Coordinated modulation of long non-coding RNA ASBEL and curcumin co-delivery through multicomponent nanocomplexes for synchronous triple-negative breast cancer theranostics

Abstract

Background Abnormally regulated long non-coding RNAs (lncRNAs) functions in cancer emphasize their potential to serve as potential targets for cancer therapeutic intervention. LncRNA ASBEL has been identified as oncogene and an anti-sense transcript of tumor-suppressor gene of BTG3 in triple-negative breast cancer (TNBC). Results Herein, multicomponent self-assembled polyelectrolyte nanocomplexes (CANPs) based on the polyelectrolytes of bioactive hyaluronic acid (HA) and chitosan hydrochloride (CS) were designed and prepared for the collaborative modulation of oncogenic lncRNA ASBEL with antago3, an oligonucleotide antagonist targeting lncRNA ASBEL and hydrophobic curcumin (Cur) co-delivery for synergetic TNBC therapy. Antago3 and Cur co-incorporated CANPs were achieved via a one-step assembling strategy with the cooperation of noncovalent electrostatic interactions, hydrogen-bonding, and hydrophobic interactions. Moreover, the multicomponent assembled CANPs were ulteriorly decorated with a near-infrared fluorescence (NIRF) Cy-5.5 dye (FCANPs) for synchronous NIRF imaging and therapy monitoring performance. Resultantly, MDA-MB-231 cells proliferation, migration, and invasion were efficiently inhibited, and the highest apoptosis ratio was induced by FCANPs with coordination patterns. At the molecular level, effective regulation of lncRNA ASBEL/BTG3 and synchronous regulation of Bcl-2 and c-Met pathways could be observed. Conclusion As expected, systemic administration of FCANPs resulted in targeted and preferential accumulation of near-infrared fluorescence signal and Cur in the tumor tissue. More attractively, systemic FCANPs-mediated collaborative modulating lncRNA ASBEL/BTG3 and Cur co-delivery significantly suppressed the MDA-MB-231 xenograft tumor growth, inhibited metastasis and extended survival rate with negligible systemic toxicity. Our present study represented an effective approach to developing a promising theranostic platform for combating TNBC in a combined therapy pattern.

Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy

“…In contrast, non-viral vectors have attracted widespread attention due to high safety, nonimmunogenicity, non-infectious, unlimited vector capacity, large-scale preparation, low cost, and targeting, which are also an indispensable class of efficient carriers in the field of gene therapy [13][14][15][16]. With the rapid development of nanotechnology, various organic and inorganic nanomaterials are used as carriers for drug and gene delivery, such as chitosan nanoparticles (NPs) [17][18][19], lipid-based NPs [20,21], polymer NPs [22][23][24], gold NPs [25,26], magnetic NPs [27], quantum dots (QDs) [28,29], silica NPs [30,31], and carbon nanomaterials [32,33] (Table 1). Among these non-viral vectors, iron-based nanomaterials possess both nanometer effects and superparamagnetism.…”