Layer‐by‐Layer‐Assembled Capsule Size Affects the Efficiency of Packaging and Delivery of Different Genetic Cargo

Abstract

The lack of an efficient and versatile intracellular nucleic acids delivery platform impedes the clinical implementation of gene therapy. Advances in layer‐by‐layer (LbL) technology have led to the production of LbL polymer capsules, a promising universal delivery tool. The biocompatibility, sufficient packaging capacity, safety, low cost, and high variability of structure and composition of the LbL capsules make it possible to meet the requirements for clinical‐grade nonviral gene transfer. Here, the possibility of polymeric LbL capsules of different sizes (micrometer and sub‐micrometer‐sized) to serve as universal nonviral carriers for messenger RNA (mRNA) and small interfering RNA (siRNA) is considered. In particular, the internalization of capsules into human mesenchymal stem cells (hMSCs, as an example of adult primary stem cells), capsule uptake, and intracellular delivery of mRNA and siRNA is studied. Importantly, the use of micrometer‐ or sub‐micrometer‐sized polymer capsules (MicCaps and SubCaps) allows the mRNA or siRNA to be packaged and transferred into hMSCs with high efficiency. While the uptake efficiency is comparable between MicCaps and SubCaps, the latter are significantly more efficient than MicCap when transferring siRNAs. These results demonstrate the potential of the LbL capsules as a universal gene delivery platform, which can be tuned according to the properties of genetic cargo.

N-[4-(N,N,N-Trimethylammonium)Benzyl]Chitosan Chloride as a Gene Carrier: The Influence of Polyplex Composition and Cell Type

“…PEI is considered as a “gold standard” DNA transfection reagent with well-characterized efficiency for both cell lines and primary mammal cells [ 36 , 37 ]. The potential of PARG for genetic material delivery was also described in the literature [ 38 ], and it was extensively used by our group for the synthesis of micro- and nanosized carriers [ 39 , 40 ]. The mass ratios of the control polyplexes were chosen based on previously published optimal conditions [ 38 , 41 ].…”

Weak Polyelectrolytes as Nanoarchitectonic Design Tools for Functional Materials: A Review of Recent Achievements

“…The corresponding colloidal systems benefited from the better control and fine tuning of intermolecular forces by pH modulation [ 125 ], ionic strength [ 126 ], and temperature [ 127 ]. Biosourced charged species such as dextran [ 128 ], CHI [ 129 ], bovine serum albumin [ 130 ], and DNA have also been used as functional units to encapsulate and deliver genetic cargo [ 128 ] and even co-deliver a drug [ 131 ].…”

Polyelectrolyte Multilayered Capsules as Biomedical Tools

“…Tarakanchikova et al [271] probed the efficiency of LbL capsules of dextran and poly-L-arginine, with sizes ranging from several nanometers to a few micrometers for the intracellular delivery of messenger RNA (mRNA) and small interfering RNA (siRNA). They found that this type of non-viral vector allows the packing, and subsequent transfection, of both types of genetic material into human mesenchymal stem cells (hMSCs).…”