Correction: Intelligent micro/nanorobots based on biotemplates.

Correction for 'Intelligent micro/nanorobots based on biotemplates' by Ting Chen et al., Mater. Horiz., 2024, https://doi.org/10.1039/d4mh00114a.

Intelligent micro/nanorobots based on biotemplates.

Intelligent micro/nanorobots based on natural materials as biotemplates are considered to be some of the most promising robots in the future in the microscopic field. Due to the advantages of biotemplates such as unique structure, abundant resources, environmental friendliness, easy removal, low price, easy access, and renewability, intelligent micro/nanorobots based on biotemplates can be endowed with both excellent biomaterial activity and unique structural morphology through biotemplates themselves and specific functions through artificial micro/nanotechnology. Thus, intelligent micro/nanorobots show excellent application potential in various fields from biomedical applications to environmental remediation. In this review, we introduce the advantages of using natural biological materials as biotemplates to build intelligent micro/nanorobots, and then, classify the micro/nanorobots according to different types of biotemplates, systematically detail their preparation strategies and summarize their application prospects. Finally, in order to further advance the development of intelligent micro/nanorobots, we discuss the current challenges and future prospects of biotemplates. Intelligent micro/nanorobots based on biotemplates are a perfect combination of natural biotemplates and micro/nanotechnology, which is an important trend for the future development of micro/nanorobots. We hope this review can provide useful references for developing more intelligent, efficient and safe micro/nanorobots in the future.

Ultrasound-propelled nanomotors for efficient cancer cell ferroptosis.

Ferroptosis is a non-apoptotic form of cell death that is dependent on the accumulation of intracellular iron that causes elevation of toxic lipid peroxides. Therefore, it is crucial to improve the levels of intracellular iron and reactive oxygen species (ROS) in a short time. Here, we first propose ultrasound (US)-propelled Janus nanomotors (Au-FeOx/PEI/ICG, AFPI NMs) to accelerate cellular internalization and induce cancer cell ferroptosis. This nanomotor consists of a gold-iron oxide rod-like Janus nanomotor (Au-FeOx, AF NMs) and a photoactive indocyanine green (ICG) dye on the surface. It not only exhibits accelerating cellular internalization (∼4-fold) caused by its attractive US-driven propulsion but also shows good intracellular motion behavior. In addition, this Janus nanomotor shows excellent intracellular ROS generation performance due to the synergistic effect of the "Fenton or Fenton-like reaction" and the "photochemical reaction". As a result, the killing efficiency of actively moving nanomotors on cancer cells is 88% higher than that of stationary nanomotors. Unlike previous passive strategies, this work is a significant step toward accelerating cellular internalization and inducing cancer-cell ferroptosis in an active way. These novel US-propelled Janus nanomotors with strong propulsion, efficient cellular internalization and excellent ROS generation are suitable as a novel cell biology research tool.

Dual stimuli-responsive nano-structure transition of three-arm branched amphiphilic polymers containing ferrocene (Fc) and azobenzene (Azo) moieties in aqueous solution.

Amphiphilic polymers can self-assemble into various nanostructures in solution, which can find applications in many fields such as nanotechnology, drug delivery, and template synthesis. Herein, we report the controlled self-assembly and dual stimuli-responsive nanostructure transition of a class of three-arm branched amphiphilic polymers (AzoFcPEO) containing ferrocene (Fc) and azobenzene (Azo) moieties in aqueous solution. These amphiphilic polymers were synthesized by an esterification reaction of a variety of polyethylene oxide methyl ethers (Me-PEO) with 3-(6-ferrocenyhexyloxyl)-5-(6-azobenzenehexyloxy) benzoic acid. Both the isomerization of Azo and redox of Fc moieties can respectively change the amphiphilicity of these polymers to different degrees. Consequently, these amphiphilic polymers in aqueous solution can self-assemble into various nanostructures, such as spherical micelle, worm-like micelle, spherical compound micelle, rod-like compound micelle and vesicle dependent on the PEO molecular weight, applied stimuli, and polymer concentration. This work can offer tremendous possibilities not only for the fundamental science of the controlled self-assembly but also for establishing a suitable method for regulating the nanostructures of amphiphilic polymers in aqueous solution.

Glucose-Fueled Micromotors with Highly Efficient Visible-Light Photocatalytic Propulsion.

Synthetic micro/nanomotors fueled by glucose are highly desired for numerous practical applications because of the biocompatibility of their required fuel. However, currently all of the glucose-fueled micro/nanomotors are based on enzyme-catalytic-driven mechanisms, which usually suffer from strict operation conditions and weak propulsion characteristics that greatly limit their applications. Here, we report a highly efficient glucose-fueled cuprous oxide@N-doped carbon nanotube (Cu2O@N-CNT) micromotor, which can be activated by environment-friendly visible-light photocatalysis. The speeds of such Cu2O@N-CNT micromotors can reach up to 18.71 µm/s, which is comparable to conventional Pt-based catalytic Janus micromotors usually fueled by toxic H2O2 fuel. In addition, the velocities of such motors can be efficiently regulated by multiple approaches, such as adjusting the N-CNT content within the micromotors, glucose concentrations, or light intensities. Furthermore, the Cu2O@N-CNT micromotors exhibit a highly controllable negative phototaxis behavior (moving away from light sources). Such motors with outstanding propulsion in biological environments and wireless, repeatable, and light-modulated three-dimensional motion control are extremely attractive for future practical applications.

A Review on Artificial Micro/Nanomotors for Cancer-Targeted Delivery, Diagnosis, and Therapy.

