Certain cancers, such as triple‐negative breast cancer (TNBC), pose a challenging prognosis due to the absence of identifiable hormone‐related receptors and effective targeted therapies. Consequently, novel therapeutics are required for these cancers, offering minimal side effects and reduced drug resistance. Unexpectedly, siRNA‐7, initially employed as a control, exhibited significant efficacy in inhibiting cell viability in MDA‐MB‐231 cells. Through a genome‐wide search of seed sequences, the targets of siRNA‐7 were identified as cancer‐related genes, namely PRKCE, RBPJ, ZNF737, and CDC7 in MDA‐MB‐231 cells. The mRNA repression analysis confirmed the simultaneous suppression by siRNA‐7. Combinatorial administration of single‐targeting siRNAs demonstrated a comparable reduction in viability to that achieved by siRNA‐7. Importantly, siRNA‐7 selectively inhibited cell viability in MDA‐MB‐231 cells, while normal HDF‐n cells remained unaffected. Furthermore, in a xenograft mouse model, siRNA‐7 exhibited a remarkable 76% reduction in tumor volume without any loss in body weight. These findings position siRNA‐7 as a promising candidate for a novel, safe, specific, and potent TNBC cancer therapeutic. Moreover, the strategy of multiple suppressing small interfering RNA holds potential for the treatment of various diseases associated with gene overexpression.
Breast cancer is one of the serious diseases and has the second-highest
mortality in women worldwide. RNA interference has been developed as a
promising way of specific cancer treatment by silencing oncogenes
efficiently. However, small RNAs exhibits difficulties in specific
cellular uptake and instability. Therefore, we designed novel fusion
peptides (RS and RT) for an efficient, stable, and specific delivery of
small RNAs. Both RS and RT peptides could form self-assembled
nanocomplexes via electrostatic attraction. RS nanocomplexes exhibited
prolonged stability, enhanced cellular uptake, and target gene silencing
by siRNAs to MDA-MB-231 breast cancer cells. Moreover, RS nanocomplexes
successfully inhibited breast cancer cell growth via specific and
efficient siRNA delivery. Furthermore, in vitro and in vivo safety tests
showed negligible cytotoxicity and neither tissue damage nor significant
inflammatory cytokine release. Therefore, the RS nanocomplexes could be
expected to become a promising siRNA delivery platform for the treatment
of breast cancer or other cancers.
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