. 2021 Jun 15;16:4117–4146. doi: 10.2147/IJN.S315368

Table 3.

Physicochemical and Release Properties of St-Mc-DDS

St Type	Nanocarrier	Preparation	Physicochemical and Release Properties				Ref.
St Type	Nanocarrier	Preparation	Particle Size (nm)	Zeta Potential (mV)	Encapsulation Efficiency (%)	In vitro Release	Ref.
Endogenous stimuli-responsive En-St-Mc-SDDS
pH	Eph A10/TPP-DTX liposomes	Thin-flm hydration method	131.5 ± 2.6	−16.25 ± 0.38	74.7 ± 1.7	pH 5.0: ~80%	[42]
	Eph A10/TPP-DTX liposomes	Thin-flm hydration method	131.5 ± 2.6	−16.25 ± 0.38	74.7 ± 1.7	pH 7.4: ~30%	[42]
	CTPP-CSOSA/celastrol micelles	Dialysis method	63.5 ± 18.0	22.1 ± 0.3	92.3 ± 0.7	pH 5.0: ~0	[43]
						pH 7.4: ~40%
						pH 8.0: ~90%
	HER-2/DOX DQAsomes	Thin-flm hydration method	112.7 ± 3.3	12.7 ± 2.8	53.4 ± 3.8	pH 5.0: 73.5%	[36]
	HER-2/DOX DQAsomes	Thin-flm hydration method	112.7 ± 3.3	12.7 ± 2.8	53.4 ± 3.8	pH 7.4: 53.2%	[36]
	PEG-AIE-TPP micelle	Solvent evaporation method	~130.0	–	–	pH 5.3: ~90%	[44]
						pH 6.5: ~40%
						pH 7.4: ~30%
	HPMA-MSN/DTX nanoparticles	Stirring-centrifugation method	190.4 ± 4.9	−18.2	8.34 (LC)	pH 5.0: 4.2 mV (1 h)	[45]
						pH 6.5: 4.2 mV (2 h)
						pH 7.4: −16.4 mV
	PEG-TPP-Que nanoparticles	Dialysis method	93.5 ± 0.1	23.6 ± 1.5	–	–	[46]
	DSPE-KLA-DMA/PTX liposomes	Thin-film hydration method	155.3 ± 2.2	~-15.0	81.8 ± 0.7	pH 4.5: 35.0 mV	[47]
						pH 5.5: 25.0 mV
						pH 6.8: 10.0 mV
						pH 7.4: ~-15.0 mV
	PDPA/TPGS/DOX micelles	Thin-film hydration method	57.3 ± 3.4	–	~70	pH 5.5: ~70%	[48]
	PDPA/TPGS/DOX micelles	Thin-film hydration method	57.3 ± 3.4	–	~70	pH 7.4: ~35%	[48]
	HHG2C₁₈ liposomes	Film dispersion method	–	−22.9	96.75 (Temsirolimus) 93.76 (Coumarin 6)	pH 4.5: 25.5 mV	[49]
						pH 5.5: 15.3 mV
						pH 6.5: 6.3 mV
						pH 7.4: −22.9 mV
Redox	TPP-oHA-S-S-Cur micelles	Dialysis method	122.4 ± 23.4	−26.55 ± 4.99	–	0 µM GSH: 32.5%	[50]
						10 µM GSH: 37%
						2 mM GSH: 57.5%
						10 mM GSH: 75.3%
	PLGA/C18-PEG-TPP/DLPE-S-S-mPEG/PTX nanoparticles	Singlestep nanoprecipitation strategy	178.6 ± 1.2	2.4 ± 0.8	8.3 ± 0.1 (LC)	10 µM GSH: 2.4 mV	[51]
	PLGA/C18-PEG-TPP/DLPE-S-S-mPEG/PTX nanoparticles	Singlestep nanoprecipitation strategy	178.6 ± 1.2	2.4 ± 0.8	8.3 ± 0.1 (LC)	10 mM GSH: 17.2 mV	[51]
Enzyme	HA/PEG/berberine derivative nanodrugs	nano-precipitation method	151.2 ± 2.7	−25.8 ± 1.4	70.1 ± 2.3	HAase/pH 4.5: 13.47 mV	[19]
						HAase/pH 5.6: 10.39 mV
						HAase/pH 7.4: slightly negative potential
	Non-isocyanate polyurethane-TPP/DOX nanocapsule	Inverse miniemulsion process	250~260	–	91~94	Esterase: 93-fold higher at emission intensity	[52]
	TPP-peptide nanoassemblies	Self-assembly method	L-₁P: 121	–	–	ALP: 635 nm (L-₁P)	[53]
			L-₁P: 121			ALP: 196 nm (D-₁P)
			D-₁P: 58			ALP: 196 nm (D-₁P)
	Peptide/DNA complexes	Self-assembly method	130~480	−3~-35	–	–	[37]
Exogenous stimuli-responsive Ex-St-Mc-SDDS
Light	Perfluorooctyl bromide/IR780 liposomes	One-step emulsion strategy	268.3	–	92.5	Laser exposure: keep 56% of the largest absorbance when IR780 is photobleached	[54]
