Release Of Bioactive Molecules Research Articles

Self-assembled α-lactalbumin nanostructures: encapsulation and controlled release of bioactive molecules in gastrointestinal in vitro model.

Implementing encapsulation techniques is pivotal in safeguarding bioactive molecules against environmental conditions for drug delivery systems. Moreover, the food-grade nanocarrier is a delivery system and food ingredient crucial in creating nutraceutical foods. Nano α-lactalbumin has been shown to be a promissory nanocarrier for hydrophobic molecules. Furthermore, the nanoprotein can enhance the tecno-functional properties of food such as foam and emulsion. The present study investigated the nanostructured α-lactalbumin protein (nano α-la) as a delivery and controlled release system for bioactive molecules in a gastric-intestinal in vitro mimic system. The nano α-la was synthesized by a low self-assembly technique, changing the solution ionic strength by NaCl and obtaining nano α-la 191.10 ± 21.33 nm and a spherical shape. The nano α-la showed higher encapsulation efficiency and loading capacity for quercetin than riboflavin, a potential carrier for hydrophobic compounds. Thermal analysis of nano α-la resulted in a ΔH of -1480 J g-1 for denaturation at 57.44 °C. The nanostructure formed by self-assembly modifies the foam volume increment and stability. Also, differences between nano and native proteins in emulsion activity and stability were noticed. The release profile in vitro showed that the nano α-la could not hold the molecules in gastric fluid. The Weibull and Korsmeyer-Peppas model better fits the release profile behavior in the studied fluids. The present study shows the possibility of nano α-la as an alternative to molecule delivery systems and nutraceutical foods' formulation because of the high capacity to encapsulate hydrophobic molecules and the improvement of techno-functional properties. However, the nanocarrier is not perfectly suitable for the sustainable delivery of molecules in the gastrointestinal fluid, demanding improvements in the nanocarrier. © 2024 Society of Chemical Industry.

Mesoporous Fe3O4/SiO2/poly(2-carboxyethyl acrylate) composite polymer particles for pH-responsive loading and targeted release of bioactive molecules.

pH-responsive polymer microspheres undergoing reversible changes in their surface properties have been proved useful for drug delivery to targeted sites. This paper is aimed at preparing pH-responsive polymer-modified magnetic mesoporous SiO2 particles. First, mesoporous magnetic (Fe3O4) core-particles are prepared using a one-pot solvothermal method. Then, magnetic Fe3O4 particles are covered with a C[double bond, length as m-dash]C functional mesoporous SiO2 layer before seeded emulsion polymerization of 2-carboxyethyl acrylate (2-CEA). The composite polymer particles are named Fe3O4/SiO2/P(2-CEA). The average diameters of the Fe3O4 core and Fe3O4/SiO2/P(2-CEA) composite polymer particles are 414 and 595 nm, respectively. The mesoporous (pore diameter = 3.41 nm) structure of Fe3O4/SiO2/P(2-CEA) composite polymer particles is confirmed from Brunauer-Emmett-Teller (BET) surface analysis. The synthesized Fe3O4/SiO2/P(2-CEA) composite polymer exhibited pH-dependent changes in volume and surface charge density due to deprotonation of the carboxyl group under alkaline pH conditions. The change in the surface properties of Fe3O4/SiO2/P(2-CEA) composite polymer particles following pH change is confirmed from the pH-dependent sorption of cationic methylene blue (MB) and anionic methyl orange (MO) dye molecules. The opening of the pH-responsive P(2-CEA) gate valve at pH 10.0 allowed the release of loaded vancomycin up to 99% after 165 min and p-acetamido phenol (p-AP) up to 46% after 225 min. Comparatively, the amount of release is lower at pH 8.0 but still suitable for drug delivery applications. These results suggested that the mesoporous Fe3O4/SiO2 composite seed acted as a microcapsule, while P(2-CEA) functioned as a gate valve across the porous channel. The prepared composite polymer can therefore be useful for treating intestine/colon cancer, where the pH is comparatively alkaline.

Current Perspectives of Protein in Bone Tissue Engineering: Bone Structure, Ideal Scaffolds, Fabrication Techniques, Applications, Scopes, and Future Advances.

