ABSTRACT

Organoids are three-dimensional multicellular structuresthat recapitulate the differentiated cell-specific morphological and functional composition featuring tissues and organs of their origin.These miniature structures can be engineered to elucidate the role of various factors in developmental and disease mechanisms. Particularly, one of the major focuses of organoid model systems is to study the interactions between mechanical cues or stresses and micro-environment to mimic in vivo tissue/organ structures. However, most of the current approachesin vitro depend on mechanical changes introduced throughthe matrix, which lack important specificities likedirection and positionas ofin vivo scenarios. Incidentally, nanoparticles (NPs) are efficiently internalised by the cells and canreadily disperse through extracellular matrices. Thus, these moieties can be targeted formatrix engineeringby inducing mechanical perturbations in organoids and tissues. On the other side, nanoparticle-based drug delivery systems are extensively explored due to their efficient internalisation into cells. However, these moieties get easily cleared from the system without having the desired persistent effects. To this end, organoidscan potentially serve as trojan horses for drug delivery through nanoparticles. Additionally, organoids are made up of all major types of cells in an organ thus potentially offering biologically more compatible modality limiting pharmaceutical toxicity. Inthis chapter, we aim to summarise (a) the possible translational utility of nanoparticles towards modulating matrix and tissue mechanics, as mechano-transductor in multicellular model systems,and (b) organoids as biologically compatible systems assisting nanoparticle-based drug delivery.