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

Xiongwei Deng,Zian Pan,Yan Wu,Yunhao Li,Fan Jia,Xinyue Cui,Xuan Wang,Jianqing Lu

doi:10.1186/s12951-021-00981-7

Abstract

BackgroundCancer 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).ResultsIn 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.ConclusionOn 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

Highlights

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer in both male and female [1]
Construction and characterization of the co‐delivery system The Cur-siCCAT1-co-loaded NP (CSNP) The amphiphilic copolymer PEI-PDLLA was prepared according to the ring-opening polymerization method, which was reported by our laboratory formerly [43]
Fourier transform infrared spectroscopy (FT-IR) analysis showed a peak at 1663 cm−1 corresponding to PEI, and the strong absorption peak at 1757 cm−1 corresponding to PDLLA (Additional file 1: Fig. S1). 1H nuclear magnetic resonance (1H NMR) in C DCl3 as shown in Additional file 1: Fig. S2, the signal at 2.1 ~ 3.5 ppm in PEI-PDLLA assigned to PEI (–NHCH2CH2–), indicating that the hydrophilic PEI backbone was linked to the hydrophobic PDLLA successfully

Summary

Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer in both male and female [1]. Colon cancer-associated transcript-1 (CCAT1), a recently identified oncogenic lncRNA, which maps to chromosome 8q24.21 containing single-nucleotide polymorphisms with a length of 2628 nucleotides, has been reported to be continuously raised in a variety of cancer tissues, especially in CRC [10,11,12,13]. Comparing to protein-coding genes, lncRNAs do not encode the protein, and their effect would emerge shortly after delivery and might lead to fewer side-effects [21,22,23] For this reason, lncRNAs can be operated by RNA interference (RNAi) or other means with ease. 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)

Methods

Results

Conclusion