The biodistribution of maltotriose modified poly(propylene imine) (PPI) dendrimers conjugated with fluorescein—proofs of crossing blood–brain–barrier

Janaszewska, Anna; Ziemba, Barbara; Ciepluch, Karol; Appelhans, Dietmar; Voit, Brigitte; Klajnert, Barbara; Bryszewska, Maria

doi:10.1039/c1nj20444k

Cited by 51 publications

(39 citation statements)

References 28 publications

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“…For the successful use of sugar-decorated poly(propylene imine) (PPI) dendrimers as a DDS [10][11][12] and a biological [13][14][15] and stabilizing [16] agent in (bio-)medical applications, one has to not only search for those potential application fields but also understand the cellular uptake and cellular trafficking in various cells. Moreover, a fundamental understanding of their molecular interaction properties against a biological cell membrane and model lipid membranes is mostly unknown.…”

Section: Introductionmentioning

confidence: 99%

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

Wrobel

Appelhans

Signorelli

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The influence of maltose-modified poly(propylene imine) (PPI) dendrimers on dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) (3%) liposomes was studied. Fourth generation (G4) PPI dendrimers with primary amino surface groups were partially (open shell glycodendrimers - OS) or completely (dense shell glycodendrimers - DS) modified with maltose residues. As a model membrane, two types of 100nm diameter liposomes were used to observe differences in the interactions between neutral DMPC and negatively charged DMPC/DMPG bilayers. Interactions were studied using fluorescence spectroscopy to evaluate the membrane fluidity of both the hydrophobic and hydrophilic parts of the lipid bilayer and using differential scanning calorimetry to investigate thermodynamic parameter changes. Pulsed-filed gradient NMR experiments were carried out to evaluate common diffusion coefficient of DMPG and DS PPI in D2O when using below critical micelle concentration of DMPG. Both OS and DS PPI G4 dendrimers show interactions with liposomes. Neutral DS dendrimers exhibit stronger changes in membrane fluidity compared to OS dendrimers. The bilayer structure seems more rigid in the case of anionic DMPC/DMPG liposomes in comparison to pure and neutral DMPC liposomes. Generally, interactions of dendrimers with anionic DMPC/DMPG and neutral DMPC liposomes were at the same level. Higher concentrations of positively charged OS dendrimers induced the aggregation process with negatively charged liposomes. For all types of experiments, the presence of NaCl decreased the strength of the interactions between glycodendrimers and liposomes. Based on NMR diffusion experiments we suggest that apart from electrostatic interactions for OS PPI hydrogen bonds play a major role in maltose-modified PPI dendrimer interactions with anionic and neutral model membranes where a contact surface is needed for undergoing multiple H-bond interactions between maltose shell of glycodendrimers and surface membrane of liposome.

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Section: Introductionmentioning

confidence: 99%

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

Wrobel

Appelhans

Signorelli

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…29 In our recent work we have demonstrated that anti-prion activity is not limited to cationic dendrimers and that a high density of reactive surface groups is a necessity. Furthermore we showed for the first time that a dendrimer is capable of inhibiting the intracellular conversion of PrP C to PrP Sc .…”

Section: Disclosure Of Potential Conflicts Of Interestmentioning

confidence: 99%

“…This is another modified version of the sSCA and specifically detects FL PrP Sc -it does not detect PrP C or PrP. [27][28][29][30] Two drugs with a known method of action, suramin and STI571, were used to validate the assay and demonstrate that our system is capable of determining an anti-prion therapeutics' mode of action. Finally, the system was used to examine how mPPIg5 eliminates PrP Sc from cells.…”

Section: Properties Which Govern Anti-prion Activity Of Dendrimersmentioning

confidence: 99%

“…15 The truncated PrP Sc formed by this event is known as PrP [27][28][29][30] and accumulates in lysosomes. 15 For the sake of clarity, we use the term "full length PrP Sc (FL PrP Sc )" to refer to non-truncated protease resistant PrP Sc and PrP [27][28][29][30] to refer to truncated protease resistant PrP Sc . PrP Sc is used to refer to all disease isoforms of the prion protein.…”

Section: Exploiting the Intracellular Cleavage Of Prp Scmentioning

confidence: 99%

“…In summary: PrP C → FL PrP Sc → PrP. [27][28][29][30] As FL PrP Sc is short lived, its intracellular level is closely related to its production rate. If the synthesis of FL PrP Sc is interfered with, the level of detectable eliminates PrP Sc with minimum toxicity to the cell and with no detectable effect on endogenous PrP C is, from a theoretical viewpoint at least, ideal.…”

Section: Exploiting the Intracellular Cleavage Of Prp Scmentioning

confidence: 99%

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Tatzelt

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Dendrimers as Powerful Building Blocks in Central Nervous System Disease: Headed for Successful Nanomedicine

Leiro

Santos

Lopes

et al. 2017

Adv Funct Materials

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Dendrimers have emerged as a powerful class of nanomaterials in the nanomedicine field due to their unique structural features: globular, welldefined, highly branched and controllable structure, nanosizescale, low polydispersity, and the presence of several terminal groups that can be functionalized with different ligands simulating the multivalency present in different biological systems. Although in its infancy, the application of dendrimers as therapeutics or theranostic tools in central nervous system (CNS) disorders is already significant and has opened promising avenues in the treatment of many conditions where the inherent "smartness" of the dendritic structures is being explored to effectively target the CNS. Here we present an overview of the past and future challenges of the use of dendrimers to respond to one of the ultimate challenges in the (nano)medicine field: to attain CNS repair and regeneration.

show abstract

The biodistribution of maltotriose modified poly(propylene imine) (PPI) dendrimers conjugated with fluorescein—proofs of crossing blood–brain–barrier

Cited by 51 publications

References 28 publications

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

Nanomedicine for prion disease treatment

Dendrimers as Powerful Building Blocks in Central Nervous System Disease: Headed for Successful Nanomedicine

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