Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

carbohydrates

It is fascinating how similar concepts can be used for entirely different purposes in drug delivery: while we use amphiphilic cyclodextrin for packaging oligonucleotides in the GENEGUT project, Erem Bilensoy and her team at Hacettepe University created camptothecin-loaded nanoparticles to treat colon cancer. The overall findings indicated that the strategy of orally targeting anticancer drugs such as CPT with positively charged poly-β-CD-C6 nanoparticles to colon tumors for local and/or systemic efficacy is promising.

Dr. SEDAT ÜNAL (PharmD/PhD), Gamze Varan, Yeşim Aktaş

See the full article here

Targeting galectin-driven regulatory circuits in cancer and fibrosis

carbohydrates, drug discovery,

Comprehensive summary from Gabriel Rabinovich Karina V. Marino Alejandro Cagnoni Diego Croci Russo (University of Buenos Aires) on the array of galectin-targeted strategies, including small-molecule carbohydrate inhibitors, natural polysaccharides and their derivatives, peptides, peptidomimetics, and biological agents reviewing the results of clinical trials that aim to evaluate the efficacy of galectin inhibitors in patients with idiopathic pulmonary fibrosis, nonalcoholic steatohepatitis, and cancer.

See the full article on nature.com.

Treatment of cancer

carbohydrates, , , ,

This patent on CRLX-101, an experimental approach using camptothecin (CPT) to cancer chemotherapy, reminded us of a wonderful idea from Mark Davis (Caltech). In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolyzed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect. As a result, the anticancer drug is enhanced and retained in the tumor tissue.
The new patent from Ellipses Pharma proposes novel applications dominantly in rectal cancer.
Amato Giaccia, Hanna Sanoff, Joel Tepper

Incorporation of Hydrophilic Macrocycles Into Drug-Linker Reagents Produces Antibody-Drug Conjugates With Enhanced in vivo Performance

Today's cyclodextrin, ,

Antibody-drug conjugates (ADCs) have begun to fulfill their promise as targeted cancer therapeutics with ten clinical approvals to date. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers. In this paper from Abzena, the effect of incorporating hydrophilic macrocycles like cyclodextrin into reagent structures on the in vitro and in vivo behavior of ADCs.

Nick Evans, Ruslan Grygorash, Nicolas Camper, Mark Frigerio, Matthew Bird et al

See the full article here

Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer

drug delivery, , ,

We are proud to share Milo Malanga‘s most recent collaboration paper with Hacettepe University on creating nanoplexes via cationic cyclodextrin polymer, 5-Fluorouracil, and Interleukin-2 based on the opposite charge interaction of macromolecules without undergoing any structural changes or losing the biological activity of Interleukin-2. In the colorectal tumor-bearing animal model, survival rate, antitumor activity, metastasis, and immune response parameters were assessed using a cyclodextrin derivative, which was found to be safe based on the ALT/AST levels in healthy mice.

Histomorphometric analysis showed that the groups treated with the nanoplex formulation had significantly fewer initial tumors and lung foci when compared with the control. The dual drug-loaded nanoplex could be a promising drug delivery technique in the immunochemotherapy of colorectal cancer.

Safiye Akkın, Gamze Varan, Anıl Işık, Petek Korkusuz, Erem Bilensoy et al.

See the full article here

Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

drug discovery, ,

Last week we shared applications of cyclodextrin in various types of cancer, and a discussion was triggered byTamas Sohajda about “why is it always HPBCD that is studied.” In this paper from Kumamoto University, JAPAN, by Keiichi Motoyama, Mannose-methyl-β-cyclodextrin is applied to suppress tumor growth by targeting colon cancer cells and tumor-associated macrophages.

See the full article here.

Hydroxypropyl-β-cyclodextrin inhibits the development of triple-negative breast cancer by enhancing antitumor immunity

drug development, ,

After sharing news on treating lymphedema, we came across another potential therapeutic use of cyclodextrin. In this preprint from Hefei University of Technology and Emory University authors demonstrate that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inhibited the growth and metastasis of triple-negative breast cancer (TNBC) both in vitro and in vivo, although the underlying mechanisms are unclear.
Cholesterol supplementation can attenuate HP-b-CD-inhibited TNBC growth and metastasis both in vitro and in vivo. In vivo, HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved the exhaustion of CD8+ T cells via reducing endoplasmic reticulum (ER) stress and immune checkpoint molecules. Additionally, HP-β-CD inhibited the recruitment of tumor-associated macrophages to the TME by reducing the CCL2-p38MAPK-NF-kB axis. HP-β-CD also inhibited the epithelial-mesenchymal transition (EMT) of TNBC cells mediated by transforming the growth factor-b (TGF-b) signaling pathway.
In summary, the data in the current study suggest that HP-β-CD effectively inhibited the proliferation and metastasis of TNBC and melanoma, highlighting HP-β-CD may be a potential general antitumor clinical drug.

See the full article here

The authors found that HP-b-CD inhibits the proliferation and metastasis of TNBC by reducing cholesterol levels. HP-b-CD promotes T cell recruitment to the TME and improves CD8+ T cell exhaustion. Additionally, HP-b-CD inhibits TAMs accumulation.