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Transcriptional downregulation of these genes offers a promising therapeutic strategy for cancer treatment by inducing apoptosis. Reducing expressions of these genes by RNA interference\u2010mediated silencing is a potential strategy for more effective gene suppression. The research developed a novel protamine biopolymer\u2010modified GSH\u2010responsive biodegradable mesoporous silica nanoparticle system to suppress MCL\u20101 and Survivin genes' transcriptional activity in MCF\u20107 tumor\u2010bearing mice. The nanocarriers were characterized using techniques like DLS, XRD, FTIR, GSH\u2010utilization, SEM, and TEM. The nanocarriers were tested for their ability to deliver siRNAs into target cells, and their toxic behavior was assessed in vitro and in vivo. The nanocarriers' gene silencing and anti\u2010cancer efficacy were assessed in both in vitro and in vivo models. The study revealed that synthesized MUC1 aptamer\u2010conjugated protamine\u2010modified nanocarriers (MPPM) offer stability to siRNAs, target MCF\u20107 tumor, and induce apoptosis with dual siRNAs. Additionally, the MPPM nanocarrier demonstrated significant potential for targeting the MCF\u20107 tumor in the mice model, and the histological findings suggested its biosafety profile. The siMCL\u20101\/siSur@MPPM nanocarriers demonstrated a significant anti\u2010tumor effect in an in vivo mice model through the silencing of target genes and the induction of apoptosis. These results indicate that the biodegradable siMCL\u20101\/siSur@MPPM nanocarrier provides a significant combination of targeted delivery, biodegradability, effective gene silencing, and reduced off\u2010target effects, suggesting its potential as a promising nanomedicine for breast cancer treatment.<\/jats:p>","DOI":"10.1002\/adhm.202505296","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:05:48Z","timestamp":1775736348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multitalented Hybrid Targeted Nanoconstructs Selectively Repress Survival Genes and Induce Breast Tumor Regression In Vivo"],"prefix":"10.1002","volume":"15","author":[{"given":"Niladri","family":"Haldar","sequence":"first","affiliation":[{"name":"Nanobioscience, Agharkar Research Institute  Pune India"},{"name":"Savitribai Phule Pune University  Pune 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