Theranostic Layer‐by‐Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing

Boehnke, Natalie; Correa, Santiago; Hao, Liangliang; Wang, Wade; Straehla, Joelle P.; Bhatia, Sangeeta N.; Hammond, Paula T.

doi:10.1002/anie.201911762

Cited by 58 publications

(42 citation statements)

References 39 publications

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“…We generated a new class of targeted theranostic LbL nanoparticles consisting of a liposomal core, poly- l -arginine (PLR) and siRNA inner layers, and PLD as the tumor targeting surface coating. 52 We observed efficient tumor targeting not only in ovarian cancer mouse models but also in murine models of colorectal and pancreatic cancer. Taking further advantage of the unique trafficking features afforded by our newly discovered LbL NP surface chemistries, we recently employed PLE coatings to create a potent and safe cytokine delivery platform.…”

Section: Layer-by-layer Assembly: a Modular Approach To Biology-focused Nanocarrier Designmentioning

confidence: 83%

Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine

Boehnke

Hammond

2021

JACS Au

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Nanocarriers have significant potential to advance personalized medicine through targeted drug delivery. However, to date, efforts to improve nanoparticle accumulation at target disease sites have largely failed to translate clinically, stemming from an incomplete understanding of nano–bio interactions. While progress has been made to evaluate the effects of specific physical and chemical nanoparticle properties on trafficking and uptake, there is much to be gained from controlling these properties singularly and in combination to determine their interactions with different cell types. We and others have recently begun leveraging library-based nanoparticle screens to study structure–function relationships of lipid- and polymer-based drug delivery systems to guide nanoparticle design. These combinatorial screening efforts are showing promise in leading to the successful identification of critical characteristics that yield improved and specific accumulation at target sites. However, there is a crucial need to equally consider the influence of biological complexity on nanoparticle delivery, particularly in the context of clinical translation. For example, tissue and cellular heterogeneity presents an additional dimension to nanoparticle trafficking, uptake, and accumulation; applying imaging and screening tools as well as bioinformatics may further expand our understanding of how nanoparticles engage with cells and tissues. Given recent advances in the fields of omics and machine learning, there is substantial promise to revolutionize nanocarrier development through the use of integrated screens, harnessing the combinatorial parameter space afforded both by nanoparticle libraries and clinically annotated biological data sets in combination with high throughput in vivo studies.

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Section: Layer-by-layer Assembly: a Modular Approach To Biology-focused Nanocarrier Designmentioning

confidence: 83%

Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine

Boehnke

Hammond

2021

JACS Au

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“…[219] For example, positively charged poly-L-arginine (PLR) and negatively charged siRNA were sequentially adsorbed on an anionic liposome nanoparticle, and the outmost layer was coated with propargylmodified poly-L-aspartate (pPLD) (Figure 9C). [220] The anionic pPLD provides excellent colloidal stability against serum proteins, and enables the further conjugation with azide-functionalized species such as iRGD and PEG. The fabricated LBL nanoparticles allow efficient siRNA delivery.…”

Section: Lbl Nanocapsulesmentioning

confidence: 99%

Design of polymers for siRNA delivery: Recent progress and challenges

Wang

Song

et al. 2021

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RNA interference with the ability to specifically silence target genes has shown great potential to treat various diseases. The primary challenge for RNA interference is to effectively and selectively deliver genetic materials such as small interfering RNA (siRNA) to targeted tissues and cells in vivo. Numerous efforts have been made to overcome the extracellular and intracellular barriers during siRNA delivery. In this review, we focused on most recent advances in the design of functional polymers to achieve efficient siRNA delivery via addressing the various parameters, including siRNA binding, serum stability, specific targeting, tissue penetration, cellular internalization, endosomal escape, and intracellular siRNA release. The beneficial roles of assembled polymer nanostructures and polymerbased hybrid nanocomposites in siRNA delivery were also reviewed. Finally, the challenges and perspectives in the future development of polymer-based siRNA delivery systems will be discussed.

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“…Alongside the Langmuir–Blodgett layer [ 125 ] as well as self‐assembled monolayer deposition, [ 126 ] a layer‐by‐layer deposition at the surface hold promise for various biomedical and catalytic applications. [ 26,27,127–130 ] The layer‐by‐layer functionalization approach is well‐studied in the case of the flat surface and film‐based substrates. [ 125,126 ] Besides 2D multi‐layer formation, the layer‐by‐layer functionalization on the surface of freestanding nanoparticles is promising because of their 3D interfacial ability.…”

Section: Various Assemblies Driven By Electrostatic Interactionsmentioning

confidence: 99%

Hierarchical Assemblies of Polymer Particles through Tailored Interfaces and Controllable Interfacial Interactions

Visaveliya

Köhler

2020

Adv Funct Materials

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Hierarchical assembly architectures of functional polymer particles are promising because of their physicochemical and surface properties for multi‐labeling and sensing to catalysis and biomedical applications. While polymer nanoparticles’ interior is mainly made up of the cross‐linked network, their surface can be tailored with soft, flexible, and responsive molecules and macromolecules as potential support for the controlled particulate assemblies. Molecular surfactants and polyelectrolytes as interfacial agents improve the stability of the nanoparticles whereas swellable and soft shell‐like cross‐linked polymeric layer at the interface can significantly enhance the uptake of guest nano‐constituents during assemblies. Besides, layer‐by‐layer surface‐functionalization holds the ability to provide a high variability in assembly architectures of different interfacial properties. Considering these aspects, various assembly architectures of polymer nanoparticles of tunable size, shapes, morphology, and tailored interfaces together with controllable interfacial interactions are constructed here. The microfluidic‐mediated platform has been used for the synthesis of constituents polymer nanoparticles of various structural and interfacial properties, and their assemblies are conducted in batch or flow conditions. The assemblies presented in this progress report is divided into three main categories: cross‐linked polymeric network's fusion‐based self‐assembly, electrostatic‐driven assemblies, and assembly formed by encapsulating smaller nanoparticles into larger microparticles.

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Theranostic Layer‐by‐Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing

Cited by 58 publications

References 39 publications

Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine

Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine

Design of polymers for siRNA delivery: Recent progress and challenges

Hierarchical Assemblies of Polymer Particles through Tailored Interfaces and Controllable Interfacial Interactions

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