Doxorubicin Containing Nanoplexes and Uses Thereof
AssigneeUniversity of Baltimore, Maryland
InventorMixson Archibald James
Life of this patent
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Abstract
The present invention provides tumor-targeting nanoplexes. Generally, a tumor-targeting nanoplex is a chemotherapeutic agent DNA conjugate with a first tumor-targeting agent and an optional second tumor-targeting agent linked thereto, such as a doxorubicin plasmid DNA conjugate and a linear histidine-lysine peptide with an optional cRGD-PEG-H3K4b second targeting agent. Also provided are methods for treating a cancer in a subject and for decreasing growth of a tumor in a cancer in a subject in need thereof in which the tumor targeting nanoplex is administered.
Claims27
1:
- A tumor-targeting nanoplex, comprising:
- a chemotherapeutic agent DNA conjugate comprising a chemotherapeutic agent intercalated to a plasmid DNA;
- and
- a first tumor-targeting agent ionically linked to the chemotherapeutic agent DNA conjugate.
2:
- The tumor-targeting nanoplex of claim 1, further comprising a second tumor-targeting agent conjugated to the tumor targeting nanoplex to enhance targeting thereof.
3:
- The tumor-targeting nanoplex of claim 3, wherein the second tumor-targeting agent is cRGD-PEG-H3K4b, RGD-PEG-H3K4b, NGR-PEG-H3K4b, or CGKRK-PEG-H3K4b.
4:
- The tumor-targeting nanoplex of claim 1, wherein the first tumor-targeting agent is a linear histidine-lysine peptide sequence or a branched histidine-lysine peptide each comprising at least one —KHHK— peptide sequence.
5:
- The tumor-targeting nanoplex of claim 1, wherein the tumor-targeting agent is a delivery agent.
6:
- The tumor-targeting nanoplex of claim 1, wherein the chemotherapeutic agent is doxorubicin, epirubicin, daunorubicin, or mitoxantrone.
7:
- The tumor-targeting nanoplex of claim 1, wherein the chemotherapeutic agent and the plasmid DNA are in a wt/wt ratio of 1:2, 1:4, 1:8, 1:16, or 1:32.
8:
- The tumor-targeting nanoplex of claim 7, wherein the chemotherapeutic agent and the plasmid DNA are in a ratio of 1:8 wt/wt.
9:
- The tumor-targeting nanoplex of claim 7, wherein the chemotherapeutic agent and the plasmid DNA are in a ratio of 1:16 wt/wt.
10:
- The tumor-targeting nanoplex of claim 1, wherein the first tumor targeting agent and the plasmid DNA are in a wt/wt ratio of 1:2, 1:4, 1:6, or 1:8.
11:
- The tumor-targeting nanoplex of claim 10, wherein the first tumor targeting agent and the plasmid DNA are in a ratio of 1:2 wt/wt.
12:
- The tumor-targeting nanoplex of claim 1, wherein the nanoplex has a size of about 50 nm to about 250 nm.
13:
- A method for treating a cancer in a subject, comprising administering to the subject a nanoplex comprising a chemotherapeutic agent DNA conjugate comprising a chemotherapeutic agent intercalated with a plasmid DNA and a first tumor-targeting agent ionically linked to the chemotherapeutic agent DNA conjugate.
14:
- The method of claim 13, wherein the nanoplex further comprises a second tumor-targeting agent conjugated to the tumor-targeting nanoplex to enhance targeting thereof.
15:
- The method of claim 14, wherein the second tumor-targeting agent is cRGD-PEG-H3K4b, RGD-PEG-H3K4b, NGR-PEG-H3K4b, or CGKRK-PEG-H3K4b.
16:
- The method of claim 13, wherein the first tumor-targeting agent is a linear histidine-lysine peptide or a branched histidine-lysine peptide with at least one KHHK peptide sequence.
17:
- The method of claim 13, wherein the first tumor-targeting agent is a delivery agent.
18:
- The method of claim 13, wherein the cancer is a breast cancer, an ovarian cancer, a melanoma, a colon cancer, a pancreatic cancer, a brain cancer, a bladder cancer, a lung cancer, or a prostate cancer.
19:
- The method of claim 13, wherein the chemotherapeutic agent is doxorubicin, epirubicin, daunorubicin or mitoxantrone.
20:
- The method of claim 13, wherein the chemotherapeutic agent is administered in a therapeutically effective amount of about 0.016 mg/Kg to about 0.2 mg/Kg.
21:
- The method of claim 13, wherein the first tumor-targeting agent and the plasmid DNA are in a wt/wt ratio of 1:2, 1:4, 1:6, or 1:8.
22:
- The method of claim 21, wherein the first tumor-targeting agent and the plasmid DNA are in a ratio of 1:2 wt/wt.
23:
- The method of claim 13, wherein the chemotherapeutic agent and the plasmid DNA are in a wt/wt ratio of 1:2, 1:4, 1:8, 1:16, or 1:32.
24:
- The method of claim 23, wherein the chemotherapeutic agent and plasmid DNA are in a ratio of 1:8 wt/wt.
25:
- The method of claim 23, wherein the chemotherapeutic agent and the plasmid DNA are in a ratio of 1:16 wt/wt.
26:
- The method of claim 1, wherein the nanoplex has a size of about 50 nm to about 250 nm.
27-45. (canceled)