CD-based Nanoparticles from CNR-ISMN Institute of Nanostructured Materials

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The research group of CNR-ISMN Institute of Nanostructured Materials has developed various CDE-based nanoparticles, nanoassemblies for biomedical applications.

Nanoassemblies based on poly-b-amino-cyclodextrin (PolyCD) loaded with the non-steroidal anti-inflammatory drug diclofenac (DCF) and linked by supramolecular interactions with a fluorescent probe (adamantanyl-Rhodamine conjugate, Ada-Rhod) were developed to manage inflammation in osteoarticular diseases. Biological experiments evidenced the efficient cellular internalization of PolyCD@Ada-Rhod/DCF (within two hours) without significant cytotoxicity in primary human bone marrow-derived mesenchymal stromal cells (hMSCs). PolyCD@Ada-Rhod/DCF significantly suppressed IL-1 production in hMSCs, revealing the anti-inflammatory properties of these nanoassemblies. [1]

Lithographically controlled wetting (LCW) of amphiphilic cationic b-cyclodextrins (ambCD) nanovesicles loaded with fluorescein isothiocyanate (FITC), ambCD/FITC, has been used to fabricate geometrically functionalized surfaces, thus achieving multiscale control of the cell environment. The ambCD functionalization was strongly influenced by the surface energy of the underlying substrates that, according to their hydrophobicity, orient the ambCD in a different way, thus “offering” different portions to the cells. Cell guidance and aCD/FITC cell internalization were demonstrated in human neuroblastoma SHSY5Y cells. [2]

Novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta- yclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p- oluenesulfonate) (TMPyP) were designed to fabricate efficient biocompatible systems for antimicrobial photodynamic therapy (aPDT). Release and photostability studies have been carried out under physiological conditions pointing out the role of CAPTISOL® to sustain porphyrin release for more than 2 weeks and to protect PS from photodegradation. Photoantimicrobial activity of nanoassemblies vs free porphyrin against Gram-negative P. aeruginosaE. coli and Gram-positive S. aureus was higher than the free TMPyP, nanoassemblies exhibit sustained release properties and a higher photostability thus optimizing the PDT effect at the site of action. [3]

Graphical abstract of [3]

Two medusa-like ACyDs, modified at the primary rim bearing four (ACyD4) and eight carbons (ACyD8) acyl chain length, and one bouquet-like CyD, modified at primary side with thiohexyl and at secondary one with oligoethylene moiety (SC6OH), were investigated for their ability to assemble in nanostructures or to form hybrid dipalmitoylphosphatidylcholine (DPPC)/ACyDs systems. Except for the shortest medusa-like ACyD4, the other ACyDs formed stable nanoaggregates for at least 45 days. The effect of ACyDs on the thermotropic behaviour of DPPC liposomes was also studied by differential scanning calorimetry analysis, thus elucidating their interaction with liposomes to afford hybrid liposome/ACyDs systems. [4]

The intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways were studied. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. [5]

Graphical abstract of [5]

[1] Cordaro, A., Zagami, R., Malanga, M., (…), Piperno, A., Mazzaglia, A. (2020) Cyclodextrin cationic polymer-based nanoassemblies to manage inflammation by intra-articular delivery strategies Nanomaterials 10(9),1712.

[2] Valle, F., Tortorella, S., Scala, A., (…), Biscarini, F., Mazzaglia, A. (2020) Amphiphilic cationic cyclodextrin nanovesicles: A versatile cue for guiding cell adhesion. Nanoscale Advances 2(12), pp. 5897-5904.

[3] Zagami, R., Franco, D., Pipkin, J.D., (…), Monsù Scolaro, L., Mazzaglia, A. (2020) Sulfobutylether-β-cyclodextrin/5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine nanoassemblies with sustained antimicrobial phototherapeutic action. International Journal of Pharmaceutics 585,119487.

[4] Musumeci, T., Bonaccorso, A., De Gaetano, F., (…), Puglisi, G., Ventura, C.A. (2020) A physico-chemical study on amphiphilic cyclodextrin/liposomes nanoassemblies with drug carrier potential. Journal of Liposome Research 30(4), pp. 407-416.

[5] Caccamo, D., Currò, M., Ientile, R., (…), Piperno, A., Sciortino, M.T. 2020Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration. International Journal of Molecular Sciences 21(14),4891, pp. 1-19



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