Table 3.
Exogenous stimuli-responsive DDSs in 3D cancer models.
| Exogenous | Stimuli | 3D Model | Drug Delivery Systems (DDSs) | Main Results | References |
|---|---|---|---|---|---|
| Light | Human bladder (T24) spheroids | A cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug and the photosensitizer chlorin e6 (Ce6) loaded into NPs (poly(OEGMA)-PTX@Ce6) | Ce6 released into the T24 spheroids and then light irradiated produced ROS. The PTX was also released by cathepsin B, determining anticancer effect | [58] | |
| Rat C6 glioma cell line (C6 MCS) | Targeted Micellar Nanoprobe (TMNP) with exceptionally high encapsulation efficiencies of a hydrophobic drug simvastatin (SV) and a photosensitizer protoporphyrin IX (PpIX) | TMNP under light irradiation showed huge amount of ROS production and induction in apoptotic and necrotic pathways | [73] | ||
| Temperature | Human cervical (HeLa) spheroids | Doxorubicin-loaded gold-core silica-shell nanorods with salicylic acid-loaded poly (lactic-co-glycolic acid)-based microparticles (NIMPS) | Uniform doxorubicin distribution under NIR irradiation along with spheroid surface disorganization | [74] | |
| Adenocarcinomic human alveolar basal epithelial (A549) spheroids | Low temperature-sensitive liposomes (LTSLs) loaded with doxorubicin | Combination between LTSLs and mild hyperthermia induced reduction in spheroid viability | [75] | ||
| Ultrasound | Human breast cancer spheroids (MCF-7) | Microbubbles loaded with rose bengal, paclitaxel, and doxorubicin (O2MB-PTX-Dox/O2MB-PTX-RB) | MCF-7 spheroid volume reduction and increase in necrotic cells under sonodynamic exposure of O2MB-PTX-Dox/O2MB-PTX-RB | [80] | |
| Human pancreatic (BxPC-3) spheroids | Gemcitabine-modified phospholipid incorporated into a single microbubble formulation loaded with PTX (Lipid-Gem-PTX MB) | A statistically significant reduction in BxPC-3 spheroid volume was observed when spheroids underwent to US exposure of Lipid-Gem-PTX MB | [82] | ||
| Magnetic | On-chip system | Magnetic NPs (MNPs) | Particles with a diameter size between 10 and 100 μm displayed the similar trend | [85] | |
| Microfluidic chip | Magnetic NPs (MNPs) | MNPs showed highly spherical shape and superparamagnetic properties in the system | [86] |