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Bioresponsive nanomaterials are critical to developing precision medications. However, optimizing the performance of such materials in a complex environment by manipulating the response efficacy is a challenge.
Study: Polymeric Nanoreactors with Chemically Tunable Redox Responsivity. Image Credit: H_Ko/Shutterstock.com
An article published in the journal ACS Applied Materials and Interfaces discussed a new design strategy to manipulate the performance of bioresponsive materials. Here, chemically adjustable nanoreactors were developed with albumin shells and polymeric cores to achieve adjustable redox responsivity.
The in vitro characterization using dynamic light scattering (DLS) confirmed the spherical shape and particle size of nanoparticles of chemically adjustable nanoreactors. Fluorescence activation ratios of the nanoreactors were determined by varying the albumin densities on the shell.
The response sensitivity of the chemically adjustable nanoreactors to glutathione (GSH) levels was tuned by the acid−base properties of polymeric block in the core of nanoreactors, enabling the application of the nanoreactors for probe optimization in cancer imaging at histological levels and in vivo studies.
Bioresponsive Nanomaterials Toward Nanoreactors
The bioresponsive nanomaterials are applied in drug delivery, disease imaging, and tissue engineering. Smart bioresponsive nanomaterials sensitively respond to pathophysiological signals and amplify them, supporting disease imaging and precision release of therapeutics.
Bioresponsive material-based fluorescent probes are significant in cancer imaging. Stimuli-sensitive bioresponsive materials are triggered by signals of the cancerous microenvironment, including low pH and high redox levels. These probes emit strong fluorescence at the tumor site (“ON” state) and remain silent (without fluorescence emission) in normal tissues (“OFF” state).
Despite enormous efforts in exploring sensitive bioresponsive materials, most are focused on a single type of nanoprobe. Due to the lack of tunability in probe performance, the nanoprobe’s capacity to screen candidates in a complex biological environment is limited, restraining their transformation into clinical translation studies.
The performance of the bioresponsive probes depends on the fluorescence activation ratio (ON/OFF ratio) and sensitive response to 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 a lack of sensitivity toward varying target biological parameters among 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. The nanoreactors are used as a platform for developing sensing and stimuli-responsive systems.
Nanoreactors with Tunable Redox Responsivity
In the present study, chemically adjustable nanoreactors were developed to tune the bioresponsive nanoreactor's response sensitivity and fluorescence activation. Here, modifying the shell and core structures of nanoreactors controlled the chemical reaction process and the resulting products.
Nanoreactors have the similarity of principles to bioresponsive nanomaterials. Hence, these stimuli-sensitive nanomaterials were regarded as nanoreactors. Here, the stimulus enters the core, accelerates chemical reactions, and releases the products into shells.
The chemically adjustable nanoreactors showed tunable response efficacy under different redox levels. The fluorophore-conjugated polymeric core of nanoreactors consisted of polymers with indocyanine green-conjugated redox-sensitive disulfide bonds. On the other hand, the shell was composed of bovine serum albumins with a strong affinity toward indocyanine green dye molecules.
In a non-reductive environment (in healthy cells), the fluorescence quenching of indocyanine green dye in the hydrophobic core suppressed the background signals and silenced the nanoreactors. On the other hand, in a redox environment of tumor cells, the GSH diffused into the core of the nanoreactor to accelerate the redox reaction, releasing indocyanine green dye and activating the fluorescence effect.
Modifying the nanoreactor's core with different tertiary amines tuned its acid-base properties, regulating the GSH diffusion amount into the core that affected the extent of redox reaction or GSH response sensitivity. Alternatively, modifying the density of bovine albumin serum on the shell tuned the fluorescence activation of the chemically adjustable nanoreactors.
Thus, manipulating the response efficacy to the external stimulus was critical to optimizing bioresponsive materials suitable for highly complex environments. The performance and efficacy of the bioresponsive nanoparticles were determined as two important criteria for their application in disease imaging and target-specific drug delivery.
Conclusion
Overall, fluorescent nanoreactors were developed consisting of polymer cores and albumin shells. These nanoreactors were conjugated with dyes and sensitive toward GSH. The developed nanoreactors could tune redox response sensitivity, determined by the shell-regulated, albumin density-based fluorescence activation efficacy and the chemical structure of the core.
The manipulative fluorescent nanoreactor’s performance allowed their application for probe optimization in cancer imaging. The chemically alterable nanoreactors developed in the present work offered a promising strategy for tuning response efficacy and performance of bioresponsive materials and optimizing the bioresponsive probes in precision cancer imaging.
Reference
Gong, L et al. (2022). Polymeric Nanoreactors with Chemically Tunable Redox Responsivity. ACS Applied Materials and Interfaces. https://pubs.acs.org/doi/10.1021/acsami.2c07663