Table 4.

In vitro Antitumor Efficacy and Mechanisms of St-Mc-DDS

St Type	St-Mc-DDS	Drugs	Cell Line	Cellular Uptake	Subcellular Localization	MMP (Δψm)	Cytotoxicity (IC50)	Apoptosis Promotion	Ref.
pH	Polymer-drug conjugates	DOX	4T1	Endocytosis pathway	Lysosome & mitochondria	1.9-fold higher	2.5-fold lower	Yes (Cas-3 activation)	[81]
	Eph A10/TPP-DTX liposomes	Docetaxel	MCF-7	EphA 10 receptor mediated cell endocytosis	Mitochondria	0.14-fold lower	Lower IC50 value	Yes (highest Cas-3 and Cas-9 expression)	[42]
	CTPP-CSOSA/celastrol micelles	Celastrol	MCF-7	Endocytosis pathway	Mitochondria	Dropped dramatically	Lower IC50 value	Yes (obvious increase in Cas-3 and Cas-9 activity)	[43]
	HER-2/DOX DQAsomes	DOX	MCF-7 and MCF-7/ADR	HER-2 peptide-mediated endocytosis	Mitochondria	A 6.9% decrease	2.6-fold lower	Yes (activated Cas-3 and Cas-9)	[36]
	PEG-AIE-TPP micelle	AIE-TPP	MCF-7	Endocytosis pathway	Mitochondria	–	–	Yes	[44]
	HPMA-MSN/DTX nanoparticles	Docetaxel	HeLa	Endocytosis pathway	Mitochondria	Collapse	A lower IC50 compared to pH7.4	Yes	[45]
	TPP-Que-PEG nanoparticles	Quercetin	HeLa	Endocytosis pathway	Mitochondria	Markedly decrease	–	Yes (improved activity of Cas-9 and Cas-3)	[46]
	DSPE-KLA-DMA/PTX liposomes	Paclitaxel	A549	Macropinocytosis and clathrindependent endocytosis	Mitochondria	Reduce the most	20-fold lower	Yes (activated Cas-9 and −3)	[47]
	PDPA/TPGS/DOX micelles	DOX	MCF-7/ADR	Endocytosis pathway	Mitochondria	Reduced by 80%	23-fold lower	Yes	[48]
	HHG2C18 liposomes	Temsirolimus (CCI-779)	A498	Endocytosis pathway	Mitochondria	–	–	–	[49]
	CAT@S/Ce6-CTPP/DPEG	Catalase	4T1	Endocytosis pathway	Mitochondria	–	–	Yes	[20]
Redox	Glucose-PEG-peptide-TPP-PAMAM-PTX conjugates	Paclitaxel	MCF-7/ADR	Transporter-mediated pathways	Mitochondria	Destruction	Strongest cytotoxicity	–	[78]
	TPP-oHA-S-S-Cur micelles	Curcumin	MDA-MB-231	CD44-mediated endocytosis	Mitochondria	–	Better cellular cytotoxicity	–	[50]
	PLGA/C18-PEG-TPP/DLPE-S-S-mPEG/PTX nanoparticles	Paclitaxel	MCF-7	Macropinocytosis	Mitochondria	Decrease	Higher cytotoxicity	Yes (activated Cas-9 and −3)	[51]
	TPP-PPA micelles	PPA	4T1	–	Mitochondria	Reduction	Good cytotoxicity	Yes (activated Cas-9 and −3)	[76]
Enzyme	HA/PEG/berberine derivative nanodrugs	Berberine derivative	A549	CD44-mediated endocytosis	Mitochondria	The most significant decrease	A much lower IC50	Yes (highest activities of Cas-9 and −3)	[19]
	Non-isocyanate polyurethane-TPP/DOX nanocapsule	DOX	LN229	–	Mitochondria	–	–	–	[52]
	TPP-peptide nanoassemblies	TPP-peptide	Saos2	Caveolae/lipid-raft mediated endocytosis	Mitochondria	–	Higher cytotoxicity	Yes	[53]
Light	Perfluorooctyl bromide/IR780 liposomes	IR780	4T1	Cell endocytosis	Mitochondria	–	Higher cytotoxicity	–	[54]
	Iridium/Fe3O4 nanozyme	Iridium	Hela	–	Mitochondria	Decreased markedly	Higher cytotoxicity	Yes	[55]
	IR-780/DSPE-PEG2K-TPP liposomes	IR-780; Lonidamine	LL/2	Cell endocytosis	Mitochondria	Decrease	Higher cytotoxicity	Yes	[56]
	AuNS-KLA-TPP/HA/DOX nanoparticles	DOX	SCC-7	CD44 receptor mediated endocytosis pathway	Mitochondria	Decrease	Higher cytotoxicity	Yes	[58]
	TPP/Ce6/PEG-/FA-PEG-Pt@Au nanoparticles	Ce6	MCF-7	Clathrin-mediated endocytosis pathway	Mitochondria	Loss	Higher cytotoxicity	Yes (activated Cas-3)	[59]
	PPa-NGO-mAb nanodrug	PPa	U87-MG	Integrin αvβ3 receptor mediated endocytosis	Mitochondria	–	Higher cytotoxicity	Yes	[64]
	Yb/Tm/TiO2 nanoparticles	Yb/Tm/TiO2	Hela	–	Mitochondria	Loss	Higher cytotoxicity	Yes (activated Cas-9 and −3)	[65]
	TPP-coumarin-Fe3O4 nanoparticles	Fe3O4	Hela	–	Mitochondria	–	Hyperthermic cytotoxicity	Yes	[66]
	Cyt c aptamer-mesoporous silica-Au nanorods	Au	Hela	–	Mitochondria	–	Higher cytotoxicity	Yes	[67]
Magnetic field	DNA/PK-CP-SPION complexes	DNA	Hela	–	Mitochondria	Obviously decreased	Higher cytotoxicity	Yes	[69]