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Multitalented Hybrid Targeted Nanoconstructs Selectively Repress Survival Genes and Induce Breast Tumor Regression In
Niladri Haldar1,2, Rajkumar Samanta1,2, Surajit Patra1,2
1Nanobioscience, Agharkar Research Institute, Pune, India.
Advanced Healthcare Materials
|April 9, 2026
Summary
This study introduces a novel nanoparticle system for breast cancer therapy. The system effectively silences key survival genes (MCL-1 and Survivin) in tumor cells, leading to apoptosis and significant anti-tumor effects in mice.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Dysregulation of survival genes (e.g., MCL-1, Survivin) is crucial in breast cancer development.
- Transcriptional downregulation of these genes via RNA interference offers a therapeutic strategy by inducing apoptosis.
- Effective gene suppression requires advanced delivery systems for enhanced efficacy and reduced side effects.
Purpose of the Study:
- To develop and evaluate a novel protamine biopolymer-modified, GSH-responsive, biodegradable mesoporous silica nanoparticle system.
- To investigate the system's ability to suppress MCL-1 and Survivin gene expression in MCF-7 breast cancer cells.
- To assess the in vitro and in vivo anti-cancer efficacy and biosafety of the developed nanocarrier system.
Main Methods:
- Synthesis and characterization of protamine-modified, MUC1 aptamer-conjugated, GSH-responsive silica nanoparticles (MPPM).
- Loading of siRNAs targeting MCL-1 and Survivin genes into the nanocarriers (siMCL-1/siSur@MPPM).
- In vitro and in vivo evaluation of siRNA delivery, gene silencing, apoptosis induction, anti-tumor efficacy, and biosafety in MCF-7 tumor-bearing mice.
Main Results:
- The MPPM nanocarriers demonstrated stability, targeted delivery to MCF-7 tumors, and effective siRNA loading.
- siMCL-1/siSur@MPPM induced significant gene silencing of MCL-1 and Survivin, leading to apoptosis in cancer cells.
- In vivo studies showed a significant anti-tumor effect, with histological findings indicating a favorable biosafety profile.
Conclusions:
- The biodegradable siMCL-1/siSur@MPPM nanocarrier system offers targeted delivery, efficient gene silencing, and biodegradability for breast cancer treatment.
- This nanomedicine demonstrates potential for effective cancer therapy by inducing apoptosis and reducing off-target effects.
- The developed system shows promise as a novel therapeutic approach for managing breast cancer.
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