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Targeted anti-cancer drug delivery system.

Country of Origin: Slovenia
Reference Number: TOSI20170731001
Publication Date: 1 August 2017


A Slovenian research institution has developed a specific bio-molecular drug delivery system using a selective cathepsin inhibitor as a guiding molecule towards cancer sites. The invention solves the problem of safely and accuracy of drug delivery to the cancer target site. The researchers seek research cooperation, license or a joint venture agreements with partners interested in participating with the pre-clinical studies, manufacturing scale-up or phase-1 clinical trials.


One of the characteristics of tumour cells and tumour stroma cells is their secretion of the proteolytic enzymes such as cathepsins, which actively promote tumour growth and are therefore amenable as targets for targeted delivery of anti-cancer drugs. 

The invention is bio-molecular drug delivery system with a specific cathepsin-B inhibitor linked to a highly bio-compatible liposomal nano-carrier via lipid tail and which enables specific targeting of cathepsins in the tumour microenvironment, and therefore bringing the liposomomal nanocarrier containing the drug payload (eg. doxorubicin), to the target site. Liposome based drug delivery system enables reduction in dosages and systemic toxicity with increased efficiency of anti-cancer drugs which leads to more efficient and less costly treatments. Successful functioning of the system has been demonstrated both in vitro on various cell cultures and in vivo on mouse cancer model. In vitro experiments on cells showed that encapsulated doxorubicin in liposomes with linked cathepsin-B inhibitor was 22 fold more potent in killing cells compared to only liposome encapsulated doxorubicin. While in vivo data confirmed increased accumulation of liposomes with linked cathepsin-B inhibitor in tumours while there was no accumulation in healthy tissue.

The technology is applicable for targeted delivery of both anti-tumour and anti-inflammatory drugs to pathological sites. It enables to deliver both water soluble and insoluble compounds to the target site due to the liposome structure with lipid layer and hydrophilic core.
Apart from treatment, the technology is also applicable for detection purposes (for example, by specific delivery of a fluorescent marker or magnetic resonance imaging (MRI) contrast agent to a tumour site), and was confirmed using encapsulated Gadolinium (Gd) with linked cathepsin-B inhibitor on tumour bearing mice, which resulted in signal enhancement, prolonged retention and elimination.

The researchers are among the world's leading experts in the field of proteases (primarily cysteine cathepsins) and their regulation of physiological processes in normal and pathological conditions, including cancer, and inflammatory associated diseases, and have extensive knowledge and expertise in cell biology, proteomics, animal cancer models and in-vivo imaging techniques. The researchers filed number of patent on drug delivery systems on international level, have many international collaborations and have participated in several International and EU projects among which, EU project FP7 that was focused on developing drug delivery system for oral and ocular application. They published over a hundred articles in high-impact scientific journals.

Partners are sought to participate with the finalisation of the pre-clinical and/or clinical trials. Most suitable partners are already involved in biotechnology and pharmaceutical industry or are investors.

The types of cooperation preferred are as:
- joint venture for the finalisation of the pre-clinical trials and/or phase-1 clinical trials
- license agreement to implement the proposed technology
- research cooperation agreement for the finalisation of the pre-clinical trials and/or phase-1 clinical trials

Advantages and Innovations

A number of drugs exhibit major harmful side effects or are inefficient because of low bioavailability. This invention solves the problem by safely and accurately delivering the drug to its target site.
Drug toxicity is reduced using a liposome-based delivery system. The drug is guided directly to the tumour tissue using liposomes with bound inhibitors of cathepsins, which are characteristically secreted by tumour cells.
The use of liposomes as drug delivery systems is safe as liposomes are biologically inert, natural occurring particles in the human body and biodegradable; use of liposomes as drug carriers is common, and approved by the U. S. Food and Drug Administration. Using targeted delivery, therapy is made more efficient, thereby reducing the required dosage for the same effect, which leads to reduced treatment costs. Advantage in the production of the invented drug delivery system is that it can be done by standard biochemical procedures and is compatible with most R&D institutions, while it is substantially cheaper compared to the antibody based drug delivery system or drug-conjugates. The invention was tested in-vitro and in-vivo. In-vitro analysis of the system showed 20-fold higher tumour cell killing capacity of encapsulated doxorubicin (i.e. requires 20-fold lower drug quantity for the same effect), compared to passive drug delivery (i.e Doxil). While in-vivo imaging on tumour bearing mice using MRI and encapsulated Gadolinium in liposomes bound with inhibitors showed increased and prolonged signal intensity compared to background as well as excretion from the system without accumulation in healthy tissues. Since liposomes are inert, this drug delivery system enables minimisation of side effects of the drugs and targeted delivery exclusively to tumour cells, increasing drug efficiency and patients' survival.

Stage Of Development

Concept stage

Requested partner

Industry partners or investor active in the fields of biotechnology and pharmaceutical industry, with option of own manufacturing capacities are sought for the finalisation of the pre-clinical and clinical trials in case of medicinal implementation of the offered technology. 

In case of a
- joint venture agreement the partner is expected to offer knowledge and financing,
- license agreement the partner is expected to purchase rights for the use of the patent-protected solution
- research cooperation agreement with partners with relevant know-how, the capacity, and accreditation to carry out pre-clinical studies and/ or scale-up the manufacturing to the industrial scale.

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