Dendrimer conjugates
The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.
1. A dendrimer conjugate comprising a linker,
wherein said linker is selected from the group consisting of an elimination linker, a cyclization linker, a glucoronidase sensitive linker, a branched self-elimination linker, a heteroaromatic nitrogen containing compound linker, and a hypoxia induced linker,
wherein said linker is conjugated to a G5 PAMAM dendrimer and at least one ligand selected from the group consisting of a therapeutic agent, an imaging agent, and a targeting agent.
2. The dendrimer conjugate of claim 1 , wherein said G5 PAMAM dendrimer is conjugated to at least one ligand selected from the group consisting of a therapeutic agent, an imaging agent, and a targeting agent.
3. The dendrimer conjugate of claim 1 , wherein said elimination linker is a 1,4 elimination linker.
4. The dendrimer conjugate of claim 1 , wherein said elimination linker is a 1,6 elimination linker.
5. The dendrimer conjugate of claim 1 , wherein said hypoxia induced linker is esterase sensitive.
6. The dendrimer of claim 1 , wherein said hypoxia induced linker is indolequinone.
7. The dendrimer conjugate of claim 1 , wherein said therapeutic agent is Naloxone.
8. The dendrimer of claim 1 , wherein said imaging agent is selected from the group consisting of a radioactive label, fluorescein isothiocyanate (FITC), 6-TAMARA, acridine orange, and cis-parinaric acid.
9. The dendrimer of claim 1 , wherein said targeting agent is selected from the group consisting of an agent binding a receptor selected from the group consisting of CFTR, EGFR, estrogen receptor, FGR2, folate receptor, IL-2 receptor, and VEGFR; an antibody that binds to a polypeptide selected from the group consisting of p53, Mucl, a mutated version of p53 that is present in breast cancer, HER-2, T and Tn haptens in glycoproteins of human breast carcinoma, and MSA breast carcinoma glycoprotein; an antibody selected from the group consisting of human carcinoma antigen, TP1 and TP3 antigens from osteocarcinoma cells, Thomsen-Friedenreich (TF) antigen from adenocarcinoma cells, KC-4 antigen from human prostrate adenocarcinoma, human colorectal cancer antigen, CA125 antigen from cystadenocarcinoma, DF3 antigen from human breast carcinoma, and p97 antigen of human melanoma, carcinoma or orosomucoid-related antigen; transferrin; and a synthetic tetanus toxin fragment.
10. The dendrimer of claim 1 , wherein said therapeutic agent is selected from the group consisting of a chemotherapeutic agent, an anti-oncogenic agent, an anti-angiogenic agent, a tumor suppressor agent, an anti-microbial agent, an expression construct comprising a nucleic acid encoding a therapeutic protein, a pain relief agent, a pain relief agent antagonist, an agent designed to treat arthritis, an agent designed to treat inflammatory bowel disease, an agent designed to treat an autoimmune disease, and an agent designed to treat inflammatory pelvic disease.