Table 2

Conjugates of therapeutic agents with Tf

Therapeutics	Linker Strategy	Biological Evaluation	Special Remarks	References
Doxorubicin	Phenylacetyl hydrazone	MDA-MB-435	Slightly improved activity and significantly reduced toxicity	Kratz et al., 2000
	Maleimide spacer	MDA-MB-468 and LXFL 592; L292	Amide or acid-sensitive link	Kratz et al., 1998a
	Glutaraldehyde	K562	Mechanistic studies	Lai et al., 1998
		HeLa		Bërczi et al., 1993a
		K562		Sun et al., 1992
		K562		Barabas et al., 1992
		H-Meso, HL60, Hep2	Plasma membrane as the target	Barabas et al., 1991
		NuGC4, SW403, tumor-bearing mice	More potent against resistant cell lines	Singh et al., 1998
		KB-3-1, KB-8-5, KB-C1, KB-V1, MCF-7	Prolong lifespan of the mice effectively against multidrug-resistant tumor cells	Fritzer et al., 1996
		Resistant K562	Conjugation to Ga₂-Tf	Wang et al., 2000
		K562, HL60	Dose-dependent inhibition	Hatano et al., 1993
		K562, HL60	Inhibition of both cells	Bërczi et al., 1993b
		K562	Enhanced cytotoxicity	Fritzer et al., 1992
		Patients	Enhanced cytotoxicity	Sizensky et al., 1992
	PHPMA	P388	Conjugates kill the leukemia cell	Faulk et al., 1990
	Liposome-PEG	C6 glioma	Polymer conjugated, Tf-targeted	Št'astný et al., 1999
			Encapsulated in Tf-liposome-PEG	Eavarone et al., 2000
Toxin CRM107	Thioether bond	scU87Mg, tumor-bearing mice	Effective in vitro but ineffective in vivo	Engebraaten et al., 2002
		Rat-bearing U251MG	Chloroquine block the toxicity	Hagihara et al., 2000
		Patients	Interstitial microinfusion	Laske et al., 1997
		K562 and SNB75	Cytosol translocation	Johnson et al., 1988
MMC	Glutaric anhydride spacer	HepG2 and cultured rat hepatocyte	Inhibited the growth of the HepG2 cell	Tanska et al., 2001
		HL60	TfR-mediated internalization	Tanska et al., 1998
		Sarcoma 180		Tanska et al., 1996
Daunorubicin	Glutaraldehyde	NCI-H69 (SCCL)	10 times effective over free drug	Bejaoui et al., 1991
Insulin	Disulfide	Caco-2 and diabetic rat	A slow but prolonged hypoglycemic effect and dose-dependent	Xia et al., 2000
Cisplatin	Tf-PEG-liposome	MKN45P, tumor bearing mice	Increase drug level in tumor cells and higher animal survival rates	Iinuma et al., 2002
Chlorambucil	Maleimide spacer	MCF7, MOLT4	Ester or acid-sensitive link, inhibit growth of tumor cells	Beyer et al., 1998
F(ab′)₂	Maleimide spacer	K562	Acid-labile conjugates	Wellhöner et al., 1991
Ricin A	Disulfide	In vitro	Intracellular pathway	Kornfeld et al., 1991
α-IFN	Liposome-PLL	MBT2	Tf-PLL promotes delivery and enhances antiproliferative activity	Liao et al., 1998

α-IFN, α-interferon; F(ab′)₂, anti-tetanus fragments; MMC, mitomycin C.