Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in
Zongguang Tai1,2, Jinyuan Ma1, Jianing Ding1
1Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People's Republic of China.
Purpose:
The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells.
Materials And Methods:
An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.
Results:
The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.
Conclusion:
PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.
Insights
This study developed a novel nanoparticle delivery system for long non-coding RNA (lncRNA) gene therapy in castration-resistant prostate cancer (CRPC). The system efficiently delivered tumor suppressor lncRNA MEG3, showing significant anti-CRPC effects in vitro and in vivo.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Gene Therapy
Background:
- Castration-resistant prostate cancer (CRPC) presents significant clinical management challenges.
- Traditional CRPC treatments have adverse effects, prompting research into novel therapies like gene therapy.
- The therapeutic potential of long non-coding RNAs (lncRNAs) in CRPC gene therapy is promising but underexplored due to delivery limitations.
Purpose of the Study:
- To investigate the efficacy of a novel nanoparticle-based delivery system for lncRNA gene therapy in CRPC.
- To evaluate the delivery of plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) into CRPC cells using a targeted nanoparticle system.
Main Methods:
- Developed EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimers for targeted delivery of pMEG3 to CRPC cells.
- Created PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) for efficient lncRNA delivery.
- Conducted in vitro cellular assays (uptake, entry, CCK-8) and in vivo studies (tumor growth inhibition, histology, safety) to assess NP efficacy.
Main Results:
- The EpDT3 aptamer significantly enhanced the endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells.
- PAMAM-PEG-EpDT3/pMEG3 NPs demonstrated a significant anti-CRPC effect in both in vitro and in vivo models.
- The targeted NPs showed superior efficacy compared to unfunctionalized PAMAM-PEG/pMEG3 NPs.
Conclusions:
- PAMAM-PEG-EpDT3/pMEG3 nanoparticles represent a promising strategy for enhancing gene therapy in CRPC.
- This targeted delivery system holds potential for improving the clinical management of CRPC through advanced gene therapy approaches.
