Table 2.

Summary of different stimuli-responsive nanocarriers.

Stimuli Type	Advantages	Challenges/Limitations	References
Thermo-Responsive	Tunable drug release	The clearance and accumulation of NPs in off-target organs such as the liver and spleen Limited to the targets with known localization	[80,83,84]
pH-Sensitive	Localized delivery Reduced side-effects Prolonged activity	Fast clearance Specificity limited to the microenvironment	[80,86,87,88,90,91,92,93,94,95]
Ultrasound-Triggered	On-demand drug release Enhanced drug accumulation Non-invasive	Production of intracellular free radicals in response to ultrasound Limited to the targets with known localization	[80,96,97,98]
Light-Responsive	Little to no leakage in the absence of a trigger High efficiency in drug releasing	Non-sustained drug release, might require multiple administration Side-effects of byproducts DNA damage by UV light Limited to the targets with known localization	[99,100,101]
Redox-Responsive	Localized delivery Prompt response in cargo release	Quickly oxidized Fast clearance Specificity limited to the microenvironment	[103,105,106]
Magnetic-Targeting	Improved targeting efficiency	Energy consuming Selection of the proper magnetic carrier and magnetic force Low therapeutic efficacy Difficult to control magnetic nanoparticle distribution and deep tissue penetration Limited to the targets with known localization	[122,123,124,125,126]
Enzyme-Responsive	Localized delivery Higher therapeutic efficacy	Less controllable drug release Difficulty in constructing enzyme-specific substrate	[127,128,129,130,131,133]