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Review
. 2016 May;241(10):1127-37.
doi: 10.1177/1535370216649445. Epub 2016 May 13.

Programmable biomaterials for dynamic and responsive drug delivery

Anna Stejskalová  1 , Mehrdad T Kiani  1 , Benjamin D Almquist  2
Affiliations
Review

Programmable biomaterials for dynamic and responsive drug delivery

Anna Stejskalová et al. Exp Biol Med (Maywood). 2016 May.

Abstract

Biomaterials are continually being designed that enable new methods for interacting dynamically with cell and tissues, in turn unlocking new capabilities in areas ranging from drug delivery to regenerative medicine. In this review, we explore some of the recent advances being made in regards to programming biomaterials for improved drug delivery, with a focus on cancer and infection. We begin by explaining several of the underlying concepts that are being used to design this new wave of drug delivery vehicles, followed by examining recent materials systems that are able to coordinate the temporal delivery of multiple therapeutics, dynamically respond to changing tissue environments, and reprogram their bioactivity over time.

Keywords: Bionanoscience; bacteria; biomaterials; cancer; drug delivery; nanoparticles.

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Figures

Figure 1
Figure 1
There are a variety of enabling technologies that underlie the ability to program functionality into therapeutic materials. (a) Click chemistry reactions are convenient for their high reaction efficiency, bio-orthogonality, specificity, and low toxicity. The stereotypical click reaction is the Cu-catalyzed alkyne-azide reaction, although the Cu catalyst can present toxicity problem in vivo. Other click reactions such as the one between an azide and dibenzocyclooctyne (DBCO) do not require Cu catalysts, instead being catalyzed by the ring strain present in the cyclooctyne. (b) Nucleic acids provide an additional avenue for programming functionality into materials. Aptamers can be used both for targeting over-expressed proteins on cell surfaces and as a therapeutic. (c) Finally, the breakdown and release of materials are tuneable by using enzyme degradable sequences, such as those that are substrates for MMPs. (A color version of this figure is available in the online journal.)
Figure 2
Figure 2
(a) Morton et al. have designed a liposome to target cancer cells and stagger the release of encapsulated therapeutics. In this case, folate conjugated to the surface of liposomes promoted enhanced binding to triple-negative breast cancer cells. Erlotinib loads into the core of the lipid bilayer due to its hydrophobic nature, while Dox loads into the aqueous vesicle core. (b) This arrangement of therapeutics allows for the initial release of erlotinib, followed by a slower release of Dox. Using this specific sequence of therapy results in the rewiring of cancer cells to make them more susceptible to DNA damage, dramatically increasing the efficacy of this combination of drugs. (A color version of this figure is available in the online journal.)
Figure 3
Figure 3
Nanoparticles have been developed that contain DNA antisense oligonucleotide hairpins conjugated to gold nanoparticles. 5-FU can then be loaded within the double helix of the hairpins. Following entry into cancer cells, the DNA hairpins hybridize with and silence the mRNA associated with 5-FU drug resistance while simultaneously releasing the bound 5-FU. This strategy has been shown to significantly increase effectiveness of 5-FU on 5-FU resistant cancer cells. (A color version of this figure is available in the online journal.)
Figure 4
Figure 4
Click chemistry has been used to concentrate systemic drugs at the site of interest,, which can be accomplished in several ways. (Top) Hydrogels functionalized with a molecule such as DBCO can be injected into a localized tissue site. Subsequent injection with azide-tagged therapeutics enables concentration at the hydrogel site via the click reaction. (Bottom) Cells can also be labeled with azide groups to directly target the cells themselves. Subsequent injection with therapeutics labeled with the complimentary click group, in this case DBCO, results in concentration at the membranes of the cells expressing azides followed by subsequent uptake. (A color version of this figure is available in the online journal.)
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