Nanoparticle formulations
This present disclosure relates to methods and compositions comprising biologically active nanoparticle formulations of MYC protein. Provided are methods of making the nanoparticle formulations and methods of using the nanoparticle formulations for treatment.
1. A composition comprising a population of biologically active nanoparticles comprising one or more MYC-containing polypeptides wherein:
a) the average diameter of the biologically active nanoparticles is between about 80 nm and about 150 nm;
b) the pH of the formulation is at least about pH 6.0, and no greater than about pH 8; and
c) contacting an anti-CD3 or anti-CD28 activated T-cell with the MYC-containing polypeptide nanoparticle composition under conditions suitable for T-cell proliferation, augments one or more of the activation, survival, or proliferation of the T-cell compared with an anti-CD3 or anti-CD28 activated T-cell that is not contacted with the MYC polypeptide-containing composition; and
wherein the MYC-containing polypeptide comprises a MYC fusion protein, comprising a protein transduction domain linked to a MYC polypeptide.
2. The composition of claim 1 , wherein the nanoparticles have an average diameter of about 90-140 nm.
3. The composition of claim 1 , wherein the nanoparticles have an average diameter of between about 100 nm and about 110 nm.
4. The composition of claim 1 , wherein the nanoparticles have a molecular mass of about 10 4 -10 6 daltons.
5. The composition of claim 1 , wherein the nanoparticles comprise about 200 molecules of the MYC-containing polypeptide.
6. The composition of claim 1 , wherein the MYC polypeptide is acetylated.
7. The composition of claim 1 , wherein the MYC fusion peptide further comprises one or more linkers that link the protein transduction domain and the MYC polypeptide.
8. The composition of claim 1 , wherein the MYC-containing polypeptide comprises a MYC fusion peptide with the following general structure:
protein transduction domain-X-MYC sequence,
wherein -X- is a linker that links the protein transduction domain and the MYC sequence.
9. The composition of claim 1 , wherein the protein transduction domain sequence is a TAT protein transduction domain sequence.
10. The composition of claim 9 , wherein the TAT protein transduction domain sequence is selected from the group consisting of TAT[48-57] and TAT[57-48].
11. The composition of claim 1 , wherein the MYC polypeptide is a MYC fusion peptide comprising SEQ ID NO: 1 or 10.
12. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient.
13. The composition of claim 1 , formulated for topical administration, oral administration, parenteral administration, intranasal administration, buccal administration, rectal administration, or transdermal administration.