In view of their exceptional approach, excellent inherent biocompatibility and biodegradability properties, and interaction with the local extracellular matrix, protein-based polymers have received attention in bone tissue engineering, which is a multidisciplinary field that repairs and regenerates fractured bones. Bone is a multihierarchical complex structure, and it performs several essential biofunctions, including maintaining mineral balance and structural support and protecting soft organs. Protein-based polymers have gained interest in developing ideal scaffolds as emerging biomaterials for bone fractured healing and regeneration, and it is challenging to design ideal bone substitutes as perfect biomaterials. Several protein-based polymers, including collagen, keratin, gelatin, serum albumin, etc., are potential materials due to their inherent cytocompatibility, controlled biodegradability, high biofunctionalization, and tunable mechanical characteristics. While numerous studies have indicated the encouraging possibilities of proteins in BTE, there are still major challenges concerning their biodegradability, stability in physiological conditions, and continuous release of growth factors and bioactive molecules. Robust scaffolds derived from proteins can be used to replace broken or diseased bone with a biocompatible substitute; proteins, being biopolymers, provide excellent scaffolds for bone tissue engineering. Herein, recent developments in protein polymers for cutting-edge bone tissue engineering are addressed in this review within 3-5 years, with a focus on the significant challenges and future perspectives. The first section discusses the structural fundamentals of bone anatomy and ideal scaffolds, and the second section describes the fabrication techniques of scaffolds. The third section highlights the importance of proteins and their applications in BTE. Hence, the recent development of protein polymers for state-of-the-art bone tissue engineering has been discussed, highlighting the significant challenges and future perspectives.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Bioactive Release.

Microneedle arrays are minimally invasive devices that have been extensively investigated for the transdermal/intradermal delivery of drugs/bioactives. Here, we demonstrate the release of bioactive molecules (estradiol, melatonin and meropenem) from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches in vitro. The pHEMA hydrogel microneedles had mechanical properties that were sufficiently robust to penetrate soft tissues (exemplified here by phantom tissues). The bioactive release from the pHEMA hydrogel-based microneedles was fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application in the transdermal delivery of bioactives (exemplified here by estradiol, melatonin and meropenem) for the treatment of various conditions.

Application of alginate saline gel for drug delivery, cancer treatment and wound dressing

Application of alginate saline gel for drug delivery, cancer treatment and wound dressing

Vitamin B3 Containing Polymers for Nanodelivery.

Polymeric nanoparticles (NPs) with an integrated dual delivery system enable the controlled release of bioactive molecules and drugs, providingtherapeutic advantages. Key design targets include high biocompatibility, cellular uptake, and encapsulating efficiency. In this study, a polymer library derived from niacin, also known as vitamin B3 is synthesized. The library comprises poly(2-(acryloyloxy)ethyl nicotinate) (PAEN), poly(2-acrylamidoethyl nicotinate) (PAAEN), and poly(N-(2-acrylamidoethyl)nicotinamide) (PAAENA), with varying hydrophilicity in the backbone and pendant group linker. All polymers are formulated, and those with increased hydrophobicity yield NPs with homogeneous spherical distribution and diameters below 150 nm, as confirmed by scanning electron microscopy and dynamic light scattering. Encapsulation studies utilizing a model drug, neutral lipid orange (NLO), reveal the influence of polymer backbone on encapsulation efficiency. Specifically, efficiencies of 46% and 96% are observed with acrylate and acrylamide backbones, respectively. Biological investigations showed that P(AEN) and P(AAEN) NPs are non-toxic up to 300µg mL-1, exhibit superior cellular uptake, and boost cell metabolic activity. The latter is attributed to the cellular release of niacin, a precursor to nicotinamide adenine dinucleotide (NAD), a central coenzyme in metabolism. The results underline the potential of nutrient-derived polymers as pro-nutrient and drug-delivery materials.

Development of a Two-Photon-Responsive Chromophore, 2-(p-Aminophenyl)-5,6-dimethoxy-1-(hydroxyinden-3-yl)methyl Derivative, as a Photoremovable Protecting Group.

