Abstract
Over the past decades, research has made impressive breakthroughs towards drug delivery systems, resulting in a wide range of multifunctional engineered nanoparticles with biomedical applications such as cancer therapy. Despite these significant advances, well-designed nanoparticles rarely reach the clinical stage. Promising results obtained in standard 2D cell culture systems often turn into disappointing outcomes in in vivo models. Although the overall majority of in vitro nanoparticle research is still performed on 2D monolayer cultures, more and more researchers started acknowledging the importance of using 3D cell culture systems, as better models for mimicking the in vivo tumor physiology. In this review, we provide a comprehensive overview of the 3D cancer cell models currently available. We highlight their potential as a platform for drug delivery studies and pinpoint the challenges associated with their use. We discuss in which way each 3D model mimics the in vivo tumor physiology, how they can or have been used in nanomedicine research and to what extent the results obtained so far affect the progress of nanomedicine development. It is of note that the global scientific output associated with 3D models is limited, showing that the use of these systems in nanomedicine investigation is still highly challenging.
Highlights
Despite the significant advances in cancer therapy over the past decades, cancer remains the one of the major causes of death worldwide [1]
Other abbreviations: PGLA: poly(glycolide-co-lactide), Au: gold, ECM: extracellular matrix, pDNA: plasmid DNA, MSN WS2-HP Cluster Bomb: mesoporous silica nanoparticle (MSN) capped with tumor-homing/penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP), polyethylene glycol (PEG): poly(ethylene glycol), PEG-PCL: poly(ethylene glycol)-poly(ε-caprolactone), HDL: high density lipoprotein, Folic acid-CM-PFA/pDNA: nanoparticles decorated with folic acid-poly(ethylene glycol) and dual amino acid-modified chitosan complexed with DNA
In nanomedicine research, the efficiency is measured on 2D culture systems and, when positive results are obtained, research is often directly translated to in vivo animal models
Summary
Despite the significant advances in cancer therapy over the past decades, cancer remains the one of the major causes of death worldwide [1]. The most known examples are Doxil® and Abraxane®, for the delivery of doxorubicin and paclitaxel, respectively [7,8] In spite of this progress, promising results obtained in standard 2D cell culture systems often turn into disappointing outcomes in in vivo models. While 2D culture systems remain the most popular screening method used for drug development, researchers have started exploiting more complex 3D model systems to bridge the gap between the in vitro models and in vivo physiology of the human body. Despite the increased popularity of such complex 3D models, their application in the development and evaluation of drug nanocarriers remains limited and the majority of nanomedicine development is still performed on 2D monolayer cell culture systems. We aim to provide a guideline for researchers working in nanoparticles that wish to start using 3D cancer models for the development of nanocarrier-based cancer treatments
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