La Verde, Giuseppe (2022) Effects of radiotherapy on the mechanical microenvironment of breast cancer cell to improve HA-coated NPs delivery. [Tesi di dottorato]

Anteprima

Testo La_Verde_Giuseppe_xxxv.pdf Download (7MB) | Anteprima

Abstract

Managing the medical treatment of widespread diseases, such as cancer, poses both a scientific and a health challenge. However, in systemic therapies as chemotherapy, failure is usually caused by the intrinsic biological nature of cells among which multidrug resistance (MDR); on the other hand, it promotes the development of alternative approaches such as targeted therapy and nanomedicine. Also radiotherapy, a localized treatment, is constantly improving: the irradiations are tailor-made for each individual case, guaranteeing the maximum dose on the tumor and saving the surrounding ones as much as possible. What follows, therefore, is that the study for treatment plans optimization plays a fundamental role in the success of the therapy. This PhD project investigated the effects of ionizing radiation, at the doses used in traditional radiotherapy (2 and 10 Gy), on the biophysical properties of breast cancer cells (MDA-MB-231, classified as triple negative, highly metastatic). From mechanobiological point of view, the cytoskeleton and extracellular matrix alterations result in a reduction of metastatic processes. A further implication is that they could represent a strategy to increase targeted therapy, bypassing the cancer cells MDR. The work is organized in three parts, corresponding to the thesis chapters and which concerned: (i) study of cellular microenvironment with a detailed biophysical characterization of the effects of radiation on spreading, migration and expression of proteins that influence the nuclear structure; (ii) formulation and stability measurements of nanoparticles functionalized with hyaluronic acid, as a therapeutic tool in view of clinical application; (iii) study of internalization of cells irradiated with doses typical for radiotherapy. The results encourage a combination radio- chemo-therapy in order to exploit ionizing radiation both to reduce the progression of metastases and to promote drug delivery.

Downloads

Actions (login required)

Modifica documento