Photoremovable protecting groups (PPGs) are powerful tools that are widely used to investigate biological events in cells. An important requirement for PPGs is the efficient release of bioactive molecules by using visible to near-infrared light in the biological window (650-1350 nm). In this study, we report a new two-photon (2P)-responsive PPG, 2-(p-aminophenyl)-5,6-dimethoxy-1-(hydroxyinden-3-yl)methyl, with a donor-π-donor cyclic stilbene structure. The 2P cross section was approximately 40-50 GM at ∼700 nm. The quantum yield of the uncaging process of caged benzoate was greater than 0.7, demonstrating that the 2P uncaging efficiency was approximately 30 GM at around 700 nm. This newly developed 2P-responsive chromophore can be used in future biological experiments. The mechanism of the photo-uncaging reaction via the carbocation intermediate was elucidated using transient absorption spectroscopy and product analysis.

External Stimuli-Responsive Strategies for Surface Modification of Orthopedic Implants: Killing Bacteria and Enhancing Osteogenesis.

Bacterial infection and insufficient osteogenic activity are the main causes of orthopedic implant failure. Conventional surface modification methods are difficult to meet the requirements for long-term implant placement. In order to better regulate the function of implant surfaces, especially to improve both the antibacterial and osteogenic activity, external stimuli-responsive (ESR) strategies have been employed for the surface modification of orthopedic implants. External stimuli act as "smart switches" to regulate the surface interactions with bacteria and cells. The balance between antibacterial and osteogenic capabilities of implant surfaces can be achieved through these specific ESR manifestations, including temperature changes, reactive oxygen species production, controlled release of bioactive molecules, controlled release of functional ions, etc. This Review summarizes the recent progress on different ESR strategies (based on light, ultrasound, electric, and magnetic fields) that can effectively balance antibacterial performance and osteogenic capability of orthopedic implants. Furthermore, the current limitations and challenges of ESR strategies for surface modification of orthopedic implants as well as future development direction are also discussed.

Differences between first- and second-generation autologous platelet concentrates.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.

Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration

Tendon diseases pose a significant challenge in regenerative medicine due to the limited healing capacity of this tissue. Successful tendon regeneration requires a combination of angiogenesis, immune response, and tenogenesis processes. An effective tendon engineering (TE) strategy must finely tune this systems’ interplay toward homeostasis.This study explores in vitro the paracrine influence of amniotic epithelial stem cells (AECs) engineered on a validated 3D electrospun PLGA scaffolds on HUVECs (angiogenesis), PBMCs/Jurkat (immune response), and AECs (tenogenic stem cell activation).The results revealed the role of scaffold's topology and topography in significantly modulating the paracrine profile of the cells. In detail, AECs basal release of bioactive molecules was boosted in the cells engineered on 3D scaffolds, in particular VEGF-D, b-FGF, RANTES, and PDGF-BB (p < 0.0001 vs. CMCTR). Moreover, biological tests demonstrated 3D scaffolds' proactive role in potentiating AECs' paracrine inhibition on PBMCs proliferation (CM3Dvs. CTR, p < 0.001) and LPS-mediated Jurkat activation with respect to controls (CM3D and CM2Dvs. CTR, p < 0.01 and p < 0.05, respectively), without exerting any in vitro pro-angiogenic role in promoting HUVECs proliferation and tubule formation. Teno-inductive paracrine ability of AECs engineered on 3D scaffolds was assessed on co-cultured ones, which formed tendon-like structures. These latter demonstrated an upregulation of tendon-related genes (SCX, THBS4, COL1, and TNMD) and the expression TNMD and COL1 proteins.Overall, this research underscores the pivotal role of the 3D topology and topography of PLGA tendon mimetic scaffolds in orchestrating effective tendon regeneration through modulating cell behavior and crosstalk between engineered stem cells and different subpopulations in the damaged tendon.

Modulating the release of bioactive molecules of human mesenchymal stromal cell secretome: Heparinization of hyaluronic acid-based hydrogels

An amine derivative of hyaluronic acid (HA) was crosslinked to obtain a 3D dried sponge. The sponge was subsequently rehydrated using secretome from human mesenchymal stromal cells (MSCs), resulting in the formation of a hydrogel. The release kinetics analysis demonstrated that the hydrogel effectively sustained secretome release, with 70% of the initially loaded wound-healing-associated cytokines being released over a 12-day period. Tuning the hydrogel properties through heparin crosslinking resulted in a biomaterial with a distinct mechanism of action. Specifically, the presence of heparin enhanced water uptake capacity of the hydrogel and increased its sensitivity to enzymatic degradation. Notably, the heparin crosslinking also led to a significant retention of cytokines within the hydrogel matrix. Overall, the secretome-rehydrated HA hydrogel holds promise as a versatile device for regenerative medicine applications: the non-heparinized hydrogel may function as a biomaterial with low reabsorption rates, sustaining the release of bioactive molecules contained in MSC secretome. In contrast, the heparinized hydrogel may serve as a depot of bioactive molecules with faster reabsorption rates. Given its patch-like characteristic, the HA-based hydrogel appears suitable as topical treatment for external organs, such as the skin.

