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Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy.
Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy.
- Source :
-
ACS nano [ACS Nano] 2017 Mar 28; Vol. 11 (3), pp. 2618-2627. Date of Electronic Publication: 2017 Mar 03. - Publication Year :
- 2017
-
Abstract
- With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery. A library of oligoarginine-functionalized and sharp pH-responsive polymers was synthesized and used for self-assembly with siRNA into NPs with the features of long blood circulation and pH-triggered oligoarginine-mediated endosomal membrane penetration. By further modification with ACUPA, a small molecular ligand specifically recognizing prostate-specific membrane antigen (PSMA) receptor, this envelope-type nanoplatform with multifunctional properties can efficiently target PSMA-expressing PCa cells and silence target gene expression. Systemic delivery of the siRNA NPs can efficiently silence the expression of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers, and significantly inhibit PCa tumor growth. These results suggest that this multifunctional envelope-type nanoplatform could become an effective tool for PCa-specific therapy.
- Subjects :
- Animals
Antigens, Surface metabolism
Antineoplastic Agents chemistry
Cell Proliferation drug effects
Gene Silencing
Glutamate Carboxypeptidase II antagonists & inhibitors
Glutamate Carboxypeptidase II metabolism
Glutarates chemistry
HeLa Cells
Humans
Hydrogen-Ion Concentration
Ligands
Male
Mice
Mice, Nude
Molecular Structure
Neoplasms, Experimental drug therapy
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Particle Size
Prohibitins
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
RNA, Small Interfering chemistry
RNA, Small Interfering genetics
Small Molecule Libraries chemistry
Surface Properties
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Gene Transfer Techniques
Nanoparticles chemistry
Prostatic Neoplasms drug therapy
RNA, Small Interfering pharmacology
Small Molecule Libraries pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 11
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 28240870
- Full Text :
- https://doi.org/10.1021/acsnano.6b07195