Bioresponsive nanomaterials are central to developing precision medicine. However, optimizing the performance of these materials in a complex environment by manipulating the response efficacy is challenging.
Study: Polymeric nanoreactors with chemically adjustable redox response. Image credit: H_Ko/Shutterstock.com
A paper published in the journal ACS Applied Materials and Interfaces discussed a new design strategy to manipulate the performance of bioresponsive materials. Here, chemically tunable nanoreactors with albumin shells and polymeric cores were developed to achieve a tunable redox response.
In vitro characterization by dynamic light scattering (DLS) confirmed the spherical shape and particle size of the chemically tunable nanoreactor nanoparticles. The fluorescence activation ratios of the nanoreactors were determined by varying the albumin densities in the shell.
The response sensitivity of the chemically tunable nanoreactors to glutathione (GSH) levels was tuned by the acid-base properties of the polymeric block in the core of the nanoreactors, allowing the application of the nanoreactors for the optimization of cancer imaging probes in histological level and in vivo studies. .
Bioresponsive nanomaterials towards nanoreactors
Bioresponsive nanomaterials are applied in drug delivery, disease imaging and tissue engineering. Bioresponsive smart nanomaterials sensitively respond to and amplify pathophysiological signals, supporting disease imaging and precision release of therapeutics.
Fluorescent probes based on bioresponsive material are important in cancer imaging. Stimuli-sensitive bioresponsive materials are triggered by signals from the cancer microenvironment, including low pH and high redox levels. These probes emit strong fluorescence at the tumor site (“ON” state) and remain silent (no fluorescence emission) in normal tissues (“OFF” state).
Despite enormous efforts to explore sensitive bioresponsive materials, most focus on a single type of nanoprobe. Due to the lack of tuning in probe performance, the ability of the nanoprobe to select candidates in a complex biological environment is limited, limiting its transformation into clinical translational studies.
The performance of bioresponsive probes depends on the fluorescence activation ratio (ON/OFF ratio) and the sensitive response to the stimuli. However, most reported nanoprobes were tested against high stimulus levels in vitro or in vivo.
An additional challenge of existing bioresponsive materials sensitive to endogenous stimuli is the lack of sensitivity to variable target biological parameters between patients and significant differences in the biological environment in human and animal models.
Nanoreactors are nanocontainers with an internal cavity and the ability to encapsulate one or more guests. Nanoreactors are used as a platform to develop sensing and stimulus response systems.
Nanoreactors with adjustable redox response
In the present study, chemically tunable nanoreactors were developed to tune the response sensitivity of the bioresponsive nanoreactor and fluorescence activation. Here, the modification of the shell and core structures of the nanoreactors controlled the chemical reaction process and the resulting products.
Nanoreactors have similar principles to bioresponsive nanomaterials. Therefore, these stimuli-responsive nanomaterials were considered nanoreactors. Here, the stimulus enters the core, speeds up chemical reactions, and releases products into the shells.
Chemically tunable nanoreactors showed tunable response efficiency at different redox levels. The fluorophore-conjugated polymeric core of the nanoreactors consisted of polymers with redox-sensitive disulfide bonds conjugated with indocyanine green. On the other hand, the shell was composed of bovine serum albumins with a strong affinity towards indocyanine green dye molecules.
In a nonreducing environment (in healthy cells), quenching the fluorescence of the indocyanine green dye in the hydrophobic core suppressed background signals and silenced the nanoreactors. On the other hand, in a redox environment of tumor cells, GSH diffused into the core of the nanoreactor to accelerate the redox reaction, releasing the indocyanine green dye and activating the fluorescence effect.
Modification of the nanoreactor core with different tertiary amines tuned its acid-base properties, regulating the amount of GSH diffusion into the core that affected the extent of the redox reaction or the sensitivity of the GSH response. Alternatively, modification of the density of bovine serum albumin in the shell tuned the fluorescence activation of the chemically tunable nanoreactors.
Therefore, manipulating the efficacy of the response to the external stimulus was critical to optimize bioresponsive materials suitable for highly complex environments. The performance and efficacy of bioresponsive nanoparticles were determined as two important criteria for their application in disease imaging and target-specific drug delivery.
conclusion
In general, fluorescent nanoreactors consisting of polymer cores and albumin shells were developed. These nanoreactors were conjugated with dyes and were sensitive to GSH. The developed nanoreactors could tune the sensitivity of the redox response, determined by the efficiency of fluorescence activation based on the albumin density regulated by the shell and the chemical structure of the core.
The performance of the manipulative fluorescent nanoreactor allowed its application for probe optimization in cancer imaging. The chemically alterable nanoreactors developed in the present work offered a promising strategy for tuning the response efficacy and performance of bioresponsive materials and optimizing bioresponsive probes in precision cancer imaging.
reference
Gong, L et al. (2022). Polymeric nanoreactors with chemically tunable redox response. ACS applied materials and interfaces. https://pubs.acs.org/doi/10.1021/acsami.2c07663
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