Strategies in the designing of prodrugs, taking into account the antiviral and anticancer compounds

Lesniewska-Kowiel, Monika A.; Muszalska, Izabela

doi:10.1016/j.ejmech.2017.02.011

Cited by 24 publications

(7 citation statements)

References 134 publications

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“…Efficient intracellular drug delivery has been shown for lipopeptide modified liposomal formulations where the cargo is placed into the intracellular space by membrane fusion . Moreover, targeting moieties, such as antibodies, have previously been tested as a possibility to navigate nanoparticles in the human organism with enhanced accumulation in cells expressing the targeted epitope. , However, another approach to efficiently deliver bioactive compounds into targeted areas is inspired by the concept of prodrugs, where small molecules are enzymatically activated in close vicinity of the drug target . Extending the concept would allow for the consideration of enzyme-triggered drug release of the formulated cargo as a process of bioactivation.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of PDMS–PMOXA-Based Polymersomes Sensitive to MMP-9 for Application in Breast Cancer

et al. 2018

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Cytotoxic compounds used to treat cancer are often associated with adverse events. The development of formulations activated by tumor-specific triggers would allow a reduction of systemic exposure while maintaining therapeutic concentrations in the tumor. One enzyme with proteolytic activity reported to be involved in tumor progression and assumed to be enhanced in the tumor environment is the matrix metalloproteinase 9 (MMP-9). In our study, we aimed to develop surface-modified PDMS–PMOXA polymersomes able to release their cytotoxic payload upon digestion by MMP-9. To test the applicability of such a system in breast cancer, this tumor entity was assessed for MMP-9 expression, supporting breast cancer as a potential target. The surface-modified polymersomes were synthesized and formulated resulting in paclitaxel-loaded particles of about 320 ± 153.15 nm in size with a surface potential of 0.04 ± 0.007 mV. After the expression and activity of MMP-9 in MCF7 cells were verified, this cell line was used for further analysis. Treatment of MCF7 cells with the polymersomes significantly reduced cell viability, this effect was abolished after addition of MMP-inhibitors, suggesting proteolytic activation. In zebrafish embryos, the polymersomes were observed in the circulation with some enrichment in liver and agglomerates in the caudal veins. Importantly, in zebrafish embryos xenografted with mKate2-expressing MCF7 cells, the amount of tumor cells, quantified by detecting the copies of the heterologously expressed fluorescent protein, significantly decreased after treatment with PDMS–PMOXA–SRL–paclitaxel polymersomes. Taken together, our data suggest that polymersomes modified with an MMP-9 labile peptide and loaded with paclitaxel can be formulated, and that these particles exert pharmacological activity upon enzymatic digestion.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of PDMS–PMOXA-Based Polymersomes Sensitive to MMP-9 for Application in Breast Cancer

et al. 2018

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“…to the rest of the prodrug designated as the "promoiety"; a polymer spacer, or an enzymatically cleavable spacer that can release the parent drug in the presence of a tumor-specic enzyme; and an optional targeting moiety for specic delivery to tumor cells. 14,15,50 With that in mind, there exist several key points to consider going into the design process:…”

Section: The Prodrug Approachmentioning

confidence: 99%

The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery

et al. 2021

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“…has been realized. Precursor drugs are also an important strategy for tumor-targeted drug delivery [ 106 ].…”

Section: Membrane Proteins and Their Applications In The Treatment Of Diseasesmentioning

confidence: 99%

Specifically Targeted Transport of Plasma Membrane Transporters: From Potential Mechanisms for Regulating Cell Health or Disease to Applications

2021

Membranes

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Normal substrate transport and signal transmission are the premise to ensure the health of biological somatic cells. Therefore; a comprehensive understanding of the molecular mechanism of intercellular substrate transport is of great significance for clinical treatment. In order to better understand the membrane protein through its interaction with receptors, to help maintain a healthy cell and the molecular mechanisms of disease, in this paper, we seek to clarify, first of all, the recognition mechanism for different types of membrane protein receptors; pathogen invasion using the transport pathway involved in the membrane; and the latest specific target sites of various kinds of membrane transport carriers; to provide an explanation and summary of the system. Secondly; the downstream receptor proteins and specific substrates of different membrane transporters were classified systematically; the functional differences of different subclasses and their relationship with intracellular transport disorders were analyzed to further explore the potential relationship between cell transport disorders and diseases. Finally, the paper summarizes the use of membrane transporter-specific targets for drug design and development from the latest research results; it points out the transporter-related results in disease treatment; the application prospects and the direction for drug development and disease treatment providing a new train of thought; also for disease-specific targeted therapy, it provides a certain reference value.

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Strategies in the designing of prodrugs, taking into account the antiviral and anticancer compounds

Cited by 24 publications

References 134 publications

Synthesis and Characterization of PDMS–PMOXA-Based Polymersomes Sensitive to MMP-9 for Application in Breast Cancer

Synthesis and Characterization of PDMS–PMOXA-Based Polymersomes Sensitive to MMP-9 for Application in Breast Cancer

The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery

Specifically Targeted Transport of Plasma Membrane Transporters: From Potential Mechanisms for Regulating Cell Health or Disease to Applications

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