The Effective Combination between 3D Cancer Models and Stimuli-Responsive Nanoscale Drug Delivery Systems.

Federica Foglietta,Roberto Canaparo,Loredana Serpe

doi:10.3390/cells10123295

Federica Foglietta, Roberto Canaparo + Show 1 more

Open Access

https://doi.org/10.3390/cells10123295

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Journal: Cells	Publication Date: Nov 25, 2021
Citations: 14	License type: CC BY 4.0

Affiliation: University of Turin

Abstract

Stimuli-responsive drug-delivery systems (DDSs) have emerged as a potential tool for applications in healthcare, mainly in the treatment of cancer where versatile nanocarriers are co-triggered by endogenous and exogenous stimuli. Two-dimensional (2D) cell cultures are the most important in vitro model used to evaluate the anticancer activity of these stimuli-responsive DDSs due to their easy manipulation and versatility. However, some limitations suggest that these in vitro models poorly predict the outcome of in vivo studies. One of the main drawbacks of 2D cell cultures is their inadequate representation of the 3D environment’s physiological complexity, which sees cells interact with each other and the extracellular matrix (ECM) according to their specific cellular organization. In this regard, 3D cancer models are a promising approach that can overcome the main shortcomings of 2D cancer cell cultures, as these in vitro models possess many peculiarities by which they mimic in vivo tumors, including physiologically relevant cell–cell and cell–ECM interactions. This is, in our opinion, even more relevant when a stimuli-responsive DDS is being investigated. In this review, we therefore report and discuss endogenous and exogenous stimuli-responsive DDSs whose effectiveness has been tested using 3D cancer cell cultures.

Highlights

Three-dimensional (3D) cell cultures have acquired considerable amounts of interest over the last twenty years becoming a versatile tool, especially for cancer research, due to their intrinsic capacity to better mimic the tumor microenvironment (TME) complexity [1,2].Currently, the growth of 3D cell cultures can be generated using several protocols, which allows 3D models to be classified into two categories: scaffold- and non-scaffold-based approaches [3]
We have described the application of 3D models in the development of stimuli-responsive drug-delivery systems (DDSs) in order to understand whether this new in vitro approach might encourage the clinical translatability of these stimuli-responsive nanocarriers by improving their preclinical investigation
Spheroid models do not account for transport across the vascular endothelium, limiting their ability to represent the enhanced permeability and retention (EPR) effect, which is a key feature in the success of DDSs in cancer treatment

Summary

Introduction

Three-dimensional (3D) cell cultures have acquired considerable amounts of interest over the last twenty years becoming a versatile tool, especially for cancer research, due to their intrinsic capacity to better mimic the tumor microenvironment (TME) complexity [1,2].Currently, the growth of 3D cell cultures can be generated using several protocols, which allows 3D models to be classified into two categories: scaffold- and non-scaffold-based approaches [3]. Three-dimensional (3D) cell cultures have acquired considerable amounts of interest over the last twenty years becoming a versatile tool, especially for cancer research, due to their intrinsic capacity to better mimic the tumor microenvironment (TME) complexity [1,2]. The first requires an external support to be engineered to mimic the extracellular matrix (ECM), and this allows cells to anchor to the support, to proliferate, and migrate across scaffold interstices. Thanks to these characteristics, cells acquire typical in vivo tumor hallmarks, along with the specific distribution of an in vivo setting [4]. In non-scaffold-based platforms, tumor cells can aggregate and form so-called tumor spheroids.

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