Back to Search
Start Over
Smart nanoparticles with a detachable outer shell for maximized synergistic antitumor efficacy of therapeutics with varying physicochemical properties
- Source :
- Journal of Controlled Release. 243:54-68
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Co-delivery systems capable of transporting hydrophobic chemotherapeutics and hydrophilic siRNA to the same cell population with simultaneous burst release of both drugs to maximize synergistic anticancer efficacy remains elusive. In this light, a multifunctional nanoparticle (HA-PSR) consisting of a redox-sensitive core and detachable crosslinked hyaluronic acid (HA) shell was developed. Octyl modified PEI containing disulfide linkages (PSR) were synthesized as the core materials for co-encapsulation of chemotherapeutics and siRNA, while a HAase-sensitive thiolated HA (HA-SH) was collaboratively assembled to the anionic shell for CD44-mediated active targeting along with enhanced and detachable protection for drug loaded inner cores. Resultantly, HA de-protected redox-sensitive inner cores achieved co-burst release of both cargoes when triggered by glutathione (GSH) rich environments in cytoplasm. Results of in-vivo and in-vitro testing indicated successful co-encapsulation of hydrophobic drugs and hydrophilic siRNA with adjustable ratios. Selective delivery to CD44 overexpressing tumors was achieved through passive and active targeting, followed by HAase-triggered HA de-shielding and GSH-triggered burst release of both cargos. Rapid intracellular trafficking maximized synergistic cytotoxicities of chemotherapeutics and siRNA for remarkable tumor inhibition in a xenograft animal tumor model. Consequently, the HA-PSR nanoparticle holds great potential for combined chemotherapeutics/siRNA treatment in cancer with maximized synergistic antitumor efficacy.
- Subjects :
- Drug
THP-1 Cells
Chemistry, Pharmaceutical
media_common.quotation_subject
Population
Multifunctional nanoparticles
Cell
Mice, Nude
Pharmaceutical Science
Nanoparticle
Antineoplastic Agents
02 engineering and technology
Pharmacology
010402 general chemistry
01 natural sciences
chemistry.chemical_compound
Drug Delivery Systems
Neoplasms
Hyaluronic acid
medicine
Animals
Humans
Polyethyleneimine
Hyaluronic Acid
RNA, Small Interfering
education
media_common
Drug Carriers
Mice, Inbred BALB C
education.field_of_study
Chemistry
Drug Synergism
Glutathione
021001 nanoscience & nanotechnology
Xenograft Model Antitumor Assays
0104 chemical sciences
Hyaluronan Receptors
medicine.anatomical_structure
Biophysics
Nanoparticles
Female
0210 nano-technology
Hydrophobic and Hydrophilic Interactions
Intracellular
Subjects
Details
- ISSN :
- 01683659
- Volume :
- 243
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release
- Accession number :
- edsair.doi.dedup.....2c23e0a4519589f07f80fd4d3d8a3256