Atom Transfer Radical Polymerization of Multishelled Cationic Corona for the Systemic Delivery of siRNA

Abstract

We propose an effective siRNA delivery system by preparing poly(DAMA-HEMA)-multilayered gold nanoparticles using multiple surface-initiated atom transfer radical polymerization processes. The polymeric multilayer structure is characterized by transmission electron microscopy, matrix-associated laser desorption/ionization time-of-flight mass spectrometry, UV-vis spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and ζ-potential. The amount of siRNA electrostatically incorporated into the nanoparticle can be tuned by the number of polymeric shells, which in turn influences the cellular uptake and gene silencing effect. In a bioreductive environment, the interlayer disulfide bond breaks to release the siRNA from the degraded polymeric shells. Intravenously injected c-Myc siRNA-incorporated particles accumulate in the tumor site of a murine lung carcinoma model and significantly suppress the tumor growth. Therefore, the combination of a size-tunable AuNP core and an ATRP-functionalized shell offers control and versatility in the effective delivery of siRNA.

Surface-Initiated Atom Transfer Radical Polymerization for the Preparation of Well-Defined Organic–Inorganic Hybrid Nanomaterials

“…The organic polymer layer covering the metallic core of the gold nanoparticles leads to the creation of hybrid materials, which can be used as a molecular diagnostic tool as well as element of the drug delivery system, hence the wide interest in the modification of such nanoparticles exhibiting high application ability in biomedical fields. It is worth noting that intensified research on the modification of gold nanoparticles in recent years effected in simple modifications [63] through a core–shell structure of gold NPs [64] or even advanced biomedical applications such as the SiRNA delivery system reported in 2018 [52].…”

“…The ability to synthesize polymer brushes on the surface of nanoparticles (e.g., gold (Au) [51,52], silver (Ag) [53], silica (Si) [35,54], titanium (Ti) [55], cobalt (Co) [56], and zinc (Zn) [39]) via the SI-ATRP approach provides efficient tool that can be applied in a wide range of engineering applications such as a membrane technology [57] as well as biomedical applications [56,58,59,60] including immunotherapy [61] and antifouling surfaces [62].…”

Therapeutics for Inflammatory-Related Diseases Based on Plasmon-Activated Water: A Review

“…Since gold nanoparticles (AuNPs) possess well-defined localized surface plasmon resonance (LSPR) bands in the UV–near infrared (IR) regions, they are commonly used in surface-enhanced Raman scattering (SERS) for improved diagnostic imaging [ 1 , 2 , 3 ] and in photothermal ablation of tumors [ 4 , 5 , 6 ]. Recently, AuNPs have been widely utilized in innovatively therapeutic strategies on various cancers [ 7 , 8 , 9 ]. Saha et al reported that gold nanoparticle reprograms pancreatic tumor microenvironment and inhibits tumor growth [ 10 ].…”

Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor

“…AuNPs can be stabilized by a large variety of stabilizers like polymers, ligands, biomolecules, denrimers, surfactants, etc. ; 84 , 101 , 102 , 103 , 104 the stabilizers affect not only the relative instability and aggregation but also cell uptake and toxicity, which points to the necessity of strategic engineering of NPs surface chemistry. 105 , 106 , 107 Gu and colleagues 108 developed a novel AuNP beacon by optimizing the sequence amount, and they modified PEG and cell-penetrating peptide (CPP) on the gold core ( Figure 5 ).…”