Nanoassemblies with Effective Serum Tolerance Capability Achieving Robust Gene Silencing Efficacy for Breast Cancer Gene Therapy

Abstract

The transfection efficiency of siRNA mediated by cationic polymers is limited due to the instability of polymers/siRNA complexes in the presence of serum. Poly(ethylene glycol) (PEG) is usually applied to modify cationic polymers, so as to reduce protein and cell adsorption and then to improve siRNA transfection efficiency. However, the polymers’ modification with PEG mostly consumes the free amino of the polymers, which can, in turn, reduce the charge density and limit their siRNA transfection efficacy. Here, a new PEG modification strategy that need not consume the surface aminos of polymers is proposed. Catechol–PEG polymers are coated on the surface of phenylboronic acid (PBA)‐modified Generation 5 (G5) poly(amidoamine) dendrimers (G5PBA) via reversible boronate esters to establish PEG‐modified dendrimer/siRNA nanoassemblies for efficient siRNA delivery. The PEG/G5PBA/siRNA nanoassemblies have positive charge and show excellent gene silencing efficacy in the absence of serum in vitro. More importantly, the PEG/G5PBA/siRNA nanoassemblies also exhibit excellent serum resistance and gene silencing efficacy in serum‐containing medium. Furthermore, the effective antiserum and gene silencing efficacy elicited by these nanoassemblies lead to excellent antitumor effects in vivo. This proposed strategy constitutes an important approach to reach an excellent gene silencing efficacy in the presence of serum.

Injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

“…As is known, PAMAM dendrimers are excellent candidates for delivery drugs or genes due to good special three-dimensional structure, biocompatibility, multivalent surface, and internal cavities [ 52 ]. Moreover, G5 PAMAM as cationic dendrimers have been shown to mediate efficient cellular uptake and transfection of siRNA in multiple studies [ 53 ]. However, in consideration of possible cytotoxicity associated with dendrimers [ 54 ] and based on results of the gelation time, we used 1% (wt%) PAMAM in further investigations.…”

A siRNA-Assisted Assembly Strategy to Simultaneously Suppress “Self” and Upregulate “Eat-Me” Signals for Nanoenabled Chemo-Immunotherapy

“…In addition, the resultant VNP siCD47/MTO displayed good colloidal stability in a phosphate buffer solution (PBS), 10% serum, and 5% glucose (Figure 2F), which should be attributed to its PEG shell. 23,24 And, the encapsulated siRNA and MTO•2HCl could be efficiently released from the VNP siCD47/MTO (Figure S1). Interestingly, the release of MTO•2HCl was obviously faster than that of siRNA, which implied that both drugs were separate during the release process.…”

Harnessing reactive oxygen/nitrogen species and inflammation: Nanodrugs for liver injury

“…Positively charged polypeptides, cationic polymers and so on [ 276 , 277 ] have been developed as nanocarriers of siRNAs (polyanions), with the aim of reducing the TNF-α level at the site of liver injury. TNF-α is a critical pro-inflammatory factor and liver injury can be effectively alleviated through suppression of its expression in inflammatory cells.…”