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

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.

Terminalia chebula Polyphenol and Near-Infrared Dye-Loaded Poly(lactic acid) Nanoparticles for Imaging and Photothermal Therapy of Cancer Cells

“…This could be due to minimal light penetration or a hypoxic microenvironment in the inner core. However, spheroids treated with P p IR NPs after NIR light irradiation exhibited more cell death from the inner core of the tumor toward the peripheral region when compared to cells treated with only NPs (Figure A) . These findings suggest that, for effective tumor targeting, the core region of the tumor should show the maximum cell death .…”

“…However, spheroids treated with PpIR NPs after NIR light irradiation exhibited more cell death from the inner core of the tumor toward the peripheral region when compared to cells treated with only NPs (Figure 6A). 47 These findings suggest that, for effective tumor targeting, the core region of the tumor should show the maximum cell death. 9 It helps to understand the cell signaling pathways that can induce metastasis, apoptosis, and resistance, which can be integral parts of combating cancer and taking preventive measures against health relapse.…”

Advances in the application of 3D tumor models in precision oncology and drug screening

“…Using tumor-targeted nanocarriers, such as liposomes, nanoparticles, or micelles, produces unique advantages for the delivery of antitumor drugs or genes, such as increasing the in vivo circulation time, increasing tumor site accumulation, and reducing toxicity to normal organs ( Campisi et al, 2012 ; Shin et al, 2013 ; Li et al, 2018 ; Carey-Ewend et al, 2020 ; Nii et al, 2020 ; Bartusik-Aebisher et al, 2021 ; Borodina et al, 2021 ; Bromma et al, 2021 ; Foglietta et al, 2021 ). RGD peptides are a kind of peptide that contain Arg-Gly-Asp sequence, internalizing RGD peptide (iRGD) can increase drug penetration into extravascular tumor tissue.…”

Recent Advance in Tumor Microenvironment-Based Stimuli-Responsive Nanoscale Drug Delivery and Imaging Platform

“…Nanomaterials can be produced into a variety of spatial structures, morphology, forms, and surface modification based on their intrinsic thermal, electrical, magnetic, and optical physical properties. Nanomaterial is widely used as a theranostic agent in PTT (photothermal therapy) (Huang et al, 2021), PDT (photodynamic therapy) (Bharathiraja et al, 2018;Wu et al, 2021), CDT (chemodynamic therapy) (Wang et al, 2022;Yang et al, 2022), and NDDS (Bai et al, 2021;Foglietta et al, 2021) to overcome the limitations of standard cancer treatments.…”