Chemical modification of ligands for cell receptors to introduce foreign compounds into the cells.
OBJECTIVE
In all forms of drug therapy, clinicians must ensure that the maximum therapeutic benefit is achieved without inducing unacceptable toxicity. An improvement in the therapeutic index could be achieved through the targeting of drugs selectively to cancer cells.


METHODS
We have developed a delivery system that uses receptor-mediated endocytosis to introduce oligodeoxynucleotides into cells bearing receptors for the ligands used as a vehicle. Human transferrin, as well as folic acid and steroid, has been covalently linked to polylysines of various sizes through a disulfite bridge and used as oligomer carriers.


CONCLUSIONS
The inhibitory effect of c-myb antisense oligodeoxynucleotides conjugate to modified transferrin on LoVo Dx cell proliferation was examined. Protocols to modify physiologic ligands to be used as vehicles for a selective delivery are shown. Modified ligand molecules should also be used to covalently bind liposome-carrying compounds able to affect neoplastic growth.
Citro
G
G
Laboratorio Chemioterapia Sperimentale Preclinica, Istituto Regina Elena, Rome, Italy.
Ginobbi
P
P
Candiloro
A
A
Meloni
A
A
Sarti
P
P
Milani A [corrected to Meloni
A ]
A]
D002478:Cells, Cultured; D004247:DNA; D004268:DNA-Binding Proteins; D004337:Drug Carriers; D004705:Endocytosis; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008081:Liposomes; D009711:Nucleotides; D011107:Polylysine; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger / Q000032:analysis; D011955:Receptors, Drug; D014168:Transferrin
D004268:DNA-Binding Proteins; D004337:Drug Carriers; D008081:Liposomes; D009711:Nucleotides; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D011955:Receptors, Drug; D014168:Transferrin; D011107:Polylysine; D004247:DNA; D016650:Fluorescein-5-isothiocyanate