Electrostatic surface modifications to improve gene delivery

Abstract

Importance of the field: Gene therapy has the potential to treat a wide variety of diseases, including genetic diseases and cancer.

Areas covered in this review: This review introduces biomaterials used for gene delivery and then focuses on the use of electrostatic surface modifications to improve gene delivery materials. These modifications have been used to stabilize therapeutics in vivo, add cell-specific targeting ligands, and promote controlled release. Coatings of nanoparticles and microparticles as well as non-particulate surface coatings are covered in this review. Electrostatic principles are crucial for the development of multilayer delivery structures fabricated by the layer-by-layer method.

What the reader will gain: The reader will gain knowledge about the composition of biomaterials used for surface modifications and how these coatings and multilayers can be utilized to improve spatial control and efficiency of delivery. Examples are shown for the delivery of nucleic acids, including DNA and siRNA, to in vitro and in vivo systems.

Take home message: The versatile and powerful approach of electrostatic coatings and multilayers will lead to the development of enhanced gene therapies.

Figure 1

Biomaterials used to form particles and coatings for gene delivery.

Figure 2

Fabrication of a multilayer particle. Synthesis begins with a charged colloidal substrate. Oppositely charged polyelectrolytes are added in solution in a cyclic fashion. After the addition of each polyelectrolyte there is a wash and centrifugation step. As a final step, targeting ligands can be electrostatically added (yellow triangles). The colloidal substrate can be left encapsulated for delivery or can be chemically degraded and removed to form a hollow core.

Figure 3

SiRNA modified gold-nanoparticles (orange sphere) are electrostatically coated with cationic polymers (PBAEs) to enhance cell transfection. Reproduced with permission from Nano Letters. Copyright ACS 2009 [78].

Figure 4

Multilayered coatings can be added to structures such as glass slides, stents, and organic tissues. In each case, an oppositely charged polyelectrolyte is added to a charged surface followed by a wash step to remove excess polyelectrolyte. The next layer of oppositely charged polyelectrolytes can then be added and this cycle can be repeated as needed.

Figure 5

Fluorescence microscopy image showing localized transfection of COS-7 cells. The white lines show the approximate boundary between targeted and non-targeted delivery areas. The targeted areas are the quartz substrate functionalized with multilayered films of a PBAE polymer (seen in Figure 1) and pEGFP. Reproduced with permission from Journal of Controlled Release. Copyright Elsevier 2005 [105].

Figure 6

Cumulative transfection of NIH-3T3 (a) and SMC (b) cells with SEAP-DNA (secreted alkaline phosphatase based luminescence). Three surfaces were used: stainless steel mesh coated with DNA/reducible polymer multilayer (■), DNA/PEI multilayer (●), and control non-coated mesh (▲). Reproduced with permission from Biomaterials. Copyright Elsevier 2009 [107].