Engineering CNDP’s of dendrimers containing phosphorous interior compositions to produce new emerging properties
Phosphorus-containing dendrimers are defined as dendrimers having at least one phosphorus atom at each branching point. In this review, we will show how phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, to afford specific properties, such as fluorescence to image biological events. Accelerated methods of synthesis of phosphorus (one step for one generation) will be also displayed, as well as the specific reactivity of P=N–P=S linkages obtained in most of these accelerated method of synthesis, which has led to particularly original dendritic architectures, such as dendrons included in dendrimers. Finally, we will display how modifications of the internal structure of a series of dendrimers having the same type and number of terminal functions can deeply modify their biological anti-inflammatory properties. Among the six critical nanoscale design parameters (CNDP), we will show how two of them, i.e., architecture and elemental composition, have been particularly engineered to modify phosphorus-containing dendrimers, in order to fulfill the desired properties.
KeywordsPhosphorus chemistry Monomers Dendrimers Fluorescence CNDP Nanoscale architectures
In this review, we will consider in particular how the two last parameters (architecture and elemental composition) may influence the properties of phosphorus-containing dendrimers, which are defined as dendrimers having at least one phosphorus atom at each branching points. We will show first how the synthesis of phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, in particular not only to incorporate linkages that are able to be modified after the synthesis of the dendrimers, leading to unprecedented architectures, but also to improve the synthesis by decreasing the number of steps for a given number of terminal functions. We will show also how the modifications of the internal structure may deeply modify the biological properties, even with identical terminal functions.
Synthesis of phosphorhydrazone dendrimers
This method of synthesis is compatible with numerous types of modifications of the internal structure, in particular by replacing 4-hydroxybenzaldehyde by other hydroxyl aldehydes, even hydroxyl dialdehydes, and other types of dialdehydes. We will display in the next paragraphs how these modifications influence the properties of these dendrimers.
Internal functionalization of phosphorhydrazone dendrimers, and influence on the properties
Electrochemical properties of phosphorus dendrimers with ferrocenes in the internal structure
We have also studied the chiroptical properties of all the dendrimers of type Fe x @G n in which the chirality of the ferrocene is afforded by the presence of two substituents on the same cyclopentadiene (planar chirality). We have measured the optical rotation for all three families of dendrimers. The values of [αD] (specific rotation) depend almost exclusively on the chemical environment of the chiral ferrocenes, and not on the generation considered. Indeed, a dramatic change in [αD] is observed on going from the aldehyde to the hydrazone substituents of the ferrocenes. The molar rotation values [αmol] divided by the number of chiral entities are a constant for all series having the same chemical environment, for instance Fe 24 @G 3 , Fe 96 @G 5 , and Fe 1536 @G 9 (or Fe 24 @G 5 , Fe 96 @G 7 , and Fe 1536 @G 11 ). On the contrary, [αmol] divided by the number of chiral entities is very sensitive to changes in the chemical environment, from Fe x @G n to Fe x @G n + 1 (aldehyde → hydrazone) (Fig. 4d) (Turrin et al. 2002b).
Fluorophores in the internal structure of phosphorhydrazone dendrimers, and their use in biology
Different types of fluorophores have been incorporated inside phosphorhydrazone dendrimers, either at the core, or linked to the core (off-center), or as constituents of the branches, by replacing 4-hydroxybenzaldehyde, as already shown above in the case of ferrocenes. In most cases, the terminal functions are modified to ensure the solubility in water, in view of biological experiments (Caminade et al. 2009).
Fluorophores used as core of phosphorhydrazone dendrimers
The two-photon (2P) excited fluorescence is based on the simultaneous absorption of two photons instead of one photon in standard excitation, to reach the excited state of the fluorophore, subsequently leading to fluorescence emission. A focussed fluorescence and a deeper penetration in biological tissues are observed with this method; thus, it is particularly interesting for in vivo imaging. Specially engineered fluorophores having two-photon absorption properties (Fig. 6b, c) were linked to two triphosphazene rings as core of phosphorhydrazone dendrimers. The second generation of the dendrimer having the fluorophore shown in Fig. 6b as core and ended by ammonium groups has been used for imaging in vivo the vascular network of a rat olfactory bulb (Krishna et al. 2006). The same core was used to build dendrimers having another two-photon fluorophore as terminal functions, and to study the interactions between the core and the surface, depending on the generation (G0–G2) (Mongin et al. 2007). With a longer core (Fig. 6c), and ammonium water-solubilizing terminal functions, the phosphorhydrazone dendrimer was used for studying its fluorescence, depending on the solvent (Rouxel et al. 2012), and for imaging in vivo the vascular network of a tadpole (Mongin et al. 2008).
