News

head uk2

How chitosan can help against breast cancer

Breast cancer will affect one in eight women during their lifetime. Especially metastatic breast cancer has a low survival rate. In this article, we present a review of current research on the use of chitosan in breast cancer therapy and diagnostics.

Tags: drug delivery, chitosan, nanoparticles, breast cancer, diagnostics

CHITOSAN: A VERSATILE BIO-PLATFORM FOR BREAST CANCER THERANOSTICS

Madamsetty, V. S.; Tavakol, S.; Moghassemi, S.; A. Dadashzadeh, J. D. Schneible, I. Fatemi, A. Shirvani, A. Zarrabi, F. Azedi, A. Dehshahri, A. A. Afshar, K. Aghaabbasi, A. Pardakhty, R. Mohammadinejad, P. Kesharwani, Chitosan: A versatile bio-platform for breast cancer theranostics, Journal of Controlled Release, Volume 341, 2022, Pages 733-752, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.12.012

Breast cancer (BC) is a neoplastic, frequent disease of women in developed or developing countries the high mortality rates mainly due to metastasis to the lung, brain or liver. One in eight women will be affected during their lifetime. BC is treated with drugs, e.g. in the form of chemotherapy, immunotherapy or hormone therapy, radiotherapy, surgery or a combination of these. However, no ideal method has yet been found. Drug therapy often has severe side effects, while surgery and radiotherapy have low specificity and high invasion. Overall, metastatic breast cancer has a low 5-year survival rate of about one quarter of affected women.

Great efforts are therefore being made to develop new therapies with fewer side effects and low invasion. Promising approaches are in nanomedicine e.g. drug delivery systems or nanoparticles to reduce tumor growth and metastasis. In this context, natural polymers such as chitosan are particularly interesting due to their good biocompatibility and biodegradability. Chitosan is in focus because it can be easily modified by its free amine groups and thus the macroscopic properties can be specifically changed. In the treatment of BC there are already some approaches how chitosan could improve therapies and diagnostics.

CHITOSAN IN DRUG DELIVERY SYSTEMS

  • Chitosan-based nanoparticles (CS-NPs) are able to overcome mucosal barriers and release drugs in a delayed manner
  • Studies on chitosan-based drug delivery of e.g. tamoxifen, doxorubicin or curcumin
  • Tamoxifen:
    • Non-steroidal anti-estrogen, used to treat advanced BC disease post-menopausal women, palliative treatment of pre-menopausal women
    • Oral administration shows low efficacy and significant side effects, however, promising results with CS-NPs
    • Layer-by-layer multi-alginate/chitosan complex NPs enable local and concentrated drug release
    • Improved bioavailability and antitumor effects of tamoxifen with modified α-tocopherol succinate-g-carboxymethyl CS-NPs
    • NPs loaded with tamoxifen showed lower IC50 values against MCF7 cells than the unbound drug
  • Doxorubicin (DOX)
    • Often used chemotherapeutic agent for BC that has serious side effects without nanoformulations
    • Magnetic CS nanocarriers for pH-dependent targeted drug delivery, including uptake of this NP in DOX-resistant cells
    • Injectable on co-crosslinking chitosan-based thermosensitive hydrogel with 188Re and DOX to prevent recurrence of revascularization after masectomy
  • Curcumin (1,7-bis-(4-hydroxy-3-methyloxyphenyl) -1,6-hepta-diene-3,5-dione)
    • Exceptional antitumor properties, inhibits cancer proliferation and apoptosis, influence on expression and activity of cytokines, enzymes, transcription factors, cell survival genes
    • Problem: insoluble in water and unstable → improvement by nanotechnology
    • pH-sensitive chitosan zinc oxide NPs to improve antibacterial and antitumor properties of curcumin
    • Chitosan lipoic acid NPs to improve curcumin transport to BC cells, thereby improving accumulation in cancer cells and enhancing killing efficiency

CHITOSAN IN GENE DELIVERY SYSTEMS

  • Promising due to interaction between negatively charged nucleic acids and positively charged chitosan
  • Possibility of inactivating pathogenic genes that play a role in the invasion of tumor cells via gene transfer, but risk of also affecting healthy cells → active or passive tagging important
  • Option: encapsulation or functionalization with chitosan
  • Low molecular weight chitosan (LMWC, Mw approx. 2000 Da) is well taken up by cells, but only low release of nucleic acids, poor gene silencing potential
  • Medium molecular weight chitosan (20 000 - 80 000 Da) most efficient, compromise between good cell uptake and nucleic acid release
  • Improvement of chitosan solubility by functionalization with e.g. lactate, polyhistidinarginine or thiolated glycol
  • transfer of miRNA and siRNA or DNA by binding to surface or entrapment in CS-NPs

CHITOSAN FOR GENE AND DRUG CO-DELIVERY

  • Enhancement of antitumor properties of gene delivery by co-delivery with drug
  • Example: CS-NPs with anti-mucin1 adaptamer encapsulated with GF-1R siRNA and docetaxel as chemotherapeutic agents resulted in better cellular uptake and higher cancer cell mortality
  • Combined gene and drug delivery showed higher potential in BC control as free drug and nucleic acids, as well as pure CS-NPs with drug or nucleic acids

CHITOSAN IN BC BIOIMAGING AND THERANOSTICS

  • CS-NPs interesting for bioimaging of cancer cells by magnetic and optical features
  • Examples:
    • gold nanoparticles coated with glycolchitosan → Cancer cell detection through photoacoustic contrast properties, accumulation of nanoparticles inside cancer cells leads to increase of temperature inside cells which can be detected
    • N,N,N-trimethyl chitosan coated by magnetic nanoparticles with DOTA or 68Gallium as radioactive chelator for imaging BC cells in PET/MRI scanning

Summary and Future Prospects: Overall, chitosan shows great potential in BC therapy and diagnostics, e.g., in nanoparticles for gene or drug delivery. However, only five of the 114 clinical trials on clinicaltrials.gov deal with chitosan in therapy against breast, lung or prostate cancer. Particularly inhomogeneous chitosan and problems with scale up complicate the development of therapeutics with chitosan. The authors of the review see promising approaches in the development of mucosal vaccines. Further potential for optimization would also lie in improving the physiochemical properties of chitosan. Link to article: https://pubmed.ncbi.nlm.nih.gov/34906606/

Congress and fairs

Meet us in person 2022:

  • EUCHIS, 2022
  • CPHI 2022
  • Medica 2022
  • Asia Pacific Chitin and Chitosan Symposium, 2022, South Korea

To arrange an appointment please contact Katja Richter via sales(at)medical-chitosan.com

Contact

  • Heppe Medical Chitosan GmbH
    Heinrich-Damerow-Strasse 1
    06120 Halle (Saale)
    Germany
  • Tel.: +49 (0) 345 27 996 300
    Fax: +49 (0) 345 27 996 378
  • sales@medical-chitosan.com

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.