Table 1.

Some physical and bioactivity characteristics of sequential-targeting drug delivery systems.

NP Matrix	Drug	Targeting Moieties	Cellular Targeting	Subtargeting Moieties	Target Organelles	References
liposomes	DOX	transferrin	transferrin receptors	octaarginine	nucleus	[21]
silica	DOX	galactose	galactose ligands	TAT peptides		[22]
silica	DOX DEX	folic acid	folate receptors	DEX-GR complex		[23]
peptide	HCPT and cisplatin	RGD peptide moiety	integrin	positive charge		[24]
aptamer	gemcitabine	AS1411	nucleolin	AS1411		[25]
aptamer	DOX	APTA12	nucleolin	APTA12		[26]
carbon	DOX	positive charge	phosphate	negative charge		[27,28]
polymer	apoptin	positive charge	negative charge	HKRRR		[29]
polymer	GNA002	cRGD	Integrin ανβ3-receptor	hexa-arginine		[30]
peptide	siRNA and NLS with influenza virus hemagglutinin	AS1411	nucleolin	NLS peptide		[31,32]
peptide	camptothecin	HNLS-3	negative charge	HNLS-3		[33]
polymer	9-nitro-20(S)-camptothecin	HA	CD44 receptor	TAT peptides		[34]
silica	DOX	HA	CD44 receptor	TPP	mitochondria	[35]
silica	DOX	HA	CD44 receptor	TPP		[36]
lipid	paclitaxel	HA	CD44 receptor	DQA		[37]
graphene oxide	DOX	GA	GA receptor	GA		[38]
gelatin	DOX	GA	GA receptor	GA		[39]
polysaccharide	SS-31 peptides	HA	CD44 receptor	SS-31 peptides		[40]
nanodiamonds	DOX	folic acid	folate receptor	MLS peptides		[41]
polymer	siBcl-xL	HA	CD44 receptor	KLA		[42]
silica	5-fluorouracil	HA	CD44 receptor	coumarin		[43]
lipid	cyclopeptide RA-XII	HA	CD44 receptor	TPP		[44]
metal	DOX	folic acid	folate receptor	TPP		[45]
polymer	DOX	folic acid	folate receptor	TPP		[46]
lipid/polymer hybrid nanovehicles (lpnvs)	N/A	penetratin	electrostatic interaction between the LPNV and cells	penetratin	endoplasmic reticulum	[47]
polymer	Ru-1	biotin	biotin receptor	tetraphenylporphyrin		[48]
lipid	DOX + retinoic acid	chondroitin sulfate	CD44 receptor	chondroitin sulfate	Golgi apparatus	[49,50]

DOX: doxorubicin; PTX: Paclitaxel; DEX: dexamethasone; HCPT: 10-hydroxycamptothecine; RGD: Arg-Gly-Asp; HA: hyaluronic acid; GA: glycyrrhetinic acid; TPP: triphenylphosphine; DQA: dequalinium; DEX-GR complex: dexamethasone-glucocorticoid receptor; APTA12: gemcitabine incorporated G-quadruplex aptamer; NLS: nuclear localization signal; HNLS-3: PFVYLIPKKKRKVHHHHHHGC-NH₂; MLS: mitochondrial localizing sequence; siBcl-xL: small interfering RNA (siRNA) against Bcl-xL.