Fluorophores used as branches of phosphorhydrazone dendrimers
A related hydroxyl aldehyde is the azobenzene derivative shown in Fig. 7c. This azobenzene was incorporated either at the level of the first generation, and the dendrimer was built up to the third generation, or at all layers, also up to the third generation. The fluorescence properties of these compounds were not studied, but the photo-induced trans → cis isomerization of the azo groups and their thermal cis → trans isomerization in the dark were studied, mainly by NMR (Deloncle et al. 2008). The relative amount of cis and trans isomers obtained at the photostationary equilibrium differs largely, depending on the location of the azobenzene groups: The more the azobenzene groups are buried inside the dendrimer, the more they are reluctant to isomerize (Sebastian et al. 2002).
Fluorophores linked “off-center” to the core
Other examples of off-center dendrimers, and their use for grafting to materials
Accelerated methods of synthesis of phosphorus dendrimers
The method of synthesis shown in Fig. 2 was also used in all the other cases shown in the previous paragraphs. This method is very robust and powerful, but it is a lengthy process, which necessitates two steps for each generation. Thus, it is important to try to shorten the synthetic process, in particular by obtaining a new generation at each step, and not every two steps. In these cases, layered dendrimers are obtained, in which the types of terminal groups are identical every two generations, and not every generation. These methods can be viewed also as a way to multiply more rapidly the number of terminal functions.
Phenol dialdehydes for accelerated syntheses of phosphorhydrazone dendrimers
Other accelerated methods of synthesis, based on P=N–P=S linkages
In all these cases, there are phosphines as terminal functions at some steps, which can be very useful for complexing diverse metals (Caminade et al. 1998) and for catalysis (Caminade et al. 2008, 2016b). There are also P=N–P=S linkages everywhere in the internal structure, which have a versatile reactivity that will be displayed in the forthcoming paragraphs.
P=N–P=S linkages at the core of dendrons for the synthesis of special dendritic architectures
Reactivity of the internal P=N–P=S linkages: towards dendrons inside dendrimers
The electronic delocalization all along the P=N–P=S linkages induces a mesomeric form with a negative charge on sulfur and a positive charge on phosphorus (+P–N=P–S−). It means that the sulfur atom can potentially react with electron-deficient entities (metallic derivatives or organic electrophiles). To observe more easily the reactivity of the P=N–P=S linkages, we have generally introduced them at a single layer inside the dendrimers, and not at several or all layers as shown in Figs. 11 and 12, using the method of synthesis shown in Fig. 2 for the layers not including such linkages.
Specific alkylation or complexation on the sulfur atom of the P=N–P=S linkages
The alkylation of sulfur induces a weakening of the strength of the PS bond, which can be easily cleaved using a nucleophilic phosphine such as P(NMe2)3, to generate tricoordinated phosphorus atoms inside the structure (Fig. 15b, c). The PIII inside the structure can be alkylated using alkyliodides, such as methyliodide and allyliodide (Fig. 15c), but can react also with diverse azides in Staudinger reactions (Fig. 15b, c). The reaction with N3-P(S)(OC6H4-CHO)2 (called monomer CD 2 in Fig. 11) is particularly interesting, as will be seen in the forthcoming paragraphs (Fig. 15c) (Larre et al. 1998a). All the process is also compatible with the presence of aldehyde terminal functions (Fig. 15d). It has been used in particular for the grafting of fluorescent pyrene groups inside the dendrimers, using the Staudinger reaction in the last step. These fluorescent functions revealed that the internal structure contains many molecules of solvents, as the movement of the internal pyrene groups was analogous to the movement of pyrenes in a small model compound. Indeed, the ratio of the intensity of pyrene-pyrene excimer and of pyrene depended only on the solvent used and not on the size of the molecules tested (monomer or dendrimer) (Fig. 15d) (Brauge et al. 2001a).
