Biocomputing nanoplatforms as therapeutics and diagnostics

Evans, Annicka C.; Thadani, Nicole N.; Suh, Junghae

doi:10.1016/j.jconrel.2016.01.045

Cited by 37 publications

(30 citation statements)

References 41 publications

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“…10 Several viral vectors, including retrovirus and measles virus, 11,12 have also been engineered to be protease-responsive. Thus, activation by an intrinsic biomolecular stimulus, 13 such as an extracellular protease, is proving to be a promising approach for targeted therapy. 14 …”

Section: Introductionmentioning

confidence: 99%

Role of Tetra Amino Acid Motif Properties on the Function of Protease-Activatable Viral Vectors

Robinson

Judd

et al. 2016

ACS Biomater. Sci. Eng.

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Protease-activatable viruses (PAV) based on adeno-associated virus have previously been generated for gene delivery to pathological sites characterized by elevated extracellular proteases. “Peptide locks”, composed of a tetra-aspartic acid motif flanked by protease cleavage sequences, were inserted into the virus capsid to inhibit virus-host cell receptor binding and transduction. In the presence of proteases, the peptide locks are cleaved off the capsid, restoring the virus’ ability to bind cells and deliver cargo. Although promising, questions remained regarding how the peptide locks prevented cell binding. In particular, it was unclear if the tetra-amino acid (4AA) motif blocks receptor binding via electrostatic repulsion or steric obstruction. To explore this question, we generated a panel of PAVs with lock designs incorporating altered 4AA motifs, each wielding various chemical properties (negative, positive, uncharged polar, and hydrophobic) and characterized the resultant PAV candidates. Notably, all mutants display reduced receptor binding and decreased transduction effciency in the absence of proteases, suggesting simple electrostatics between heparin and the D4 motif do not play an exclusive role in obstructing virus-receptor binding. Even small hydrophobic (A4) and uncharged polar (SGGS) motifs confer a reduction in heparin binding compared to the wild type. Furthermore, both uncharged polar N4 and Q4 mutants (comparable in size to the D4 and E4 motifs respectively, but lacking the negative charge) demonstrate partial ablation of heparin binding. Collectively, these results support a possible dual mechanism of PAV lock operation, where steric hindrance and electrostatics make nonredundant contributions to the disruption of virus-receptor interactions. Finally, because of high virus titer production and superior capsid stability, only the negatively charged 4AA motifs remain viable design choices for PAV construction. Future studies probing the structure–function relationship of PAVs will further expand its promise as a gene delivery vector able to target diseased tissues exhibiting elevated extracellular proteases.

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Section: Introductionmentioning

confidence: 99%

Role of Tetra Amino Acid Motif Properties on the Function of Protease-Activatable Viral Vectors

Robinson

Judd

et al. 2016

ACS Biomater. Sci. Eng.

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“…The responding nano-objects can be represented by nanoporous membranes with variable nanoporosity [136] and by nanoparticles with aggregation/disaggregation features [161] dependento nt he chemical signals produced by enzymatic reactions.N anoparticlea ssembly-disassembly can be triggered by chemical signals processed through biomolecular logic gates representing abiocomputingn anoplatform for therapeutics and diagnostics. [202] Biomolecular logic gates have been used to arrange dynamically gold nanoparticles on DNA origami. [203] Assembling of gold nanoparticles has been demonstrated by using ap H-responsive DNA nanomachine logically processingbiomolecular input signals.…”

Section: Atomicforce Microscopy (Afm) Transduction Of Chemical Outputmentioning

confidence: 99%

Enzyme‐Based Logic Gates and Networks with Output Signals Analyzed by Various Methods

Katz

2017

ChemPhysChem

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The paper overviews various methods that are used for the analysis of output signals generated by enzyme‐based logic systems. The considered methods include optical techniques (optical absorbance, fluorescence spectroscopy, surface plasmon resonance), electrochemical techniques (cyclic voltammetry, potentiometry, impedance spectroscopy, conductivity measurements, use of field effect transistor devices, pH measurements), and various mechanoelectronic methods (using atomic force microscope, quartz crystal microbalance). Although each of the methods is well known for various bioanalytical applications, their use in combination with the biomolecular logic systems is rather new and sometimes not trivial. Many of the discussed methods have been combined with the use of signal‐responsive materials to transduce and amplify biomolecular signals generated by the logic operations. Interfacing of biocomputing logic systems with electronics and “smart” signal‐responsive materials allows logic operations be extended to actuation functions; for example, stimulating molecular release and switchable features of bioelectronic devices, such as biofuel cells. The purpose of this review article is to emphasize the broad variability of the bioanalytical systems applied for signal transduction in biocomputing processes. All bioanalytical systems discussed in the article are exemplified with specific logic gates and multi‐gate networks realized with enzyme‐based biocatalytic cascades.

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“…Nowadays, logic gate nanoplatforms exhibit great potential in nanomedicine . It is well established that logic gate DDSs can respond to multiple stimuli in tumor tissue/cells, realizing tumor specific drug delivery and release.…”

Section: Introductionmentioning

confidence: 99%

A Chimeric Peptide Logic Gate for Orthogonal Stimuli‐Triggered Precise Tumor Therapy

Dai

Han

2018

Adv Funct Materials

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The precise recognition of tumor tissue is the key challenge that hinders successful clinical translation of drug delivery systems. Herein, a tumor extracellular matrix orthogonal stimuli-responsive chimeric peptide is developed for logic gate controlled tumor recognition and photodynamic therapy. In vitro studies show that the negatively charged chimeric peptide is sensitive to two typical tumor hallmarks, i.e., mild acidity and matrix metalloproteinase 2 (MMP-2) simultaneously. Consequently, the chimeric peptide can undergo charge reversal from negative charge to positive charge in tumor, accelerating the cellular uptake. Specifically, the enhanced cellular uptake of chimeric peptide can be activated efficiently only in the presence of both acidity and MMP-2, endowing chimeric peptide with highly specific tumor therapy both in vitro and in vivo. This chimeric peptide based "AND" logic gate should show great potential in precise tumor therapy.

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Biocomputing nanoplatforms as therapeutics and diagnostics

Cited by 37 publications

References 41 publications

Role of Tetra Amino Acid Motif Properties on the Function of Protease-Activatable Viral Vectors

Role of Tetra Amino Acid Motif Properties on the Function of Protease-Activatable Viral Vectors

Enzyme‐Based Logic Gates and Networks with Output Signals Analyzed by Various Methods

A Chimeric Peptide Logic Gate for Orthogonal Stimuli‐Triggered Precise Tumor Therapy

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