	Iridium/Fe₃O₄ nanozyme	Magnet precipitated and separated method	~8	–	–	Temperature increment due to laser and iridium	[55]
	IR-780/DSPE-PEG2K-TPP liposomes	Film-hydration and sonication method	125.0 ± 63.4	23.5 ± 3.1	83.6	37 °C: 34.1%	[56]
						43 °C: 74.9%
						NIR: 78.2%
	mPEG-CHO-PAIE-TPP nanoparticles	Synthetic method	~200	2.96 ± 0.2	–	pH 5.4: hydrolysis	[57]
						pH 6.8: hydrolysis
						pH 7.4: mPEG-CHO is undetectable
	AuNS-KLA-TPP/HA/DOX nanoparticles	Stirring-centrifugation method	94.6	−13.1	–	pH 6.8 + HAase + NIR: 75%	[58]
	TPP/Ce6/PEG-/FA-PEG-Pt@Au nanoparticles	Ultrasound-stirring-centrifugation method	21.5	−42	–	–	[59]
	Au-dcHSA-PEO-TAT-TPP nanoparticles	Synthetic method	85.2	10.67	–	Stable in phosphate buffer, glucose, NaCl, pH 3.9, pH 10 and protease/trypsin solutions	[60]
	PPa-NGO-mAb nanodrug	Synthetic method	100~400	–	–	Stable in water, PBS, DMEM, serum and different pH solutions	[64]
	Yb/Tm/TiO2 nanoparticles	Thermal decomposition reaction	~100	–	–	–	[65]
	TPP-coumarin-Fe₃O₄ nanoparticles	Synthetic method	~15	–	–	–	[66]
	Cyt c aptamer-mesoporous silica-Au nanorods	Synthetic method	~20	–	7.3 (LC)	NIR (no): 5%	[67]
						NIR (first time): 17%
						NIR (second time): 7%
	SWNT-PEG nanotubes	Synthetic method	–	–	–	–	[68]
Magnetic field	DNA/PK-CP-SPION complexes	Grignard reagent reaction method	49.7	32.7	–	–	[69,79]
	Fe₃O₄@mSiO₂-TPP/CDs nanoparticles	Liquid-solid-solid synthetic route	82.30	16.33	–	–	[70]
	AMB-1-Cyt c aptamer bacterial magnetic nanoparticles	Originating from Magnetospirillum sp. AMB-1	50	–	–	–	[71,80]
Multi-responsive St-Mc-SDDS
pH/light	Catalase@SiO₂/Ce6-CTPP/DPEG nanoparticles	Synthetic method	~100	−18	–	Protease K: 70% (remained activity)	[20]
	Fe₃O₄@DMSA/DOX nanoparticles	Synthetic method	102.02 ± 0.6	–	>90	pH 5.0: 80.3%	[72]
						pH 7.4: 19.2%
						pH 5.0+NIR: 98.5%
						pH 7.4+NIR: 30.0%
Redox/light/magnetic field	DOX/Fe₃O₄/TPP-PDA-s-s-mPEG nanoparticles	Synthetic method	165	4	41 (LC)	pH 7.4+ GSH: 18 mV	[73]
						pH 5.0: ~35%
						pH 7.4: ~15%
						pH 5.0+NIR: ~65%
						pH 7.4+NIR: ~40%
Magnetic field/light	Fe₃O₄@PDA@mSiO₂-TPP/-PEG nanoparticles	Synthetic method	275	−5.2	–	–	[74]
pH/redox/temperature	MBA-PDA-PEG-PNiPMA/Pc 4 nanogel	Synthetic method	108.1 ± 11.1	−5.62 ± 1.40	–	pH 7.4: 108 nm, 13.6%	[75]
						pH 5.0: 360 nm, 30.3%
						DTT/EDTA: 1200 nm
						Temperature>39 °C: particle size: increase
Redox/light	TPP-PPA micelles	Modified oil-in-water emulsion-based self-assembly method	176.3 ± 12.3	–	3.1 ± 0.2 (LC)	Low ROS: 30 μg/cm²	[76]
Redox/light	TPP-PPA micelles	Modified oil-in-water emulsion-based self-assembly method	176.3 ± 12.3	–	3.1 ± 0.2 (LC)	High ROS: 50 μg/cm²	[76]
Redox/enzyme	Glucose-PEG-peptide-TPP-PAMAM-PTX conjugates	Synthetic method	42.5 ± 18.4	2.9 ± 1.1	–	0 µM GSH: 26%	[78]
						10 µM GSH: 52%
						10 mM GSH: 79%

Notes: The bold texts refer to the Mc-targeting components in St-Mc-DDSs. These components include an Mc group or an Mc molecule (lipophilic cation, peptide or aptamer), and a material. Abbreviation: LC, loading capacity.