Combined Multimodal Optical Imaging and Targeted Gene Silencing Using Stimuli-Transforming Nanotheragnostics

Abstract

Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interference RNA (siRNA)-encapsulating polyplexes were covalently coated with small gold nanoparticles (Au NPs) via acid-cleavable linkages in order to explore the possibility of achieving combined stimuli-responsive multi-modal optical imaging and stimuli-enhanced gene silencing. In a mildly acidic tumor environment, Au NPs are dissociated from the siRNA-carrying polyplexes, generating various optical signal changes such as diminished scattering intensity, increased variance of Doppler frequency, and blue-shifted UV absorbance (stimuli-responsive imaging). Simultaneously, Au NP dissociation exposes the siRNA-carrying polyplex with elevated surface charge and results in enhanced cellular uptake and transfection (stimuli-enhanced therapy). In this study, the feasibility of achieving combined diagnosis and therapy for cancer (theragnostics) is demonstrated by 1) microscopic and spectrophotometric confirmation of acid-transformation of the nanoparticles, 2) reduced scattering intensity and increased variance of Doppler frequency in an acidic pH upon the nanoparticle’s transformation, and 3) simultaneous optical signal changes and gene silencing in vitro under a tumor pH-mimicking condition. This novel type of stimuli-responsive nanotheragnostics will provide a new paradigm for pinpointed, multi-modal, and combined imaging and therapy for cancer.

Rigid nanoparticle-based delivery of anti-cancer siRNA: Challenges and opportunities

“…Shim et al demonstrated the feasibility of achieving combined diagnosis and gene therapy for cancer based on gold nanovector with the SPR effect (Figure 5) (Shim et al, 2010). The nanovehicle was developed through acid responsive ketalized linear PEI encapsulated on the gold nanoparticles.…”

The intracellular plasmid DNA localization of cationic reducible cholesterol-disulfide lipids

“…Due to the overwhelming advantages in biological safety, synthetic non-viral gene delivery carriers include cationic lipids [1e7], amphiphilic polymers [8e14] as well as functional nanoparticles [15,16] have been intensively explored in vitro and in vivo, and these synthetic vectors for delivering therapeutic DNA, small interfering RNA (RNAi) and oligomer DNA (ODNA) have been investigated to show strong molecular structure/architecture dependence of nucleic-acid binding, encapsulation and release in cells, and breaking up the correlation between cytotoxicity and transgenetic efficacy becomes a current challenge in molecular design of artificial-viral gene carriers [17].…”

On-line Ammonia Sensor and Invisible Security Ink by Fluorescent Zwitterionic Spirocyclic Meisenheimer Complex

“…These materials have already been applied in different purposes like fabrication of detector, sensing device, thermal imaging, memory and display devices1112131415. Different classes of fluorescent molecules have so far been designed and synthesized in such a way that they can be used as a fluorescent switch using external stimuli like pH, light, metal ions, redox potential, temperature and vapours etc1617181920212223. In recent decade with the increment of cyber theft, data recording and storage in a secured way has become crucial in economic as well as military fields.…”