Dendrimer nanoparticles for colorectal cancer applications

Carvalho, Mariana R.; Reis, Rui L.; Oliveira, Joaquím M.

doi:10.1039/c9tb02289a

Cited by 97 publications

(55 citation statements)

References 96 publications

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“…Dendritic polymers have been widely explored for a series of applications, ranging from electronics to biomaterials. Several dendrimers have been considered in clinical trials, due to their advanced properties, when it comes to structural control at the nanometer scale [ 37 ]. Dendritic polyglycerols (PG) of hyperbranched character possess a variety of OH groups (linear and dendritic) that are easy to functionalize, with high control on their loading and position [ 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

et al. 2020

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Macrophages are hosts for intracellular pathogens involved in numerous diseases including leishmaniasis. They express surface receptors that may be exploited for specific drug-targeting. Recently, we developed a PEGylated dendritic polyglycerol-based conjugate (PG–PEG) that colocalizes with intracellular parasite. We hereby study the effect of surface decoration with mannose units on the conjugates’ targeting ability toward leishmania intracellular parasites. Murine and human macrophages were exposed to fluorescently labeled mannosylated PG–PEG and uptake was quantified by flow cytometry analysis. Nanocarriers bearing five mannose units showed the highest uptake, which varied between 30 and 88% in the population in human and murine macrophages, respectively. The uptake was found to be dependent on phagocytosis and pinocytosis (80%), as well as clathrin-mediated endocytosis (79%). Confocal microscopy showed that mannosylated PG–PEGs target acidic compartments in macrophages. In addition, when both murine and human macrophages were infected and treated, colocalization between parasites and mannosylated nanoconjugates was observed. Leishmania-infected bone marrow-derived macrophages (BMM) showed avidity by mannosylated PG–PEG whereas non-infected macrophages rarely accumulated conjugates. Moreover, the antileishmanial activity of Amphotericin B was kept upon conjugation to mannosylated PG–PEG through a pH-labile linker. This study demonstrates that leishmania infected macrophages are selectively targeted by mannosylated PEGylated dendritic conjugates.

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Section: Resultsmentioning

confidence: 99%

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

et al. 2020

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“…Dendrimers continue to be the subject of a very broad range of investigations, with applications ranging from drug delivery [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ], catalysis [ 72 , 73 ], hydrogels [ 74 ], fingerprint detection [ 75 ], and optical data storage [ 76 ]. The structural diversity of dendrimers is indeed broad, not only in terms of the dendrimer skeleton but also in terms of functionalization with the chemical conjugates, and post synthesis manipulations, which broadens the scope of dendrimers and dendrons for varied utility [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. Dendron is the term used for a smaller section of the dendrimer, with a similar build-up, containing a focal point and monodisperse hyperbranched backbone.…”

Section: Dendrimers/dendronsmentioning

confidence: 99%

Telodendrimers: Promising Architectural Polymers for Drug Delivery

Mejlsøe

Kakkar

2020

Molecules

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Architectural complexity has played a key role in enhancing the efficacy of nanocarriers for a variety of applications, including those in the biomedical field. With the continued evolution in designing macromolecules-based nanoparticles for drug delivery, the combination approach of using important features of linear polymers with dendrimers has offered an advantageous and viable platform. Such nanostructures, which are commonly referred to as telodendrimers, are hybrids of linear polymers covalently linked with different dendrimer generations and backbones. There is considerable variety in selection from widely studied linear polymers and dendrimers, which can help tune the overall composition of the resulting hybrid structures. This review highlights the advances in articulating syntheses of these macromolecules, and the contributions these are making in facilitating therapeutic administration. Limited progress has been made in the design and synthesis of these hybrid macromolecules, and it is through an understanding of their physicochemical properties and aqueous self-assembly that one can expect to fully exploit their potential in drug delivery.

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“…The model reaction (Figures S2 and S3 and Table S1) was carried out to allow interpretation of complex NMR spectra of nanoconjugates (4)(5)(6)(7)(8)(9). The POSS structure-T 8 [(CH 2 ) 2 S(CH 2 ) 2 OH] 8 applied in the model reaction has a well-defined structure, in contrast to [POSS(OH) 32 ] being a mixture of cage silsesquioxanes.…”

Section: Model Reactionmentioning

confidence: 99%

“…We are currently witnessing a rapid development of anticancer drug delivery systems [1,2], exploiting such nanocarriers as, e.g., gold and mesoporous silica nanoparticles, polymers, and dendrimers [3]. Nanotechnology and nanomedicine [4,5] now offer a variety of systems that are intensively studied as delivery vehicles, modulating cytotoxicity and mediating sustained drug release in tumour tissues.…”

Section: Introductionmentioning

confidence: 99%

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers—Potential Anticancer Prodrugs

2020

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Anthracyclines belong to the anticancer drugs that are widely used in chemotherapy. However, due to their systemic toxicity they also exert dangerous side effects associated mainly with cardiovascular risks. The pathway that is currently often developed is their chemical and physical modification via formation of conjugated or complexed prodrug systems with a variety of nanocarriers that can selectively release the active species in cancer cells. In this study, six new nanoconjugates were synthesized with the use of polyhedral oligosilsesquioxanes [POSS(OH)32] as nanocarriers of the anticancer drugs anthracyclines—doxorubicin (DOX) and daunorubicin (DAU). These prodrug conjugates are also equipped with poly(ethylene glycol) (PEG) moieties of different structure and molecular weight. Water-soluble POSS, succinic anhydride modified (SAMDOX and SAMDAU) with carboxylic function, and PEGs (PEG1, PEG2 and PEGB3) were used for the synthesis. New nanoconjugates were formed via ester bonds and their structure was confirmed by NMR spectroscopy (1H-NMR, 13C-NMR, 1H-13C HSQC, DOSY and 1H-1H COSY), FTIR and DLS. Drug release rate was evaluated using UV-Vis spectroscopy at pH of 5.5. Release profiles of anthracyclines from conjugates 4–9 point to a range of 10 to 75% (after 42 h). Additionally, model NMR tests as well as diffusion ordered spectroscopy (DOSY) confirmed formation of the relevant prodrugs. The POSS-anthracycline conjugates exhibited prolonged active drug release time that can lead to the possibility of lowering administered doses and thus giving them high potential in chemotherapy. Drug release from conjugate 7 after 42 h was approx. 10%, 33% for conjugate 4, 47% for conjugate 5, 6, 8 and 75% for conjugate 9.

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Dendrimer nanoparticles for colorectal cancer applications

Abstract: Routes of dendrimer synthesis and the stages of possible applicability of dendrimer nanoparticles in the case of colorectal cancer.

Cited by 97 publications

References 96 publications

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

Telodendrimers: Promising Architectural Polymers for Drug Delivery

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers—Potential Anticancer Prodrugs

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