Page 106 - Demo

1. INTRODUCTION The recent progresses in nanomedicine and three-dimensional (3D) in vitromodelling fields have opened new avenues for the use of preclinical 3Dplatforms to evaluate the therapeutic efficiency of nanoscale treatments,paving the way for the discovery of potential new therapies for humanmalignancies. Advances in targeted systems for the selective delivery of therapeuticagents have revolutionized cancer research and medicine, owing to theirability to surpass the limitations of conventional cancer treatmentapproaches which often results in low accumulation in tumor tissue andconsequent inefficiency, as well as in significant side effects owing to itsnon-specific role, affecting both healthy and malignant tissues.Nanotherapies represents one of the most promising advances in oncology,offering the possibility to therapeutics delivery in a targeted manner,promoting the enhanced efficacy of the treatment and reducing sideeffects. Cancer nanotherapies often rely on the use of nanoparticlesdesigned to be between 1-100 nm, promoting effective interactions withmalignant cells at the molecular level. A number of efforts have beenconducted to promote the therapeutic role of nanotherapies by engineeringnanocarriers comprising chemotherapeutic drugs, nucleic acids andimmunotherapeutic agents. Such an approach allows to take advantage ofthe enhanced permeability and retention effect of nanoparticles, ensuringtheir accumulation in tumor site, thus minimizing exposure to healthytissues. Despite their potential, such strategies still face several challengesthat will be discussed later in this chapter. As nanotherapies evolve, the increasing demand for more reliable andpredictive preclinical tumor models that accurately emulate human tumorsmicroenvironment (TME) has become apparent. Conventional oversimplifiedtwo-dimensional (2D) cell cultures fail to recreate the complexity of nativetumors, leading to poor translational outcomes. From this standpoint, 3Din vitro models emerged as alternative preclinical platforms able to moreaccurately emulate human TME, allowing closely resembling key tumorhallmarks, cell-cell/cell-matrix interactions and 3D spatial cellularorganization, thus providing a promising platform for testingnanotherapeutics approaches under a more physiological-relevant andrealist scenario.Overall, the combination of nanotherapy and 3D in vitro models isopening up new opportunities in cancer research and drug development.This chapter explores the most recent advances in exploring 3D models forscreening nanotherapeutics that are designed for cancer therapy.104Potential of 3D tumor models for nanotherapies pre-clinical screeningVitor M. Gaspar1, Jo%u00e3o F. Mano, et al.