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Biocompatible AIEgen/p-glycoprotein siRNA@reduction-sensitive paclitaxel polymeric prodrug nanoparticles for overcoming chemotherapy resistance in ovarian cancer
- Source :
- Theranostics
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- Nanoparticle drug delivery system (NDDS) is quite different from the widely studied traditional chemotherapy which suffers from drug resistance and side effect. NDDS offers the straightforward solution to the chemotherapy problem and provides an opportunity to monitor the drug delivery process in real time. In this vein, we developed one NDDS, namely Py-TPE/siRNA@PMP, to relieve resistance and side effects during chemotherapy against ovarian cancer. The Py-TPE/siRNA@PMP is a multifunctional polymeric nanoparticle contained several parts as follows: (1) a nanoparticle (NP) self-assembled by reduction-sensitive paclitaxel polymeric prodrug (PMP); (2) the glutathione (GSH)-responsive release of paclitaxel (PTX) for the suppression of ovarian cancer cells; (3) the P-glycoprotein (P-gp) siRNA for restoring the sensitivity of chemo-resistant tumor cells to chemotherapy; (4) the positively charged aggregation-induced emission fluorogen (AIEgen) Py-TPE for tumor imaging and promoting encapsulation of siRNA into the nanoparticle. Methods: The Py-TPE/siRNA@PMP nanoparticles were prepared by self-assembly method and characterized by the UV-Vis absorption spectra, zeta potentials, TEM image, stability assay and hydrodynamic size distributions. The combinational therapeutic effects of Py-TPE/siRNA@PMP on overcoming chemotherapy resistance were explored both in vitro and in vivo. Result: The Py-TPE/siRNA@PMP exhibited an average hydrodynamic size with a good stability. Meanwhile they gave rise to the remarkable chemotoxicity performances in vitro and suppressed the tumors growth in both SKOV-3/PTX (PTX resistance) subcutaneous and intraperitoneal metastasis tumor models. The investigations on ovarian cancer patient-derived xenografts (PDX) model revealed that Py-TPE/siRNA@PMP was able to effectively overcome their chemo-resistance with minimal side effects. Conclusion: Our findings demonstrated the Py-TPE/siRNA@PMP as a promising agent for the highly efficient treatment of PTX-resistant cells and overcoming the shortage of chemotherapy in ovarian cancer.
- Subjects :
- chemotherapy resistance
aggregation-induced emission
medicine.medical_treatment
Medicine (miscellaneous)
Biocompatible Materials
02 engineering and technology
Drug resistance
Multifunctional Nanoparticles
01 natural sciences
chemistry.chemical_compound
Mice
Drug Delivery Systems
p-glycoprotein
Materials Testing
Prodrugs
Precision Medicine
RNA, Small Interfering
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
P-glycoprotein
Ovarian Neoplasms
Mice, Inbred BALB C
biology
021001 nanoscience & nanotechnology
ovarian cancer
Paclitaxel
Drug delivery
Female
0210 nano-technology
Research Paper
Side effect
Mice, Nude
010402 general chemistry
In vivo
Cell Line, Tumor
medicine
Animals
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Chemotherapy
medicine.disease
Antineoplastic Agents, Phytogenic
Xenograft Model Antitumor Assays
0104 chemical sciences
chemistry
Drug Resistance, Neoplasm
drug delivery
biology.protein
Cancer research
Ovarian cancer
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 11
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....6e62f88292e8a75e746592817b0af2be