Spherical Nucleic Acids for Near-Infrared Light-Responsive Self-Delivery of Small-Interfering RNA and Antisense Oligonucleotide

Abstract

Herein, we developed a photolabile spherical nucleic acid (PSNA) for carrier-free and near-infrared (NIR) photocontrolled self-delivery of small-interfering RNA (siRNA) and antisense oligonucleotide (ASO). PSNA comprised a hydrophilic siRNA shell with a hydrophobic core containing a peptide nucleic acid-based ASO (pASO) and NIR photosensitizer (PS). The incorporation of a singlet oxygen (1O2)-cleavable linker between the siRNA and pASO allowed on-demand disassembly of PSNA in tumor cells once 1O2 was produced by the inner PS upon NIR light irradiation. The generated 1O2 could also concurrently promote lysosomal escape of the released siRNA and pASO to reach cytosolic targets. Both in vitro and in vivo results demonstrated that, under NIR light irradiation, PSNA could suppress hypoxia inducible factor-1α (HIF-1α) and B-cell lymphoma 2 (Bcl-2) for gene therapy (GT), which further combined photodynamic therapy (PDT) favored by the released PS to inhibit tumor cell growth. Given its carrier-free, NIR-sensitive, designable, and biocompatible merits, PSNA represents a promising self-delivery nanoplatform for cancer therapy.

Transdermal delivery of poly-hyaluronic acid-based spherical nucleic acids for chemogene therapy

“…2b and c and S5†) that PHAA based nanoparticles achieve non-colocalization with lysosomes, there may be some related mechanisms, such as endosomal leaking, reverse vesicle fusion, inclusion body-Golgi vesicle transport and so on. 51–54 Overall, the above results demonstrated that PHA-based SNA nanoparticles showed effective ASO delivery and good improvement of cell uptake.…”

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies

“…For example, Chen et al prepared a photolabile spherical nucleic acid for light-responsive codelivery of antisense oligonucleotide and siRNA. Upon exposure to an NIR laser, the prepared nanoplatforms rapidly oxidized and dissociated with continuous responsive release, resulting in a positive effect on tumor treatment [ 400 ]. Xu et al designed a light stimuli-responsive nanoparticle to achieve long blood circulation, enhanced tumor accumulation and penetration, and rapid body elimination in an imaging-guided treatment.…”

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

“…Recently, a photolabile spherical nucleic acid for carrier-free and near-infrared photo-controlled self-delivery of small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) was also published. By incorporating a thioketal linker between the SiRNA and the peptide nucleic acid-based ASO, on-demand disassembly of photolabile spherical nucleic acid in tumors cells is possible once the 1 O 2 is produced by the inner PS upon NIR irradiation [ 198 ]. Furthermore, nanoparticle type vehicles also have been functionalized with a ROS cleavable linker in order to obtain light-triggered drug release (see Figure 13 ) [ 199 , 200 , 201 , 202 , 203 ].…”