Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery

Abstract

Cationic enzymatically synthesized glycogen (cESG) is a naturally-derived, nano-scale carbohydrate dendrite that has shown promise as a cellular delivery vehicle owing to its flexibility in chemical modifications, biocompatibility and relative low cost. In the present work, cESG was modified and evaluated as a vehicle for tetraphenylporphinesulfonate (TPPS) in order to improve cellular delivery of this photosensitizer and investigate the feasibility of co-delivery with short interfering ribonucleic acid (siRNA). TPPS was electrostatically condensed with cESG, resulting in a sub-50 nm particle with a positive zeta potential of approximately 5 mV. When tested in normal ovarian surface epithelial and ovarian clear cell carcinoma cell culture models, encapsulation of TPPS in cESG significantly improved cell death in response to light treatment compared to free drug alone. Dosages as low as 0.16 μM TPPS resulted in cellular death upon illumination with a 4.8 J/cm2 light dosage, decreasing viability by 96%. cESG-TPPS was then further evaluated as a co-delivery system with siRNA for potential combination therapy, by charge-based condensation of an siRNA directed at reducing expression of manganese superoxide dismutase (Sod2) as a proof of principle target. Simultaneous delivery of TPPS and siRNA was achieved, reducing Sod2 protein expression to 48%, while maintaining the photodynamic properties of TPPS under light exposure and maintaining low dark toxicity. This study demonstrates the versatility of cESG as a platform for dual delivery of small molecules and oligonucleotides, and the potential for further development of this system in combination therapy applications.

Advanced dendritic glucan‐derived biomaterials: From molecular structure to versatile applications

“…Moreover, these Gly-siRNA nanoparticles are easily modifiable and relatively cost-effective to produce. They have also been shown to achieve protein knockdown and efficient photodynamic therapy (Engelberth et al, 2015(Engelberth et al, , 2017. Liang et al ( 2014) developed a series of hyperbranched cationic Gly derivatives conjugated with DMAPA and AEPZ residues, which exhibited higher gene-transfection efficiency, better blood compatibility, and lower cytotoxicity compared to branched polyethyleneimine (PEI) when utilized as a nonviral genedelivery vector for the inhibition of nuclear factor kappa B activation in human retinal pigment epithelial cells .…”

“…Dendritic glucans have also been used to encapsulate and release genetic material (Engelberth et al, 2015(Engelberth et al, , 2017Lan et al, 2020). Gly and amylopectin were functionalized by reacting with 1,2-ethylenediamine and diethylenetriamine to obtain different hyperbranched cationic polysaccharide derivatives (HCPs) (Figure 9B).…”

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

“…Another study applied lipopolysaccharide-amine nanopolymersomes loaded with specific siRNA (siNoggin), which enhanced the effect of bone differentiation in vitro [ 206 ]. The construction of cationic enzymatically synthesized glycogen (cESG) can achieve the simultaneous delivery of tetraphenylporphine sulfonate (TPPS) and siRNA, which can reduce the survival rate of cancer cells (ovarian clear cell cancer cells) [ 207 ]. In addition, cells transfected with the polysaccharide derivative DMAPA-Glyp/siRNA inhibited the activation of nuclear transcription factor-κB (NF-κB) in human retinal pigment epithelial (hRPE) cells, resulting in the expression of mRNA and protein being reduced, which can be used for gene therapy for diabetic retinopathy [ 208 ].…”

The Potential of Nanotechnology in Medically Assisted Reproduction

“…Magnetic nanoparticles ( Hua et al, 2017 ) have been used to treat cervical cancer in human cell cultures and xenograft mice. Other strategies include the delivering of siRNA in cationic dendritic starch ( Engelberth et al, 2017 ), layer-by-layer engineering of upconversion nanoparticles ( Lin et al, 2017 ), and mesoporous silica nanoparticles ( Roberts et al, 2017 ) resulting in improved cell death in human ovarian cancer cells.…”