Table 2.

Active targeting of CSCs based on PNP

Cancer	Markers	Ligand	Polymers of nanoparticles	Agents	Results	Cell line/Model	References
Gastric cancer	CD44v6	CD44v6 antibody	PEGylated GNSs	NA	CD44v6-GNS nanoprobes actively target gastric cancer cells and inhibit tumor growth under near-infrared laser irradiation	MKN-45 and cancer xenograft mice	[40]
	CD44	HA	Pationic liposomes	Gli1	Gli1 siRNA nanoparticles can specifically block Hh signaling and significantly inhibit CSCs	AGS	[44]
	CD44	HA	PEG-PLGA	METase and 5-Fu	PEG-PLGA NPs coated with HA allow for targeted delivery of 5-Fu and METase to CSCs	NCI-N87	[41]
	CD44	HA	PAMAM	METase	The nanoparticle can disrupt mitochondrial function in CD44-positive gastric CSCs	NCI-N87	[43]
	CD44 and CD133	CD44 and CD133 antibody	PLPN	ATRA	Nanoparticle delivery to two gastric CSCs populations was achieved by diabody conjugation	NCI-N87/MKN-45	[46]
Pancreatic cancer	CD47	CD47 antibody	Iron oleate complex	Gemcitabine	The efficacy of this MMP was demonstrated against CD47-positive pancreatic cancer cells	Panc-1, BxPC-3, and PDX	[59]
	CD133	CD133 antibody	BTiO2	NA	The nanoprobe exhibited high relaxation rate, excellent photothermal efficiency, and targeting ability to pancreatic CSCs in this experiment	SW1990	[63]
	CD44	αCD44 antibody	O2LNCs	Paclitaxel	The antitumor efficacy of paclitaxel loaded with αCD44-O2 LNCs increased fourfold compared to free paclitaxel	BxPC-3	[60]
	CD44	HA	Co-poly (styrene maleic acid)	3,4-difluorobenzylidene curcumin	Nanomicelles reach tumor sites via enhanced permeability and EPR effect and reach pancreatic CSCs via CD44 receptor-mediated endocytosis	MiaPaCa-2 and AsPC-1	[61]
	CD44	HA	AgNO3 -amino acid glutamine	5-FU	Confinement of carboxymethyl inulin significantly alleviates the cytotoxicity of AgNPs and modification of HA improves targeting to CSCs	Panc-1	[62]
	CD326	Anti-human CD326	NaYF4:Yb,Er@NaGdF4	NA	Antibody-modified micelles showed good targeting	BxPc-3 and subcutaneous mouse model	[64]
Hepatic cancer	CD133	Anti-CD133 monoclonal antibody	PEI-FePt	HSV-TK suicide gene	The nanoparticle combination inhibited the growth of hepatic CSCs and induced apoptosis in vitro which was higher than any single intervention	Huh-7	[72]
	CD133	CD133 antibody	PLGA	Paclitaxel	Antibody-modified paclitaxel-loaded nanoparticles can reach target cell populations under passive and active targeting	Huh7	[71]
	CD44	CD44 antibody	Liposomal	Dox	The liposomal nanoparticles were shown to be useful for monitoring and evaluating targeting efficacy and gene therapy by noninvasive molecular imaging	HepG2	[73]
	EpCAM	Anti-EpCAM antibody	NaYF4:Yb,Er	Mitoxantrone	A smart diagnostic and therapeutic micelle based on antibody-conjugated UCNPs was prepared	BEL-7404	[74]
Colorectal cancer	CD133	CD133 antibody	PEG-PCL	SN38	Anti-CD133 antibody-conjugated SN38-loaded nanoparticles can efficiently bind to HCT116 cells	HCT116	[25]
	CD44	HA	PF33-pDNA RRPH	TRAIL	Developed a ternary multifunctional nanoparticle for in vivo gene delivery	HCT116	[82]
	CD133	RNA ligand	Amine‐functionalized dendritic mesoporous silica	Dox	A smart targeted drug delivery system based on PCAD-coated DMSNs was designed, which can control the release of Dox	HT29	[81]
	CD44v6	Fab-CD44v6	Pluronic® F127	Niclosamide	The use of targeted nanoparticles has improved the efficacy of niclosamide in colorectal CSCs	HCT116 and mouse xenograft tumor model	[84]
	CD44/CD168	HA	PEG-PLGA	PTC209	Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment	CT26-luc cells	[85]
	Prominin-1	PROM-1 targeting ligand	Apoferritin and 1-hydroxy-2,5-pyrrolidinedione	Irinotecan	Demonstrated efficacy of irinotecan as a radiosensitizer in a PROM-1-targeted NP formulation	HCT116 and mice ectopic tumor model	[86]