Reactivity of aldehyde internal functions
Introducing new branches inside the structure of dendrimers
Viologen-containing phosphorus dendrimers
Different types of biological experiments were carried out with these new viologen derivatives. The main conclusion was that the biological behavior strongly depends on the size, molecular weight, number of viologen units, and nature of the terminal functions, as an illustration of the CNDP concept. In a first paper, hemolysis, cytotoxicity, antibacterial, and antifungal activity induced by these phosphorus-viologen dendrimers were investigated. The most hemolytic dendrimers, measured on red blood cells obtained from healthy donors, were those of first generations, whereas generation 0 ended by PEG (polyethyleneglycol) was the least hemolytic. The cytotoxicity, measured with B14 Chinese hamster peritoneal fibroblasts, indicated also that the least toxic was the generation 0 ended by PEGs. Interestingly, cytotoxicity measured with N2a mouse neuroblastoma cell lines showed that this PEG dendrimer was the most toxic. A dendrimer which is harmless to normal cells but highly toxic to cancer cells is particularly interesting. The anti-microbial activity was tested on a Gram-positive bacterium, three Gram-negative bacteria, and yeast. In general, the dendrimers having the largest number of viologen units have the highest anti-microbial activity, whereas the PEG dendrimer has no activity (Ciepluch et al. 2012a). The influence of viologen-based dendrimers on human serum albumin (HSA), which is the most abundant protein in plasma, has been also investigated. All viologen dendrimers decreased significantly the HSA fluorescence intensity, but they do not modify the circular dichroism (CD) spectra of albumin, except for those having aldehyde terminal functions (Ciepluch et al. 2012b). The cytotoxicity and the interaction with HSA were also studied with the mixed phosphorus-viologen-carbosilane dendrimers, but it was shown that in this case, the properties mainly depended on the ammonium surface groups, and not on the internal structure (Moreno et al. 2015). The interaction of these mixed dendrimers with several proteins (alkaline phosphatase from E. coli, human aspartate transaminase and l-lactate dehydrogenase from rabbit muscles) was also studied (Szwed et al. 2016).
Several experiments were carried out with the viologen dendrimers in the context of neurodegenerative diseases. The toxicity of the generation 0 viologen dendrimers having phosphonate terminal functions, built from either the trifunctional or the hexafunctional core, was tested towards embryonic mouse hippocampal cells (cells from the central nervous system). The cytotoxicity of these dendrimers was low in both cases, and they declined the level of reactive oxygen species (ROS), due to their ability to quench ROS (Lazniewska et al. 2013). Furthermore, these dendrimers can prevent damages induced by rotenone (a pesticide) on these cells (Milowska et al. 2014). The inhibition by several viologen dendrimers of acetylcholinesterase and butyrylcholinesterase activity, two enzymes that are deeply implicated in neurodegenerative diseases, was also demonstrated (Ciepluch et al. 2013). The inhibition of α-synuclein fibril formation by the same series of viologen dendrimers was more pronounced when using the phosphonate derivative, compared to the PEG derivative, showing a potential therapeutic strategy in Parkinson’s disease and in other synucleinopathies (Milowska et al. 2013).
Influence of internal modifications on the biological properties of dendrimers
In view of all these important properties, a large screening to determine the structure/activity relationship was carried out. In first attempts, the nature of the terminal functions (Griffe et al. 2007), the generation, and the number of terminal functions (Rolland et al. 2008) were studied. It was deduced from these experiments that 8 to 12 symmetrical azabisphosphonate linkages are necessary to observe the biological properties. Thus, in a next step of structural modifications, we decided to modify the internal structure of dendrimers, while keeping the same type and number of azabisphosphonate groups on the surface. For this purpose, we synthesized other types of phosphorhydrazone dendrimers, one with longer internal branches (Fig. 19b), and one with longer linker to the azabisphosphonates (Fig. 19c). We also synthesized other “inorganic” dendrimers, one based on thiophosphate linkages (Fig. 19d) (Salamonczyk et al. 2000), and one based on carbosilane branches (Fig. 19e) (Zhou and Roovers 1993), both having also azabisphosphonate terminal groups. Finally, we synthesized “organic” dendrimers, based on nitrogen at the branching points, of types PAMAM (Fig. 19f) (Tomalia et al. 1985), PPI (Fig. 19g) (de Brabander van den Berg and Meijer 1993), and poly(l-lysine) (Fig. 19h) (Aharoni et al. 1982), all of them having azabisphosphonate terminal groups. The ability of all these families of dendrimers to activate monocytes was checked. To our surprise, despite the presence of the same type of terminal functions and of an analogous number of these terminal functions, all the dendrimers with nitrogen at the branching points (Fig. 19f–h) have absolutely no activity, whereas all the others are active, the most active being still the first dendrimer synthesized, shown in Fig. 19a. To try to understand this astonishing result, theoretical studies by molecular modeling were carried out with all the dendrimers shown in Fig. 19, in explicit water. These studies showed that these very different dendrimers can be separated into two families: those having a directional structure in water, with all the terminal functions gathered on the same side, which were active, and those having the terminal functions spread all over the surface, which were non-active. This was the very first example of the influence of the internal structure of dendrimers on their properties, carried out with a large number of families of dendrimers (Caminade et al. 2015).
