maximilians-Universität München (LMU)

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Switching with molecules: Molecular switch will facilitate the development of pioneering electro-optical devices May 25th, 2018

Tunable diamond string may hold key to quantum memory: A process similar to guitar tuning improves storage time of quantum memory May 24th, 2018

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

2018 Kavli Prizes in Astrophysics, Nanoscience, and Neuroscience to be Announced Live on May 31: Live announcement at the Norwegian Academy of Science and Letters to be streamed live at World Science Festival Event May 24th, 2018

Cancer

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Elastic microspheres expand understanding of embryonic development and cancer cells May 15th, 2018

Results To Date Of Keystone Nano’s Ceramide Nanoliposome Clinical Testing May 7th, 2018

Nanobiotix and Weill Cornell Medicine Partner on Pre-Clinical Research Inbox x May 3rd, 2018

Possible Futures

Switching with molecules: Molecular switch will facilitate the development of pioneering electro-optical devices May 25th, 2018

Tunable diamond string may hold key to quantum memory: A process similar to guitar tuning improves storage time of quantum memory May 24th, 2018

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

'Spooky action at a distance': Researchers develop module for quantum repeater May 23rd, 2018

Nanomedicine

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

Elastic microspheres expand understanding of embryonic development and cancer cells May 15th, 2018

NanoBio Announces Corporate Name Change to BlueWillow Biologics and Closes $10M Series A Financing: Move Reflects Focus on Advancing Several Intranasal Vaccines to Human Studies May 9th, 2018

Discoveries

Switching with molecules: Molecular switch will facilitate the development of pioneering electro-optical devices May 25th, 2018

Tunable diamond string may hold key to quantum memory: A process similar to guitar tuning improves storage time of quantum memory May 24th, 2018

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

'Spooky action at a distance': Researchers develop module for quantum repeater May 23rd, 2018

Announcements

Switching with molecules: Molecular switch will facilitate the development of pioneering electro-optical devices May 25th, 2018

Tunable diamond string may hold key to quantum memory: A process similar to guitar tuning improves storage time of quantum memory May 24th, 2018

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

2018 Kavli Prizes in Astrophysics, Nanoscience, and Neuroscience to be Announced Live on May 31: Live announcement at the Norwegian Academy of Science and Letters to be streamed live at World Science Festival Event May 24th, 2018

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

Switching with molecules: Molecular switch will facilitate the development of pioneering electro-optical devices May 25th, 2018

Tunable diamond string may hold key to quantum memory: A process similar to guitar tuning improves storage time of quantum memory May 24th, 2018

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

'Spooky action at a distance': Researchers develop module for quantum repeater May 23rd, 2018

Nanobiotechnology

Remote control of transport through nanopores: New study outlines key factors affecting the transfer of molecules through biological channels May 24th, 2018

New blood test rapidly detects signs of pancreatic cancer May 17th, 2018

NanoBio Announces Corporate Name Change to BlueWillow Biologics and Closes $10M Series A Financing: Move Reflects Focus on Advancing Several Intranasal Vaccines to Human Studies May 9th, 2018

Nanoscale measurements 100x more precise, thanks to improved two-photon technique May 8th, 2018

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project