Cell permeable nanoconjugates of shell-crosslinked knedel (SCK) and peptide nucleic acids (“PNAs”) with uniquely expressed or over-expressed mRNA targeting sequences for early diagnosis and therapy of cancer
A functional biologically active particle conjugate useful for diagnosis and treating cancer as a bioportal comprises a nanoscale particle having associated therewith an intracellular targeting ligand comprising a PNA, or another nuclease resistant oligonucleotide analog such as MOE-mRNA (2′-methoxyethyl mRNA) or LNA (locked nucleic acid), having a sequence that binds selectively to an uniquely expressed or overexpressed mRNA specific to the cancer or disease state in a living mammal. In one aspect the uniquely overexpressed target specific to the cancer or disease state is the unr mRNA which can be targeted by the antisense sequence PNA50.
1. A diagnostic target-specific imaging probe comprising an intracellular targeting ligand comprising a peptide nucleic acid, wherein the peptide nucleic acid is SEQ ID NO: 3, or a nuclease resistant oligonucleotide analog, wherein the nuclease resistant oligonucleotide analog is a MOE-mRNA of SEQ ID NO: 3 or a LNA of SEQ ID NO: 3, wherein the SEQ ID NO: 3 binds selectively to an uniquely expressed or overexpressed mRNA, wherein the uniquely expressed or overexpressed mRNA is an unr mRNA, a permeation peptide, and at least one detectably labeled compound.
2. A pharmaceutical kit comprising the diagnostic target-specific imaging probe of claim 1 and a pharmaceutically acceptable carrier, excipient, diluent, or saline composition.
3. The diagnostic target-specific imaging probe of claim 1 , wherein the permeation peptide is selected from the group consisting of a HIV-1 TAT protein transduction domain, KPKKKRKV, GRKKRR, and four lysine residues.
4. The diagnostic target-specific imaging probe of claim 1 , wherein the at least one detectably labeled compound is selected from the group consisting of a fluorophore, a radionucleotide, and combinations thereof.
5. A diagnostic target-specific imaging probe comprising an intracellular targeting ligand comprising a permeation peptide, a peptide nucleic acid, wherein the peptide nucleic acid is SEQ ID NO: 3, and at least one detectably labeled compound.
6. The diagnostic target-specific imaging probe of claim 5 , wherein the permeation peptide is selected from the group consisting of a HIV-1 TAT protein transduction domain, KPKKKRKV, GRKKRR, and four lysine residues.
7. The diagnostic target-specific imaging probe in accordance with claim 5 , further comprising a shell crosslinked knedel shell crosslinked nanoparticle.
8. The diagnostic target-specific imaging probe in accordance with claim 1 , further comprising a shell crosslinked knedel shell crosslinked nanoparticle.