Shape-directed compartmentalized delivery of a nanoparticle-conjugated small-molecule activator of an epigenetic enzyme in the brain.
Targeted drug delivery to specific subcellular compartments of brain cells is challenging despite their importance in the treatment of several brain-related diseases. Herein, we report on shape-directed intracellular compartmentalization of nanoparticles in brain cells and their ability to deliver therapeutic molecules to specific organelles. Iron oxide (Fe3O4) nanoparticles with different morphologies (spheres, spindles, biconcaves, and nanotubes) were synthesized and coated with a fluorescent carbon layer derived from glucose (Fe3O4@C). In vivo studies showed that the Fe3O4@C nanoparticles with biconcave geometry localized predominantly in the nuclei of the brain cells, whereas those with nanotube geometry were contained mostly in the cytoplasm. Remarkably, a small-molecule activator of histone acetyltransferases delivered into the nuclei of the brain cells using nanoparticles with biconcave geometry showed enhancement in enzymatic activity by a factor of three and resulted in specific gene expression (transcription) compared with that of the molecule delivered to the cytoplasm using nanotube geometry.
Nanomaterials and Catalysis Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Piyush
P
Chaturbedy
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Manoj
M
Kumar
Nanomaterials and Catalysis Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Krishnachary
K
Salikolimi
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Sadhan
S
Das
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Sarmistha Halder
SH
Sinha
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
Snehajyoti
S
Chatterjee
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India.
B S
BS
Suma
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India. Electronic address: tapas@jncasr.ac.in.
Tapas K
TK
Kundu
Nanomaterials and Catalysis Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560 064, India. Electronic address: eswar@jncasr.ac.in.
Muthusamy
M
Eswaramoorthy
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000737:chemistry; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008807:Mice, Inbred BALB C; D043942:Nanotubes / Q000737:chemistry; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D001549:Benzamides; D005290:Ferric Compounds; D005947:Glucose; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000499:ferric oxide
Brain targeting; Compartmentalized drug delivery; Nanocomposites; Nanomedicine; Physicochemical property