Facing the Design Challenges of Particle-Based Nanosensors for Metabolite Quantification in Living Cells

Søndergaard, Rikke Vicki; Christensen, Niels Jørgen; Henriksen, Jonas Rosager; Kumar, E. K. Pramod; Almdal, Kristoffer; Andresen, Thomas Lars

doi:10.1021/cr400636x

Cited by 24 publications

(25 citation statements)

References 228 publications

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“…It is important to keep in mind that the nanosensor resides in the lysosomes, and that the reported pH measurements exclusively regard lysosomal pH irrespective of when the polyplexes may reach this compartment. Conclusively, we do not find that lipid conjugated PEI changes the pH in the lysosomal compartment, which is thereby similar to our previous study evaluating the proton sponge effect of conventional PEI [35].…”

Section: Lysosomal Phsupporting

confidence: 91%

“…Measurements of lysosomal pH were performed with a triple-labelled fluorescent nanosensor as described in our published protocol and review [34,35]. Briefly, HT1080 cells were plated in Ibidi 8-well µ-slides (27,000 cells/well in 300 µL/well) in complete medium and incubated overnight.…”

Section: Ratiometric Ph Measurements In the Lysosomal Compartmentmentioning

confidence: 99%

“…Furthermore, we have previously established that the nanosensor does not affect cell viability [34,35].…”

Section: Lysosomal Phmentioning

confidence: 99%

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Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

et al. 2016

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Future improvements of non-viral vectors for siRNA delivery require better understanding of intracellular processing and vector interactions with target cells. Here, we have compared the siRNA delivery properties of a lipid derivative of bPEI 1.8kDa (DOPE-PEI) with branched polyethyleneimine (bPEI) with average molecular weights of 1.8kDa (bPEI 1.8kDa) and 25 kDa (bPEI 25kDa). We find mechanistic differences between the DOPE-PEI conjugate and bPEI regarding siRNA condensation and intracellular processing. bPEI 1.8kDa and bPEI 25kDa have similar properties with respect to condensation capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8kDa improves the siRNA delivery properties, but with markedly different 2 formulation requirements and mechanisms of action compared to conventional PEIs. Interestingly, strong knockdown using bPEI 25kDa is dependent on the presence of a free vector fraction which does not increase siRNA uptake. Finally, we have investigated the effect on lysosomal pH induced by these vectors to elucidate the differences in the proton sponge effect between lipid conjugated PEI and conventional PEI: Neither DOPE-PEI nor bPEI 25kDa affected lysosomal pH as a function of time, underlining that the possible proton sponge effect is not associated with changes in lysosomal pH.

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Section: Lysosomal Phsupporting

confidence: 91%

Section: Ratiometric Ph Measurements In the Lysosomal Compartmentmentioning

confidence: 99%

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Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

et al. 2016

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“…High-performance, stimuli-responsive nanomaterials that can sharply respond to and amplify biological signals are rapidly developed for disease diagnosis and therapy1234567. Synthetic approaches employing traditional covalent bond chemistry may be limited in achieving highly complex nanostructures of over 10 6 Da in molecular weight.…”

mentioning

confidence: 99%

Molecular basis of cooperativity in pH-triggered supramolecular self-assembly

et al. 2016

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Supramolecular self-assembly offers a powerful strategy to produce high-performance, stimuli-responsive nanomaterials. However, lack of molecular understanding of stimulated responses frequently hampers our ability to rationally design nanomaterials with sharp responses. Here we elucidated the molecular pathway of pH-triggered supramolecular self-assembly of a series of ultra-pH sensitive (UPS) block copolymers. Hydrophobic micellization drove divergent proton distribution in either highly protonated unimer or neutral micelle states along the majority of the titration coordinate unlike conventional small molecular or polymeric bases. This all-or-nothing two-state solution is a hallmark of positive cooperativity. Integrated modelling and experimental validation yielded a Hill coefficient of 51 in pH cooperativity for a representative UPS block copolymer, by far the largest reported in the literature. These data suggest hydrophobic micellization and resulting positive cooperativity offer a versatile strategy to convert responsive nanomaterials into binary on/off switchable systems for chemical and biological sensing, as demonstrated in an additional anion sensing model.

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“…Despite widespread interest, molecular understanding of underlying supramolecular chemistry remains elusive. Part of the challenge is the lack of identification and evaluation of key structural and environmental parameters that affect their stimuli-response and accompanied supramolecular self-assembly, which hampers our capability in the rational design of responsive nanomaterials in a predictable fashion 11 .…”

Section: Introductionmentioning

confidence: 99%

Non-covalent interactions in controlling pH-responsive behaviors of self-assembled nanosystems

Wang

et al. 2016

Polym. Chem.

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Self-assembly and associated dynamic and reversible non-covalent interactions are the basis of protein biochemistry (e.g., protein folding) and development of sophisticated nanomaterial systems that can respond to and amplify biological signals. In this study, we report a systematic investigation of non-covalent interactions that affect the pH responsive behaviors and resulting supramolecular self-assembly of a series of ultra-pH sensitive (UPS) block copolymers. Increase of hydrophobic and π-π stacking interactions led to the decrease of pKa values. In contrast, enhancement of direct ionic binding between cationic ammonium groups and anionic counter ions gave rise to increased pKa. Moreover, hydration of hydrophobic surfaces and hydrogen bonding interactions may also play a role in the self-assembly process. The key parameters capable of controlling the subtle interplay of different non-covalent bonds in pH-triggered self-assembly of UPS copolymers are likely to offer molecular insights to understand other stimuli-responsive nanosystems. Selective and precise implementation of non-covalent interactions in stimuli-responsive self-assembly processes will provide powerful and versatile tools for the development of dynamic, complex nanostructures with predictable and tunable transitions.

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Facing the Design Challenges of Particle-Based Nanosensors for Metabolite Quantification in Living Cells

Cited by 24 publications

References 228 publications

Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

Molecular basis of cooperativity in pH-triggered supramolecular self-assembly

Non-covalent interactions in controlling pH-responsive behaviors of self-assembled nanosystems

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