Programmed hydrolysis of nanoassemblies by electrostatic interaction-mediated enzymatic-degradation

Samarajeewa, Sandani; Zentay, Ryan P.; Jhurry, Nema D.; Li, Ang; Seetho, Kellie; Zou, Jiong; Wooley, Karen L.

doi:10.1039/c3cc46013d

Cited by 21 publications

(30 citation statements)

References 30 publications

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“…For example, 2 PK had a 12-fold higher conversion in comparison to 2 PD ( Figure 3B). This stark difference resulting from preferential hydrolysis of nanostructures by oppositely charged enzymes has also been observed by Wooley et al 24 using polymeric micelles.…”

Section: Electrostatic Recruitment or Repulsion Of Mmp-9supporting

confidence: 73%

Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design

et al. 2019

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Over-expression and activation of matrix metalloproteinase-9 (MMP-9) is associated with multiple diseases, and can serve as a stimulus to activate nanomaterials for sensing and controlled release. In order to achieve autonomous therapeutics with improved space-time targeting capabilities, several features need to be considered beyond the introduction of an enzyme-cleavable linker into a nanostructure. We introduce guiding principles for a customizable platform using supramolecular peptide nanostructures with three modular components to achieve tunable kinetics and morphology changes upon MMP-9 exposure. This approach enables: (1) fine-tuning of kinetics through introduction of ordered/disordered structures, (2) a 12-fold variation in hydrolysis rates achieved by electrostatic (mis) matching of particle and enzyme charge, and (3) selection of enzymatic reaction products that are either cell-killing nanofibers or that disintegrate. These guiding principles, which can be rationalized and involve exchange of just a few amino acids, enable systematic customization of enzyme-responsive peptide nanostructures for general use in performance optimization of enzyme-responsive materials.

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Section: Electrostatic Recruitment or Repulsion Of Mmp-9supporting

confidence: 73%

Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design

et al. 2019

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“…In contrast, 7 days after dissolution, the peak at 8 mL was significantly diminished, indicating some remaining intact Dg-cSCK. However, multiple new, prominent peaks were observed between 10 and 20 mL, which is consistent with the observation lactic acid and different sized oligo(lactic acid) were released from the original Dg-cSCK as a result of ester bond degradation[47, 53]. Importantly, these degradative products could be detected with greater sensitivity than in previous studies of degradation performed on these Dg-cSCKs.…”

Section: Resultssupporting

confidence: 86%

In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging

et al. 2016

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Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(DL-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Čerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design.

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“…Even during the early stages of development, crosslinking of polymer chain segments composing the shell layer of polymer micelles was demonstrated as an approach for the construction of amphiphilic core–shell nanoparticles of various sizes, shapes, and compositions . Moreover, covalent stabilization through shell crosslinking offered the ability to manipulate the initial nanoparticles; degradation and extraction of the core material, for example, was used to produce nanocages …”

Section: Introductionmentioning

confidence: 99%

“…26,31,38,40,[43][44][45][46] Moreover, covalent stabilization through shell crosslinking offered the ability to manipulate the initial nanoparticles; degradation and extraction of the core material, for example, was used to produce nanocages. 32,36,40,[47][48][49][50][51] Rather than being limited to the thermodynamically favored morphology created initially from aqueous solution-state assembly, in which a hydrophobic core is surrounded by a crosslinked hydrophilic shell, the robust character and structural versatility of shell crosslinked knedel-like (SCK) polymer micelle nanoparticles raise several questions regarding their morphological flexibility. Unlike their supramolecular micellar precursors, which undergo morphological changes, including inversion, 52,53 under environmental variations, such as changes in pH, 17 ionic strength, 19 and solvent system, 18,54,55 SCKs are essentially single molecules of nanometer-scale dimensions.…”

mentioning

confidence: 99%

Investigation of segmental reorganization within amphiphilic block polymer nanoparticles derived from shell crosslinked micelle templates: Shell crosslinked knedel‐like inversion

Zhang

Wooley

2019

Journal of Polymer Science

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The construction of nanoscopic materials by synthetic methodologies that iterate covalent and supramolecular interactions has been developed over the past three decades as a powerful method to afford complex functional materials. Indeed, the present study was nearly lost in the archives of dissertation research completed in 2001, which revealed nanoscale conformational dynamics in the segmental reorganization, and partial inversion, of topologically shell crosslinked knedel‐like (SCK) nanoparticles. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 204–214

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Programmed hydrolysis of nanoassemblies by electrostatic interaction-mediated enzymatic-degradation

Abstract: Electrostatic interaction-mediated enzymatic-hydrolysis of poly(lactide)-containing nanoscale assemblies is described. At physiological pH, degradable core–shell morphologies with charged shells can readily attract or repel enzymes carrying opposite or similar charges, respectively.

Cited by 21 publications

References 30 publications

Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design

Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design

In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging

Investigation of segmental reorganization within amphiphilic block polymer nanoparticles derived from shell crosslinked micelle templates: Shell crosslinked knedel‐like inversion

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