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Ionizable mesoporous silica nanoparticle-mediated siAURKB delivery for colorectal cancer therapy
Yuhao Yao1, Yuheng Leng1, Xilong Li1
1Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontier Science Center of the Materials Biology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. dapengzhang@ecust.edu.cn.
Abstract:
Colorectal cancer (CRC) is a common malignant tumor with high incidence and mortality worldwide. Conventional therapeutic strategies, such as surgical resection and chemotherapy, which result in improved outcomes for some patients, are greatly hindered by drug resistance and off-target toxicity. Small interfering RNA (siRNA)-mediated RNA interference has provided a breakthrough for precision CRC therapy. However, efficient delivery of siRNA to the tumor site with its complex tumor microenvironment remains challenging. Here, an ionizable mesoporous silica nanoparticle (MSN)-based nanocarrier with high siRNA loading capacity and enhanced cell membrane penetration capability is developed for effective CRC therapy. By modifying diethylamino groups onto the surface of MSNs featuring maze-like pores, a new siRNA delivery carrier, denoted as MPMNC, is successfully prepared. MPMNC exhibits improved cellular uptake efficiency in CT26 cells and a significant fluorescence silencing effect in EGFP-293T cells. Furthermore, aurora-B siRNA (siAURKB), which downregulates the expression of AURKB in tumor cells to induce apoptosis, is loaded onto MPMNC to afford the nanomedicine siAURKB@MPMNC, which delivers siAURKB to tumor cells and inhibits tumor growth effectively (tumor growth inhibition rate of 64.9%) through intratumor injection in CRC model mice. Additionally, it exhibits excellent biocompatibility in vitro and in vivo. Overall, this work presents a novel nanomedicine, siAURKB-loaded MSN, highlighting its surface modification with ionizable amino groups, which offers a promising therapeutic paradigm for CRC.
Insights
Researchers developed a novel mesoporous silica nanoparticle (MSN) carrier for precise colorectal cancer (CRC) therapy. This nanomedicine effectively delivers small interfering RNA (siRNA) to inhibit tumor growth with excellent biocompatibility.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Colorectal cancer (CRC) presents significant global health challenges due to high incidence and mortality.
- Conventional treatments like chemotherapy face limitations including drug resistance and toxicity.
- Small interfering RNA (siRNA) offers potential for targeted CRC therapy, but efficient delivery remains a hurdle.
Purpose of the Study:
- To develop an advanced nanocarrier for effective siRNA delivery in colorectal cancer.
- To enhance siRNA loading capacity and cell membrane penetration for improved therapeutic efficacy.
- To create a novel nanomedicine for precise and safer colorectal cancer treatment.
Main Methods:
- Ionizable mesoporous silica nanoparticles (MSNs) were surface-modified with diethylamino groups to create MPMNC.
- MPMNC demonstrated enhanced cellular uptake in CT26 cells and gene silencing in EGFP-293T cells.
- Aurora-B siRNA (siAURKB) was loaded onto MPMNC to form siAURKB@MPMNC for intratumoral injection in CRC mouse models.
Main Results:
- The developed MPMNC carrier showed high siRNA loading and improved cell penetration.
- siAURKB@MPMNC significantly inhibited tumor growth in CRC model mice, achieving a 64.9% inhibition rate.
- The nanomedicine exhibited excellent biocompatibility both in vitro and in vivo.
Conclusions:
- This study presents a novel ionizable MSN-based nanocarrier (MPMNC) for effective siRNA delivery in colorectal cancer.
- The developed nanomedicine, siAURKB@MPMNC, offers a promising therapeutic strategy for CRC by inducing tumor cell apoptosis.
- Surface modification of MSNs with ionizable amino groups represents a viable approach for advancing precision cancer therapy.
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