Table 2. Reviewed stimuli employed for drug delivery using MSNs.

Stimuli	Mechanims	Ref.
Internal stimuli
pH	Acidic cleavage (chemical)	[48, 112, 113]
	Host-guest interaction	[114, 115]
	Endosomal and lysosomal acidic pH	[116, 118]
	Self immolative polymers	[117]
Redox	S-S cleavage disassembly	[119, 121]
	S-S cleavage unfolding	[122]
	Redox induced solubility shift	[123]
Enzymes	Peptide sequence cleavage	[54, 124]
	Prodrug conversion	[125]
Small molecules	Glucose concentration	[126, 127]
	Glucose-mediated response to H2O2	[128]
	Generation of additional ROS species via Fenton reaction or α-tocopheryl	[132, 133]
	H2O2 rich microenvironment	[134]
	H2O2 or NO concentration	[135]
	Competitive binding or displacement reactions in the presence of ATP	[140, 141]
External stimuli
Light	UV-vis	[45, 146, 147, 148, 149]
	NIR	[151]
	NIR to thermal conversion: photothermia	[153]
	conversion of NIR light to UV-vis light: upconversion	[152, 154, 155, 156, 157, 158, 159, 160, 161, 162]
Temperature	Conformational changes in polymers:
	pNIPAM and analogs	[163, 164, 165, 166]
	PEG acrylates	[167]
	Disassembly of coiled coil motifs	[168]
Magnetic fields	Increase of temperature under the action of an alternating magnetic field
	Superparamagnetic cores in core@MSNs: Fe3O4 and Fe3O4/Fe cores	[169, 170]
	IONPs in the silica network	[171, 172, 173]
	IONPs as mesopore caps	[174]
Ultrasounds	MSNs capping with a copolymer containing a labile acetal group which is cleaved upon US application. Change of polymer conformation due to hydrophobic to hydrophilic transformation.	[180, 181, 182]
Multi-stimuli responsive MSNs
Dual responsive MSNs	pH or ATP concentration	[184]
	pH or glucose concentration	[185, 186, 187]
	Enzyme (hyaluronidase) and redox (GSH)	[188]
Sequential release of different sized cargos	Electro-stimuli and UV irradiation	[189]
Use of dual responsive polymers	cargo loading at 4 °C and conformation change at 37 °C:
	upon US irradiation	[180]
	upon H2O2 stimulus	[190]
	dual-responsive polymers as gatekeepers:
	pH and thermoresponsive	[191]
	pH and visible light responsive	[192]
Combination of chemotherapy and PTD	Drug release under acidic pH and 1O2 generation with NIR irradiation	[193]
	1O2 generation upon 660 nm irradiation and gatekeeper cleaving by the generated 1O2	[194]
Three gated MSNs	Redox, enzymatic hydrolysis and contact with cell membrane	[195]

Abbreviations: ATP: Adenosine triphosphate; GSH: Glutathione; IONPs: Iron oxide nanoparticles; pNIPAM: poly(N-isopropylacrylamide); NIR: Near Infrared radiation; PEG: poly(ethyleneglycol); PDT: Photodynamic theraphy; ROS: Reactive Oxigen Species; UV-vis: Ultraviolet-Visible radiation.