Light-activatable polymeric nanoparticles
The present subject matter relates to light-activatable polymeric nanoparticles (NPs) for the transportation and release of an active substance, methods for obtain said particles and their uses. A light-activatable nanoparticle for the transportation and release of an active substance, comprising a polycation preferably a polimer polycation, a polyanion and a light-sensitive photochrome attached to the polycation or the polyanion, wherein said photochrome is hydrophobic and suitable to photo-cleave when activated by an irradiation source, generating a negative charge and releasing the active substance. Light-activatable. The disclosure subject matter shows that NPs are a highly efficient drug delivery system to primary leukemic cells based on opto-nanomedicine system. Therefore, the present disclosure is useful for remote control in the release of biomolecules with spatio-temporal resolution with applications in the areas of general therapeutic and regenerative medicine applications.
1. A light-activatable nanoparticle for the transportation and release of an active substance, comprising:
a polycation;
a polyanion;
and 4,5-dimethoxy-2-nitrobenzyl chloroformate as a light-sensitive photochrome attached to the polycation or the polyanion, wherein said photochrome is hydrophobic and suitable to photo-cleave when activated by an irradiation source.
2. The nanoparticle according to claim 1 , wherein said polycation is a polymer.
3. The nanoparticle according to claim 1 , wherein said polycationic polymer is selected from: poly(ethyleneimine), polylysine, poly(amino ester)s, poly(disulfide amines), chytosan, or combinations thereof.
4. The nanoparticle according to claim 1 , wherein the polyanion is selected from: dextran sulphate, polyaspartic acid, hyaluronic acid, or combinations thereof.
5. The nanoparticle according to claim 1 , wherein:
poly(ethyleneimine) (PEI) is the polycation; and
dextran sulphate is the polyanion.
6. The nanoparticle according to claim 5 , wherein the said active substance is selected from the group consisting of: a cellular modulation agent, a differentiating agent, a metabolic regulator, a cell cycle regulator, an epigenetic regulator, a reprogramming agent, a transcription factor, and combinations thereof.
7. The nanoparticle according to claim 6 , wherein the said active substance is retinoic acid.
8. The nanoparticle according to claim 7 , wherein molar ratio of DMNC to PEI is between 1% and 100%.
9. The nanoparticle according to claim 8 , wherein the final degree of substitutions PEI-DMNC is between 20-100%.
10. The nanoparticle according to claim 1 , wherein the average diameter of the nanoparticle is between 1-1000 nm.
11. The nanoparticle according to claim 1 , wherein said irradiation source is UV light or a blue laser.
12. A method of treatment of cancer diseases or for transfecting stem cells, comprising providing the nanoparticle according to claim 1 to a human.
13. A composition comprising a plurality of the nanoparticles of claim 1 , in a concentration of nanoparticle up to 100 μg/mL.
14. The composition according to claim 13 , wherein the composition is a topic formulation or an injectable formulation.
15. A method for obtaining a light-activatable polymeric nanoparticle, comprising the following steps:
derivatizing a polycation polymer with a light-sensitive hydrophobic photochrome in dimethyl sulfoxide, DMSO;
precipitating said polycation-photochrome solution into an aqueous solution comprising polyanion; and
separating the nanoparticles from the remaining polymers.
16. The method according to claim 15 , further comprising the following steps:
derivatizing poly(ethyleneimine) with 4,5-dimethoxy-2-nitrobenzyl chloroformate in DMSO, in presence of triethylamine;
precipitating PEI-DMNC solution into an aqueous solution of dextran sulphate.
17. The method according to claim 16 , further comprising adding zinc sulfate.
18. The nanoparticle according to claim 8 , wherein the final degree of substitutions PEI-DMNC is between 25-50%.
19. The nanoparticle according to claim 1 , wherein the average diameter of the nanoparticle is 160 nm.
20. The method of claim 15 , wherein the nanoparticles are separated from the remaining polymers by centrifugation or dialysis.