Effect of drug precursor in cell uptake and cytotoxicity of redox-responsive camptothecin nanomedicines

Botella, Pablo; Muniesa, Carlos; Vicente, Víctor Moreira; Cabrera-García, Alejandro

doi:10.1016/j.msec.2015.09.012

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…No cell enlargement was observed (as expected for a DNA damaging agent like CPT), indicating that, even if nanoparticles carrying the drug are internalized, in these experimental conditions the drug is not able to get into nucleus and block the enzyme topoisomerase I. Actually, as already shown in different DDSs [53],…”

Section: Biological Validationsupporting

confidence: 54%

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems

Oliveira

Rivero-Buceta

Vidaurre-Agut

et al. 2020

Materials Science and Engineering: C

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Section: Biological Validationsupporting

confidence: 54%

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems

Oliveira

Rivero-Buceta

Vidaurre-Agut

et al. 2020

Materials Science and Engineering: C

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“…Additional incorporation of a fluorophore into particles core facilitated imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa human cervix carcinoma cells confirmed that nanoparticles enter in a separated study [174], it was shown that prodrug side chain carbon number (n) determines material hydrophobic properties and, as a consequence, its stability in aqueous medium and cell uptake kinetics. When n value increases, the negative surface charge decreases dramatically due to a shielding effect provoked by hydrophobic ligands, which promotes particle aggregation and favors cell internalization.…”

Section: Redox-sensitive Systemsmentioning

confidence: 90%

Safe approaches for camptothecin delivery: Structural analogues and nanomedicines

Botella

Rivero-Buceta

2017

Journal of Controlled Release

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Twenty-(S)-camptothecin is a strongly cytotoxic molecule with excellent antitumor activity over a wide spectrum of human cancers. However, the direct formulation is limited by its poor water solubility, low plasmatic stability and severe toxicity, which currently limits its clinical use. As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines. In this review, we summarize recent advances in the design, synthesis and development of camptothecin molecular derivatives and supramolecular vehicles, following a systematic classification according to structure-activity relationships (structural analogues) or chemical nature (nanomedicines). A series of organic, inorganic and hybrid materials are presented as nanoplatforms to overcome camptothecin restrictions in administration, biodistribution, pharmacokinetics and toxicity. Nanocarriers which respond to a variety of stimuli endogenously (e.g., pH, redox potential, enzyme activity) or exogenously (e.g., magnetic field, light, temperature, ultrasound) seem the best positioned therapeutic materials for optimal spatial and temporal control over drug release. The main goal of this review is to be used as a source of relevant literature for others interested in the field of camptothecin-based therapeutics. To this end, final remarks on the most important formulations currently under clinical trial are provided.

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“…More recently, our group has developed different redox-responsive nanoplatforms through a new synthetic strategy, based on the direct conjugation of (pyridin-2yldisulfanyl)alkyl carbonate derivatives of CPT with cleavable disulfide linkers to hybrid SNPs containing a non-porous core and a mesoporous shell [23,24]. This research aims to In addition, different tests were performed at different pH values to determine the effect of the functionalization of the pore walls and the presence of the polymer coating on the release of sulforhodamine B (SRB).…”

Section: Redox-responsive Systemsmentioning

confidence: 99%

“…In addition, with the incorporation of a fluorophore into the nanoparticles, it has been possible to determine by confocal microscopy in HeLa cells that the entry of the nanoparticles into the cells occurs by endocytosis. To complete this work, we determined how the incorporation of CPT prodrugs with different number of carbons in the side chain affects the properties of hybrid porous SNPs [24]. The most important conclusion is that the number of side-chains determines the properties of the resulting materials, including hydrophobic properties, and the type of released products and cytotoxic activity.…”

Section: Redox-responsive Systemsmentioning

confidence: 99%

Silica-Based Stimuli-Responsive Systems for Antitumor Drug Delivery and Controlled Release

2022

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The administration of cytotoxic drugs in classical chemotherapy is frequently limited by water solubility, low plasmatic stability, and a myriad of secondary effects associated with their diffusion to healthy tissue. In this sense, novel pharmaceutical forms able to deliver selectively these drugs to the malign cells, and imposing a space-time precise control of their discharge, are needed. In the last two decades, silica nanoparticles have been proposed as safe vehicles for antitumor molecules due to their stability in physiological medium, high surface area and easy functionalization, and good biocompatibility. In this review, we focus on silica-based nanomedicines provided with specific mechanisms for intracellular drug release. According to silica nature (amorphous, mesostructured, and hybrids) nanocarriers responding to a variety of stimuli endogenously (e.g., pH, redox potential, and enzyme activity) or exogenously (e.g., magnetic field, light, temperature, and ultrasound) are proposed. Furthermore, the incorporation of targeting molecules (e.g., monoclonal antibodies) that interact with specific cell membrane receptors allows a selective delivery to cancer cells to be carried out. Eventually, we present some remarks on the most important formulations in the pipeline for clinical approval, and we discuss the most difficult tasks to tackle in the near future, in order to extend the use of these nanomedicines to real patients.

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Effect of drug precursor in cell uptake and cytotoxicity of redox-responsive camptothecin nanomedicines

Cited by 12 publications

References 44 publications

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems

Safe approaches for camptothecin delivery: Structural analogues and nanomedicines

Silica-Based Stimuli-Responsive Systems for Antitumor Drug Delivery and Controlled Release

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