In this review, we have shown how modifications of the internal structure of phosphorhydrazone dendrimers, at the level of the architecture and of the chemical composition, can deeply modify the properties of dendrimers. Phosphorus-containing dendrimers are certainly one of the most versatile class of dendrimers, due to the large number of modifications offered by phosphorus chemistry. Among the examples given, one can cite the incorporation of ferrocenes inside the structure, to modify the electrochemical properties, leading to the very first example of a switch ON-OFF dendritic catalyst, and the incorporation of fluorescent entities at different level, for imaging biological events at the cellular level, or imaging blood vessels of living animals. Incorporation of charges inside the structure (in particular viologen units) for studying their biological properties has been also shown. Different methods for accelerating the synthesis of dendrimers have been displayed (only one reaction per generation), affording layered dendrimers. Of interest are those incorporating P=N–P=S linkages in their structure, which display an original reactivity on the sulfur atom, which has led to the synthesis of particularly original dendritic architectures. Finally, the comparison of the anti-inflammation properties of a series of dendrimers having the same type and number of terminal functions, but a different internal architecture and chemical composition, has demonstrated the dramatic influence of these parameters on the biological properties. Undoubtedly, the CNDPs are of paramount importance for defining and classifying the different types of dendrimers and dendritic structures.
Thanks are due to the CNRS (Centre National de la Recherche Scientifique) for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Ciepluch K, Katir N, El Kadib A, Weber M, Caminade AM, Bousmina M, Majoral JP, Bryszewska M (2012b) Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin. J Lumin 132(6):1553–1563. https://doi.org/10.1016/j.jlumin.2012.01.044 CrossRefGoogle Scholar
- Ciepluch K, Weber M, Katir N, Caminade AM, El Kadib A, Klajnert B, Majoral JP, Bryszewska M (2013) Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities. Int J Biol Macromol 54:119–124. https://doi.org/10.1016/j.ijbiomac.2012.12.002 CrossRefGoogle Scholar
- de Jong ER, Deloch N, Knoll W, Turrin CO, Majoral JP, Caminade AM, Koper I (2015) Synthesis and characterization of bifunctional dendrimers: preliminary use for the coating of gold surfaces and the proliferation of human osteoblasts (HOB). New J Chem 39:7194–7205. https://doi.org/10.1039/c5nj00620a CrossRefGoogle Scholar
- Dib H, Rebout C, Laurent R, Mallet-Ladeira S, Sournia-Saquet A, Sarosi MB, Hey-Hawkins E, Majoral JP, Delavaux-Nicot B, Caminade AM (2016) Ordered layered dendrimers constructed from two known dendrimer families: inheritance and emergence of properties. Chem Eur J 22:10736–10742. https://doi.org/10.1002/chem.201601354 CrossRefGoogle Scholar
- El Brahmi N, El Kazzouli S, Mignani SM, Essassi E, Aubert G, Laurent R, Caminade AM, Bousmina MM, Cresteil T, Majoral JP (2013) Original multivalent copper(II)-conjugated phosphorus dendrimers and corresponding mononuclear copper(II) complexes with antitumoral activities. Mol Pharm 10:1459–1464. https://doi.org/10.1021/mp4000184 CrossRefGoogle Scholar
