Table 5 Characteristics of Stimuli-Responsive Nanoparticles
From: Developments in nanotechnology approaches for the treatment of solid tumors
Stimulus | Mechanism | Advantages | Limitations | Example |
|---|---|---|---|---|
pH and enzyme-sensitive (endogenous) | Acidic TME, MMPs, and intracellular GSH trigger cleavage of sensitive linkers, enabling controlled drug release | Enhances site-specific activation, drug retention, and deep tumor penetration; reduces systemic toxicity | Enzyme levels and acidic pH can also be present in non-cancerous inflamed or infected tissues, risking off-target activation | Dual-sensitive Dendrimer-Dextran nanoparticles with MMP/pH-cleavable linker in GBM [266] |
Redox (endogenous) | Tumor Hâ‚‚Oâ‚‚ activates FePt-mediated Fenton reaction, generating ROS and inducing oxidative stress | Enhances chemo- and radiosensitization via ROS-induced apoptosis and DNA damage | Effectiveness may be reduced by tumor antioxidant defenses (e.g., catalases) | Cysteine-coated FePt NPs with cisplatin/radiotherapy in NSCLC [190] |
Light -PTT/PDT (exogenous) | NIR or visible light triggers heat generation (PTT) or ROS production (PDT) by photothermal agents or photosensitizers | Enables precise, non-invasive, on-demand tumor ablation; can induce immune activation | Limited penetration depth (PTT); efficacy depends on oxygen presence (PDT); risk of collateral damage to surrounding tissues | PDT: AuNP–antibody conjugates for CSC-targeted lung cancer therapy [231] PTT: Acid-functionalized MWCNTs eradicate breast tumors and promote immune cell infiltration [235] |
Magnetic field (exogenous) | Alternating magnetic field induces localized heating of SPIONs (magnetothermal effect), also triggering drug release | Enables deep, non-invasive control of release; potential for combined hyperthermia and ROS-mediated therapy | Requires external magnetic setup; heat dissipation must be tightly controlled | FA-functionalized Fe₃O₄ SPIONs with DOX achieve targeted chemo-hyperthermia in MCF-7 cells [267] |
Ultrasound (exogenous) | High-intensity focused ultrasound (HIFU) induces thermal ablation and cavitation | Enables deep tissue penetration, non-invasive ablation, and enhanced drug delivery; permits the use of sonodynamic agents (e.g., hematoporphyrin monomethyl ether, HMME) which produce ROS upon ultrasound exposure | Limited by tissue barriers (bone/gas), energy dispersion, and potential off-target heating | PFP/HMME-loaded PLGA nanoparticles enhance HIFU ablation via cavitation and sonodynamic synergy in breast cancer models [268] |