Dexamethasone release from hyaluronic acid microparticle and proanthocyanidin-gelatin hydrogel in sciatic tissue regeneration

Biodegradable microparticles are useful vehicles for the controlled release of bioactive molecules in drug delivery, tissue engineering and biopharmaceutical applications. We developed dexamethasone (Dex) encapsulation into tyramine-substituted hyaluronic acid microparticles (Dex-HA-Tyr Mp) mediated by horseradish peroxidase (HRP) crosslinking using a microfluidic device and infollowing crosslinked gelatin (Gela) with proanthocyanidin (PA) as a semi-confined bed hydrogel for the repair of sciatic tissue injury. It was found that the simultaneous use of Dex-HA-Tyr Mp and cross-linked Gela-PA hydrogel improved the physical properties of the hydrogel, including mechanical strength and degradability. The designed composite also provided a sustained release system for Dex delivery to the surrounding sites, demonstrating the applicability of the fabricated hydrogel composite for sciatic nerve tissue engineering and regeneration. The encapsulated cells were viable and showed adequate growth ability and morphogenesis during prolonged incubation in Gela-PA/HA-Tyr Mp hydrogel compared to control conditions. Interestingly, histological analysis revealed a significant increase in the number of axons in the injured sciatic nerve following treatment with Dex-HA-Tyr Mp and injectable Gela-PA hydrogel compared to other control groups. In conclusion, the results demonstrated that fabricated Dex-loaded MPs and injectable hydrogel from biomimetic components are suitable systems for sustained delivery of Dex with adequate biocompatibility and the approach may have potential therapeutic applications in peripheral nerve regeneration.Graphical

Single-cell transcriptomic analysis reveals rich pituitary-Immune interactions under systemic inflammation.

The pituitary represents an essential hub in the hypothalamus-pituitary-adrenal (HPA) axis. Pituitary hormone-producing cells (HPCs) release several hormones to regulate fundamental bodily functions under normal and stressful conditions. It is well established that the pituitary endocrine gland modulates the immune system by releasing adrenocorticotropic hormone (ACTH) in response to neuronal activation in the hypothalamus. However, it remains unclear how systemic inflammation regulates the transcriptomic profiles of pituitary HPCs. Here, we performed single-cell RNA-sequencing (scRNA-seq) of the mouse pituitary and revealed that upon inflammation, all major pituitary HPCs respond robustly in a cell type-specific manner, with corticotropes displaying the strongest reaction. Systemic inflammation also led to the production and release of noncanonical bioactive molecules, including Nptx2 by corticotropes, to modulate immune homeostasis. Meanwhile, HPCs up-regulated the gene expression of chemokines that facilitated the communication between the HPCs and immune cells. Together, our study reveals extensive interactions between the pituitary and immune system, suggesting multifaceted roles of the pituitary in mediating the effects of inflammation on many aspects of body physiology.

Sweet but Challenging: Tackling the Complexity of GAGs with Engineered Tailor-Made Biomaterials.

Glycosaminoglycans (GAGs) play a crucial role in tissue homeostasis by regulating the activity and diffusion of bioactive molecules. Incorporating GAGs into biomaterials has emerged as a widely adopted strategy in medical applications, owing to their biocompatibility and ability to control the release of bioactive molecules. Nevertheless, immobilized GAGs on biomaterials can elicit distinct cellular responses compared to their soluble forms, underscoring the need to understand the interactions between GAG and bioactive molecules within engineered functional biomaterials. By controlling critical parameters such as GAG type, density, and sulfation, it becomes possible to precisely delineate GAG functions within a biomaterial context and to better mimic specific tissue properties, enabling tailored design of GAG-based biomaterials for specific medical applications. However, this requires access to pure and well-characterized GAG compounds, which remains challenging. This review focuses on different strategies for producing well-defined GAGs and explores high-throughput approaches employed to investigate GAG-growth factor interactions and to quantify cellular responses on GAG-based biomaterials. These automated methods hold considerable promise for improving the understanding of the diverse functions of GAGs. In perspective, the scientific community is encouraged to adopt a rational approach in designing GAG-based biomaterials, taking into account the in vivo properties of the targeted tissue for medical applications.

Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

A guanosine/konjac glucomannan supramolecular hydrogel with antioxidant, antibacterial and immunoregulatory properties for cutaneous wound treatment

Developing naturally-derived wound dressing materials with intrinsic therapeutic effects is desirable for the clinical applications. Recently, guanosine-based supramolecular G-quadruplex (G4) hydrogel exhibited great potential in preparing biological materials due to its simple fabrication method and responsive gel networks. However, the weak mechanical properties and the consequent burst release of bioactive molecules restrict its clinical applications. Herein, we found that konjac glucomannan (KGM) with immunoregulatory effect did not affect the self-assembly of G-quadruplexes and thus effectively enhancing the mechanical properties of G4 hydrogel. Aloin, as a model drug, was in situ loaded into gel networks, finally obtaining the G4/Aloin-KGM hydrogel. This hydrogel exhibited porous morphology, swelling ability and hemostatic capability. Boronate bonds in G4 networks and aloin collectively endowed the hydrogel with excellent antioxidant performance. Meanwhile, aloin also provided outstanding in vitro and in vivo bactericidal ability. The wounds treated with this biocompatible hydrogel demonstrated faster regeneration of epithelial and dermal tissues, and the whole wound healing stages were accelerated by promoting collagen deposition, facilitating macrophage polarization towards M2 phenotype, down-regulating the expression level of IL-6, and up-regulating the expression level of IL-10, CD31 and α-SMA.

A Commercial Clay-Based Material as a Carrier for Targeted Lysozyme Delivery in Animal Feed.

The controlled supply of bioactive molecules is a subject of debate in animal nutrition. The release of bioactive molecules in the target organ, in this case the intestine, results in improved feed, as well as having a lower environmental impact. However, the degradation of bioactive molecules' in transit in the gastrointestinal passage is still an unresolved issue. This paper discusses the feasibility of a simple and cost-effective procedure to bypass the degradation problem. A solid/liquid adsorption procedure was applied, and the operating parameters (pH, reaction time, and LY initial concentration) were studied. Lysozyme is used in this work as a representative bioactive molecule, while Adsorbo®, a commercial mixture of clay minerals and zeolites which meets current feed regulations, is used as the carrier. A maximum LY loading of 32 mgLY/gAD (LY(32)-AD) was obtained, with fixing pH in the range 7.5-8, initial LY content at 37.5 mgLY/gAD, and reaction time at 30 min. A full characterisation of the hybrid organoclay highlighted that LY molecules were homogeneously spread on the carrier's surface, where the LY-carrier interaction was mainly due to charge interaction. Preliminary release tests performed on the LY(32)-AD synthesised sample showed a higher releasing capacity, raising the pH from 3 to 7. In addition, a preliminary Trolox equivalent antioxidant capacity (TEAC) assay showed an antioxidant capacity for the LY of 1.47 ± 0.18 µmol TroloxEq/g with an inhibition percentage of 33.20 ± 3.94%.

Near Infrared Light‐Triggered Photocatalytic Decaging for Remote‐Controlled Spatiotemporal Activation in Living Mice**

AbstractSpatiotemporal manipulation of biological processes in living animals using noninvasive, remote‐controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT‐NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT‐NIR system was demonstrated through the NIR‐triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer‐aided screening, CAT‐NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue‐penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote‐controlled rescue of drug molecules. Given its broad adaptability, this CAT‐NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.

Near Infrared Light-Triggered Photocatalytic Decaging for Remote-Controlled Spatiotemporal Activation in Living Mice.

Spatiotemporal manipulation of biological processes in living animals using noninvasive, remote-controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT-NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT-NIR system was demonstrated through the NIR-triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer-aided screening, CAT-NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue-penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote-controlled rescue of drug molecules. Given its broad adaptability, this CAT-NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.