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Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18, led by Prof Antoni Villaverde have published the article “Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin” at SMALL journal.

Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4+ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery.

See article: https://doi.org/10.1002/smll.201800665

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NANOLIGENT, the first drug designed to eliminate metastases stem cells

NANBIOSIS researchers have developed a nanomedicine for the treatment of metastases by the selective elimination of tumor stem cells. It is a system based on nanoparticles that transport a chemotherapeutic drug and release it into cancer cells.

The research team, led by Esther Vázquez and Antonio Villaverde, Strategy Director of NANBIOSIS U1. Protein Production Platform (PPP), in the IBB-UAB, and Ramon Mangues, Scientific Director of NANBIOSIS U18. Nanotoxicology Unit, in the Sant Pau Hospital, have already created a prototype of the drug and have conducted in vivo trials in animal models of colorectal cancer. They have demonstrated their effectiveness, selective biodistribution and low toxicity.

To promote the development of the drug towards the clinic, the reserachers have created Nanoligent a start-up company, based in Barcelona, led by Manuel Rodríguez, a professional with experience in the field of investment and the creation and growth of biotech companies. The technology is patented in Europe and USA and has been licenced to Nanoligent

The therapy created by the researchers is aimed at blocking the development of metastasis, mainly of colorectal cancer, through new strategies aimed at certain cell types. It consists of a new drug administration system based on protein nanoparticles that selectively conduct the therapeutic agent in tumor cells. The drug acts only on cancer cells, because it is based on the specific interaction between a protein present in the nanoparticle and a cellular receptor (CXCR4), which is overexpressed in tumor cells. “This interaction is crucial, because it allows attacking only tumor cells and not healthy cells, thus avoiding secondary effects derived from classical chemotherapy,” emphasizes Antonio Villaverde.

The CXCR4 receptor is overexpressed in many types of tumors, so that “this technology can be directed to the treatment of different types of neoplasms in addition to colorectal cancer and derived metastases, such as lymphoma, leukemia or endometrial cancer, in animal models already available to the group of Sant Pau “, comments Ramon Mangues. In addition, nanoparticles are compatible with a huge variety of possible drugs and therefore they become highly versatile vehicles that can carry a wide range of therapeutic molecules.

“There is an urgent need for more effective and personalized treatments for cancer. The toxicity and the lack of efficacy of conventional drugs are pushing alternative experimental strategies directed and designed to achieve only defined cell types. Nanoparticles, thanks to their capacity for penetration, dissemination and functionality, offer a promising nanomedical landscape to create new drugs,” explains Esther Vázquez.

In this direction, the technology of Nanoligent opens a new door in anti-pelagic therapy, as it allows to design a treatment with greater cellular specificity than that of existing treatments, while offering greater biosecurity and biodegradability and lower toxicity,” he said. Antonio Villaverde points out.

Currently, there are no drugs in the market that selectively eliminate metastatic stem cells. Although Nanoligent technology is still under development, researchers say they have a lot of potential and consider that it could have a high clinical impact as regulatory trials are overcome.

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