Self-assembled fluorescent hybrid nanoparticles-mediated collaborative lncRNA CCAT1 silencing and curcumin delivery for synchronous colorectal cancer theranostics

Abstract

Background Cancer synergistic therapy strategy in combination with therapeutic gene and small molecule drug offers the possibility to amplify anticancer efficiency. Colon cancer-associated transcript-1 (CCAT1) is a well identified oncogenic long noncoding RNA (lncRNA) exerting tumorigenic effects in a variety of cancers including colorectal cancer (CRC). Results In the present work, curcumin (Cur) and small interfering RNA targeting lncRNA CCAT1(siCCAT1) were co-incorporated into polymeric hybrid nanoparticles (CSNP), which was constructed by self-assembling method with two amphiphilic copolymers, polyethyleneimine-poly (d, l-lactide) (PEI-PDLLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) (DSPE-mPEG). Owing to the multicolor fluorescence characteristics of PEI-PDLLA, the constructed CSNP could be served as a theranostic nanomedicine for synchronous therapy and imaging both in vitro and in vivo. Resultantly, proliferation and migration of HT-29 cells were efficiently inhibited, and the highest apoptosis ratio was induced by CSNP with coordination patterns. Effective knockdown of lncRNA CCAT1 and concurrent regulation of relevant downstream genes could be observed. Furthermore, CSNP triggered conspicuous anti-tumor efficacy in the HT-29 subcutaneous xenografts model with good biosafety and biocompatibility during the treatment. Conclusion On the whole, our studies demonstrated that the collaborative lncRNA CCAT1 silencing and Cur delivery based on CSNP might emerge as a preferable and promising strategy for synergetic anti-CRC therapy. Graphic abstract

Lactoferrin-Based Ternary Composite Nanoparticles with Enhanced Dispersibility and Stability for Curcumin Delivery

“…The results showed that the proportion of total apoptotic cells in HT-29 and CT-26 cells treated with Cur-LF-EGCG-HA nanoparticles was significantly higher than that of LF-EGCG-HA nanoparticles and Free Cur, indicating that the curcumin-loaded nanoparticles promoted the apoptosis of two colorectal cancer cell lines, which was consistent with the results of MTT. Researchers have reported that curcumin, in response to the expression of Bcl-2 and Caspase-3, can induce apoptosis in a variety of cancer cells, including colorectal cancer cells . Cai et al also showed that doxorubicin encapsulated in nanoparticles can enhance doxorubicin-induced cytotoxicity.…”

“…Researchers have reported that curcumin, in response to the expression of Bcl-2 and Caspase-3, can induce apoptosis in a variety of cancer cells, including colorectal cancer cells. 58 Cai et al 59 also showed that doxorubicin encapsulated in nanoparticles can enhance doxorubicin-induced cytotoxicity. Notably, the proportion of total apoptotic cells in HT-29 cells treated with LF-EGCG-HA nanoparticles was significantly higher than free curcumin, possibly due to the toxic effects of EGCG and LF in LF-EGCG-HA nanoparticles on HT-29 cells.…”

Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies

“…Furthermore, in order to silence the oncogenic activity of CCAT1 lncRNA, siCCAT1 was conjugated to polymeric hybrid nanoparticles (CSNP). In this way, it was possible to obtain a good anti-tumor effect in the HT-29 subcutaneous xenograft model of colorectal cancer [89]. Finally, by exploiting the enhanced permeability and retention (EPR) effect, Bi et al were able to deliver NPs loaded with siAFAP1-AS1 to the tumor site.…”

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications

“…Curcumin combined with si-MALAT1 could significantly reduce its expression and inhibit the cell activity, migration, and invasion of SW480 (colorectal cancer cell) [ 127 ]. Through polymeric hybrid nanoparticles (CSNPs), combining curcumin with siCCAT1 (Lnc CCAT1 small interfering RNA) could effectively inhibit the proliferation and migration of HT-29 cells (colorectal cancer cells) and induce a high apoptosis rate in a synergistic manner [ 128 ]. Hence, nanoparticles packaged with overexpressed/silenced Lnc RNAs and collaboratively transported with curcumin may provide a better and more promising strategy for colorectal cancer treatment.…”