- Fruchon S, Mouriot S, Thiollier T, Grandin C, Caminade AM, Turrin CO, Contamin H, Poupot R (2015) Repeated intravenous injections in non-human primates demonstrate preclinical safety of an anti-inflammatory phosphorus-based dendrimer. Nanotoxicology 9:433–441. https://doi.org/10.3109/17435390.2014.940406 CrossRefGoogle Scholar
- Furer VL, Vandyukov AE, Majoral JP, Caminade AM, Gottis S, Laurent R, Kovalenko VI (2015b) Comparative DFT study of structure, reactivity and IR spectra of phosphorus-containing dendrons with P=N-P=S linkages, vinyl and azide functional groups. J Mol Struct 1091:6–15. https://doi.org/10.1016/j.molstruc.2015.02.067 CrossRefGoogle Scholar
- Griffe L, Poupot M, Marchand P, Maraval A, Turrin CO, Rolland O, Metivier P, Bacquet G, Fournie JJ, Caminade AM, Poupot R, Majoral JP (2007) Multiplication of human natural killer cells by nanosized phosphonate-capped dendrimers. Angew Chem Int Ed 46:2523–2526. https://doi.org/10.1002/anie.200604651 CrossRefGoogle Scholar
- Hayder M, Poupot M, Baron M, Nigon D, Turrin CO, Caminade AM, Majoral JP, Eisenberg RA, Fournie JJ, Cantagrel A, Poupot R, Davignon JL (2011) A phosphorus-based dendrimer targets inflammation and osteoclastogenesis in experimental arthritis. Science Transl Med 3:11. https://doi.org/10.1126/scitranslmed.3002212 CrossRefGoogle Scholar
- Ielasi F, Ledall J, Anes AP, Fruchon S, Caminade AM, Poupot R, Turrin CO, Blanzat M (2016) Influence of PPH dendrimers’ surface functions on the activation of human monocytes: a study of their interactions with pure lipid model systems. Phys Chem Chem Phys 18:21871–21880. https://doi.org/10.1039/c6cp03536a CrossRefGoogle Scholar
- Kazmierczak-Baranska J, Pietkiewicz A, Janicka M, Wei YQ, Turrin CO, Majoral JP, Nawrot B, Caminade AM (2010) Synthesis of a fluorescent cationic phosphorus dendrimer and preliminary biological studies of its interaction with DNA. Nucleosides Nucleotides Nucleic Acids 29:155–167. https://doi.org/10.1080/15257771003708462 CrossRefGoogle Scholar
- Keller M, Colliere V, Reiser O, Caminade AM, Majoral JP, Ouali A (2013) Pyrene-tagged dendritic catalysts noncovalently grafted onto magnetic co/C nanoparticles: an efficient and recyclable system for drug synthesis. Angew Chem Int Ed 52:3626–3629. https://doi.org/10.1002/anie.201209969 CrossRefGoogle Scholar
- Larre C, Donnadieu B, Caminade AM, Majoral JP (1998c) Regioselective gold complexation within the cascade structure of phosphorus-containing dendrimers. Chem Eur J 4:2031–2036. https://doi.org/10.1002/(sici)1521-3765(19981002)4:10<2031::aid-chem2031>3.0.co;2-j CrossRefGoogle Scholar
- Lazniewska J, Janaszewska A, Milowska K, Caminade AM, Mignani S, Katir N, El Kadib A, Bryszewska M, Majoral JP, Gabryelak T, Klajnert-Maculewicz B (2013) Promising low-toxicity of viologen-phosphorus dendrimers against embryonic mouse hippocampal cells. Molecules 18(10):12222–12240. https://doi.org/10.3390/molecules181012222 CrossRefGoogle Scholar
- Leclaire J, Dagiral R, Fery-Forgues S, Coppel Y, Donnadieu B, Caminade AM, Majoral JP (2005) Octasubstituted metal-free phthalocyanine as core of phosphorus dendrimers: a probe for the properties of the internal structure. J Am Chem Soc 127:15762–15770. https://doi.org/10.1021/ja054797b CrossRefGoogle Scholar
