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|Title:||Directed delivery of radioprotectants using a receptor specific carrier|
|Abstract:||Chemoactive radioprotectants are coupled to carrier molecules capable of binding cell receptors to form complexes that can be directed to specific non-target cells in a mixture of cells prior to radiation of the mixture so that target cells are selectively destroyed while the non-target cells are protected from radiation. Radioprotection of non-target cells is provided by using chemoactive radioprotectant complexes.|
|Inventor(s):||Enriquez; Philip (Sheldonville, MA), Jung; Chu W. (Arlington, MA), Groman; Ernest V. (Brookline, MA)|
|Assignee:||Advanced Magnetics, Inc. (Cambridge, MA)|
|Filing Date:||Apr 05, 1993|
|Claims:||1. A method of treating a mixture of cells containing target cells to be destroyed by radiation therapy and non-target cells so as to protect specific non-target cells in the mixture against damage, comprising: |
(i) selecting a radioprotectant compound;
(ii) forming a complex of the radioprotectant compound and a carrier wherein the carrier is both (i) a polysaccharide, and (ii) capable of being bound to a receptor mediated endocytosis (RME) receptor, the RME receptor being present on the non-target cells and substantially absent on the target cells; and
(iii) administering the complex to the mixture of cells.
2. A method according to claim 1, wherein the radioprotectant is a chemoactive radioprotectant compound.
3. A method according to claim 1, wherein the non-target cells of step (iii) are bone marrow cells.
4. A method according to claim 1, wherein the non-target cells of step (iii) are liver cells.
5. A method according to claim 2, wherein the radioprotectant agents are selected from the group consisting of antioxidants, enzymes, and free radical scavengers.
6. A method according to claim 1, wherein the carrier of step (ii) is selected from the group consisting of arabinogalactan, mannan, and fucoidan.
7. A method according to claim 5, wherein the carrier of step (ii) is selected from the group consisting of arabinogalactan, mannan, and fucoidan.
8. A method according to claim 5, wherein the antioxidants are sulfhydryl compounds.
9. A method according to claim 1, wherein the complex of the radioprotectant and polysaccharide carrier is capable of binding to an asialoglycoprotein receptor.
10. A method according to claim 1, wherein the complex of the radioprotectant and polysaccharide carrier is capable of binding to a mannose receptor.
11. A method according to claim 1, wherein the complex of step (ii) is a micelle comprising the polysaccharide associated with the radioprotecting compound.
12. A method of treating animal subjects having diffuse cancerous infiltrations with radiation comprising:
(i) selecting a polysaccharide carrier capable of interacting with an RME cell receptor;
(ii) modifying the carrier to form a complex with a radioprotectant agent;
(iii) administering to the subject an effective dose of the complex prior to radiation treatment so as to protect non-target cells during subsequent radiation of tissues at doses sufficient to destroy malignant cells.
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