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Sequential Release of Pooled siRNAs and Paclitaxel by Aptamer-Functionalized Shell–Core Nanoparticles to Overcome Paclitaxel Resistance of Prostate Cancer
- Source :
- ACS Applied Materials & Interfaces. 13:13990-14003
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Paclitaxel (PTX) is a first-line chemotherapeutic agent to treat prostate cancer (PCa), but a large number of patients acquired drug resistance after short-term treatment. To develop combinational therapeutics to overcome PTX-resistant PCa, we established PTX-resistant LNCaP (LNCaP/PTX) cells and found that the LNCaP/PTX cells exhibited epithelial-mesenchymal transition (EMT) and enhanced metastasis during the selection process. We revealed that β-tubulin III, androgen receptor, and CXCR4 expressions were significantly increased in LNCaP/PTX cells and directly contributed to PTX resistance and EMT. Therefore, we developed prostate-specific membrane antigen aptamer (Apt)-functionalized shell-core nanoparticles (PTX/siRNAs NPs-Apt); the hydrophobic DSPE encapsulating PTX formed the dense inner core and the hydrophilic Apt-PEG2K with calcium phosphate (CaP) absorbing siRNAs formed the outer shell to sequentially release siRNAs and PTX, where CaP could trigger lysosomal escape to ensure that pooled siRNAs efficiently released into the cytoplasm to reverse EMT and resensitize PTX, while the PTX located in the core was subsequently released to exert the killing effect of chemotherapy to achieve the best synergistic effect. PTX/siRNAs NPs-Apt showed an enhanced tumor-targeting ability and achieved superior efficacy in the subcutaneous and orthotopic PCa tumor model with minimal side effects.
- Subjects :
- Male
0301 basic medicine
endocrine system
Small interfering RNA
Materials science
Paclitaxel
Aptamer
Mice, Nude
complex mixtures
Metastasis
03 medical and health sciences
Prostate cancer
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Cell Line, Tumor
LNCaP
medicine
Animals
Humans
General Materials Science
Epithelial–mesenchymal transition
RNA, Small Interfering
Drug Carriers
Mice, Inbred BALB C
Prostatic Neoplasms
medicine.disease
Antineoplastic Agents, Phytogenic
Androgen receptor
RNAi Therapeutics
030104 developmental biology
chemistry
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
Nanoparticles
Subjects
Details
- ISSN :
- 19448252 and 19448244
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- ACS Applied Materials & Interfaces
- Accession number :
- edsair.doi.dedup.....ea8d4428d7ae355b88c87854b353ba0e