- Maraval V, Laurent R, Donnadieu B, Mauzac M, Caminade AM, Majoral JP (2000a) Rapid synthesis of phosphorus-containing dendrimers with controlled molecular architectures: first example of surface-block, layer-block, and segment-block dendrimers issued from the same dendron. J Am Chem Soc 122(11):2499–2511. https://doi.org/10.1021/ja992099j CrossRefGoogle Scholar
- Maraval V, Laurent R, Merino S, Caminade AM, Majoral JP (2000b) Michael-type addition of amines to the vinyl core of dendrons—application to the synthesis of multidendritic systems. Eur J Org Chem 3555–3568. doi: https://doi.org/10.1002/1099-0690(200011)2000:21<3555::AID-EJOC3555>3.0.CO;2-V
- Marmillon C, Gauffre F, Gulik-Krzywicki T, Loup C, Caminade AM, Majoral JP, Vors JP, Rump E (2001) Organophosphorus dendrimers as new gelators for hydrogels. Angew Chem Int Ed 40(14):2626–2629. https://doi.org/10.1002/1521-3773(20010716)40:14<2626::aid-anie2626>3.0.co;2-f CrossRefGoogle Scholar
- Maszewska M, Leclaire J, Cieslak M, Nawrot B, Okruszek A, Caminade AM, Majoral JP (2003) Water-soluble polycationic dendrimers with a phosphoramidothioate backbone: preliminary studies of cytotoxicity and oligonucleotide/plasmid delivery in human cell culture. Oligonucleotides 13:193–205. https://doi.org/10.1089/154545703322460586 CrossRefGoogle Scholar
- Merino S, Brauge L, Caminade AM, Majoral JP, Taton D, Gnanou Y (2001) Synthesis and characterization of linear, hyperbranched, and dendrimer-like polymers constituted of the same repeating unit. Chem Eur J 7:3095–3105. https://doi.org/10.1002/1521-3765(20010716)7:14<3095::aid-chem3095>3.0.co;2-s CrossRefGoogle Scholar
- Mignani S, El Brahmi N, Eloy L, Poupon J, Nicolas V, Steinmetz A, El Kazzouli S, Bousmina MM, Blanchard-Desce M, Caminade AM, Majoral JP, Cresteil T (2017) Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators. Eur J Med Chem 132:142–156. https://doi.org/10.1016/j.ejmech.2017.03.035 CrossRefGoogle Scholar
- Mongin O, Rouxel C, Robin AC, Pla-Quintana A, Krishna TR, Recher G, Tiaho F, Caminade AM, Majoral JP, Blanchard-Desce M (2008) Brilliant organic nanodots: novel nano-objects for bionanophotonics. In: Heckman EM, Singh TB, Yoshida J (eds) Nanobiosystems: processing, characterization, and applications, Spie-Int Soc Optical Engineering, Bellingham, Vol. 7040Google Scholar
- Mongin O, Rouxel C, Vabre JM, Mir Y, Pla-Quintana A, Wei YQ, Caminade AM, Majoral JP, Blanchard-Desce M (2009) Customized multiphotonics nanotools for bioapplications: soft organic nanodots as an eco-friendly alternative to quantum dots. In: Kobayashi N, Ouchen F, Rau I (eds) Nanobiosystems: processing, characterization, and applications Ii. Proceedings of SPIE-The International Society for Optical Engineering, vol 7403. Spie-Int Soc Optical Engineering, BellinghamGoogle Scholar
- Moreno S, Szwed A, El Brahmi N, Milowska K, Kurowska J, Fuentes-Paniagua E, Pedziwiatr-Werbicka E, Gabryelak T, Katir N, de la Mata FJ, Munoz-Fernandez MA, Gomez-Ramirez R, Caminade AM, Majoral JP, Bryszewska M (2015) Synthesis, characterization and biological properties of new hybrid carbosilane-viologen-phosphorus dendrimers. RSC Adv 5(33):25942–25958. https://doi.org/10.1039/c5ra00960j CrossRefGoogle Scholar
- Neumann P, Dib H, Sournia-Saquet A, Grell T, Handke M, Caminade AM, Hey-Hawkins E (2015b) Ruthenium complexes with dendritic ferrocenyl phosphanes: synthesis, characterization, and application in the catalytic redox isomerization of allylic alcohols. Chem Eur J 21:6590–6604. https://doi.org/10.1002/chem.201406489 CrossRefGoogle Scholar
