The extensive development of materials as potential drug delivery systems has emerged from the need for less invasive treatment of malignant diseases. The chemotherapy is commonly used method for treating the osteosarcoma, type of a bone tumour that affects children and young adults. The standard procedures are based on intravenous or oral administration of antitumor drug that inevitably affects the whole body before reaching the infected tissue. Consequently, antitumor drug also interacts with healthy organs and tissues increasing the risk of toxicity and adverse drug effects. Arising new strategy for improved treatment is the encapsulation of drug within adequate carrier for controlled release under specific stimulus. This project brings forth the development of smart antitumor drug carriers based on chitosan modified with therapeutic ions: copper, zinc, boron and phosphate ions. In our previous studies, we have proved the versatility of chitosan-based materials as scaffolds that significantly support bone formation from stem cells culture. The proposed investigation is a logical continuation on the improvement of functionality of biocompatible materials in form of delivery carriers for targeted osteosarcoma treatment. The main research focuses on: 1) smart drug delivery systems as microspheres suitable for injection; 2) highly porous scaffolds as drug and therapeutic carriers for tissue regeneration; 3) materials modification by calcium phosphates to enhance the antitumor efficiency; 4) in vitro biological validation of prepared materials on healthy and tumour cells. We expect the synergic activity of antitumor drug (doxorubicin) and copper, zinc and phosphate ions in suppressing the grow th of osteosarcoma cells, as well as improved efficacy without affecting the surrounding healthy tissue. Furthermore, we expect dual functionality, antitumor and therapeutic, of boron modified scaffolds in a way of inducing the vascularisation and neotissue growth.

The main objective of this project is to develop biocompatible materials as antitumor drug and therapeutic ions carriers for targeted osteosarcoma treatment. The principal investigation is focused on: 1) development of injectable less invasive drug delivery system for osteosarcoma treatment; and 2) development of dual functional carriers with antitumor and therapeutic efficacy for tissue regeneration. Due to high complexity of the project, investigation is divided into four work packages:

a) Synthesis and characterisation of smart drug and therapeutic metal ions delivery systems as microspheres suitable for injection;

b) Synthesis and characterisation of highly porous scaffolds as drug and therapeutic ions carriers for tissue regeneration;

c) Modification of microspheres and scaffolds by phosphate ions to enhance the antitumor efficiency;

d) In vitro biological validation of prepared materials on healthy cells and complex 3D tumour spheroids as in vivo-like models.