- Portevin D, Poupot M, Rolland O, Turrin CO, Fournie JJ, Majoral JP, Caminade AM, Poupot R (2009) Regulatory activity of azabisphosphonate-capped dendrimers on human CD4(+) T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy. J Transl Med 7:13. https://doi.org/10.1186/1479-5876-7-82 CrossRefGoogle Scholar
- Poupot M, Griffe L, Marchand P, Maraval A, Rolland O, Martinet L, L'Faqihi-Olive FE, Turrin CO, Caminade AM, Fournie JJ, Majoral JP, Poupot R (2006) Design of phosphorylated dendritic architectures to promote human monocyte activation. FASEB J 20:2339–2351. https://doi.org/10.1096/fj.06-5742com CrossRefGoogle Scholar
- Poupot M, Turrin CO, Caminade AM, Fournie JJ, Attal M, Poupot R, Fruchon S (2016) Poly(phosphorhydrazone) dendrimers: yin and yang of monocyte activation for human NK cell amplification applied to immunotherapy against multiple myeloma. Nanomedicine Nanotech Biol Med 12:2321–2330. https://doi.org/10.1016/j.nano.2016.07.009 CrossRefGoogle Scholar
- Rolland O, Griffe L, Poupot M, Maraval A, Ouali A, Coppel Y, Fournie JJ, Bacquet G, Turrin CO, Caminade AM, Majoral JP, Poupot R (2008) Tailored control and optimisation of the number of phosphonic acid termini on phosphorus-containing dendrimers for the ex-vivo activation of human monocytes. Chem Eur J 14:4836–4850. https://doi.org/10.1002/chem.200701063 CrossRefGoogle Scholar
- Rouxel C, Charlot M, Mongin O, Krishna TR, Caminade AM, Majoral JP, Blanchard-Desce M (2012) From graftable biphotonic chromophores to water-soluble organic nanodots for biophotonics: the importance of environmental effects. Chem Eur J 18:16450–16462. https://doi.org/10.1002/chem.201202832 CrossRefGoogle Scholar
- Sebastian RM, Magro G, Caminade AM, Majoral JP (2000) Dendrimers with N,N-disubstituted hydrazines as end groups, useful precursors for the synthesis of water-soluble dendrimers capped with carbohydrate, carboxylic or boronic acid derivatives. Tetrahedron 56(34):6269–6277. https://doi.org/10.1016/s0040-4020(00)00576-7 CrossRefGoogle Scholar
- Sebastian RM, Blais JC, Caminade AM, Majoral JP (2002) Synthesis and photochemical behavior of phosphorus dendrimers containing azobenzene units within the branches and/or on the surface. Chem Eur J 8:2172–2183. https://doi.org/10.1002/1521-3765(20020503)8:9<2172::aid-chem2172>3.0.co;2-g CrossRefGoogle Scholar
- Shakhbazau A, Mishra M, Chu TH, Brideau C, Cummins K, Tsutsui S, Shcharbin D, Majoral JP, Mignani S, Blanchard-Desce M, Bryszewska M, Yong VW, Stys PK, van Minnen J (2015) Fluorescent phosphorus dendrimer as a spectral nanosensor for macrophage polarization and fate tracking in spinal cord injury. Macromol Biosci 15:1523–1534. https://doi.org/10.1002/mabi.201500150 CrossRefGoogle Scholar
- Szwed A, Milowska K, Ionov M, Shcharbin D, Moreno S, Gomez-Ramirez R, de la Mata FJ, Majoral JP, Bryszewska M, Gabryelak T (2016) Interaction between dendrimers and regulatory proteins. Comparison of effects of carbosilane and carbosilane-viologen-phosphorus dendrimers. RSC Adv 6(100):97546–97554. https://doi.org/10.1039/c6ra16558c CrossRefGoogle Scholar
- Tomalia DA, Khanna SN (2016) A systematic framework and nanoperiodic concept for unifying nanoscience: hard/soft nanoelements, superatoms, meta-atoms, new emerging properties, periodic property patterns, and predictive Mendeleev-like nanoperiodic tables. Chem Rev 116:2705–2774. https://doi.org/10.1021/acs.chemrev.5b00367 CrossRefGoogle Scholar