Micro/nanomotors have been extensively explored for efficient cancer diagnosis and therapy, as evidenced by significant breakthroughs in the design of micro/nanomotors-based intelligent and comprehensive biomedical platforms. Here, we demonstrate the recent advances of micro/nanomotors in the field of cancer-targeted delivery, diagnosis, and imaging-guided therapy, as well as the challenges and problems faced by micro/nanomotors in clinical applications. The outlook for the future development of micro/nanomotors toward clinical applications is also discussed. We hope to highlight these new advances in micro/nanomotors in the field of cancer diagnosis and therapy, with the ultimate goal of stimulating the successful exploration of intelligent micro/nanomotors for future clinical applications.

Linear Alternating Associative Polymer with Ultrahigh Molecular Weight: Facile Preparation by Self-Assembly Assisted Dimerization of Anthracene and Rheology in Aqueous Solution.

Alternating associative polymers (AAPs) containing more than two species of alternating hydrophobic and hydrophilic units can form unique physical network and perform interesting rheological behavior in aqueous solution. In this work, an AAP was prepared through self-assembly assisted dimerization of an anthracene-functionalized telechelic associative polymer (AnTAP) in aqueous solution by light irradiation. It is demonstrated that AnTAP can in situ chain extend to AAP with well-defined linear structure and ultrahigh molecular weight through dimerization reaction of anthracene moieties in the core of micelle under light irradiation. Meanwhile, the solution changes from viscoelastic liquid to a free-standing gel, because a physical network that cannot relax in a finite time window has developed along with the dimerization process. The results are therefore of interest not only for understanding the network structure and rheological properties of AAP solution, but also for preparing AAPs with ultrahigh molecular weight by self-assembly assisted photodimerization reactions.

Photocatalytic Micro/Nanomotors: From Construction to Applications.

Synthetic micro/nanomotors (MNMs) are a particular class of micrometer or nanometer scale devices with controllable motion behavior in solutions by transferring various energies (chemical, optical, acoustic, magnetic, electric, etc.) into mechanical energy. These tiny devices can be functionalized either chemically or physically to accomplish complex tasks in a microcosm. Up to now, MNMs have exhibited great potential in various fields, ranging from environmental remediation, nanofabrication, to biomedical applications. Recently, light-driven MNMs as classic artificial MNMs have attracted much attention. Under wireless remote control, they can perform reversible and repeatable motion behavior with immediate photoresponse. Photocatalytic micro/nanomotors (PMNMs) based on photocatalysts, one of the most important light-driven MNMs, can utilize energy from both the external light source and surrounding chemicals to achieve efficient propulsion. Unlike other kinds of MNMs, the PMNMs have a unique characteristic: photocatalytic property. On one hand, since photocatalysts can convert both optical and chemical energy inputs into mechanical propulsion of PMNMs via photocatalytic reactions, the propulsion generated can be modulated in many ways, such as through chemical concentration or light intensity. In addition, these PMNMs can be operated at low levels of optical and chemical energy input which is highly desired for more practical scenarios. Furthermore, PMNMs can be operated with custom features, including go/stop motion control through regulating an on/off switch, speed modulation through varying light intensities, direction control through adjusting light source position, and so forth. On the other hand, as superoxide radicals can be generated by photocatalytic reactions of activated photocatalysts, the PMNMs show great potential in environment remediation, especially in organic pollutant degradation. In order to construct more practical PMNMs for future applications and further extend their application fields, the ideal PMNMs should be operated in a fully environmentally friendly system with strong propulsion. In the past decade, great progress in the construction, motion regulation, and application of PMNMs has been achieved, but there are still some challenges to realize the perfect system. In this Account, we will summarize our recent efforts and those of other groups in the development toward attractive PMNM systems. First, we will illustrate basic principles about the photocatalytic reactions of photocatalysts and demonstrate how the photocatalytic reactions affect the propulsion of PMNMs. Then, we will illustrate the construction strategies for highly efficient and biocompatible PMNMs from two key aspects: (1) Improvement of energy conversion efficiency to achieve strong propulsion of PMNMs. (2) Expansion of the usable wavelengths of light to operate PMNMs in environment-friendly conditions. Next, potential applications of PMNMs have been described. In particular, environment remediation has taken major attention for the applications of PMNMs due to their photocatalytic properties. Finally, in order to promote the development of PMNMs which can be operated in fully green environments for more practical applications, an outlook of key challenges and opportunities in construction of ideal PMNMs is presented.

Controlled Self-Assembly of Multiple-Responsive Superamphiphilc Polymers Based on Host-Guest Inclusions of a Modified PEG with ß-Cyclodextrin.

Superamphiphilic polymers (SAPs) constructed by host-guest inclusion can self-assemble into various nanostructures in solution, which can find applications in many fields such as nanodevices, drug delivery, and template synthesis. Herein, we report the controlled self-assembly of multiple-responsive SAP based on a selective host-guest inclusion of ß-cyclodextrin (ß-CD) with a modified poly(ethylene glycol) (PEG) (FcC11AzoPEG) consisting of a ferrocene (Fc) end group, a C11 alkyl chain, an azobenzene (Azo) block, and a poly(ethylene glycol)methyl ether (PEG) chain. These SAPs can self-assemble into interesting nanostructures in water upon exposure to different stimuli because ß-CD can be selectively included with different guests, such as Fc, Azo, and C11 alkyl chain, under different stimuli. The inclusion complex of Fc with ß-CD (Fc@ß-CD SAP) can form nanowire micelles in aqueous solution. The nanowire micelles can be transformed into spindle micelles with the addition of oxidant because the majority of ß-CDs dissociated from the complex Fc@ß-CD SAP due to a conversion of Fc to Fc+ and will preferentially include with Azo group to form another dominant inclusion complex (Azo@ß-CD SAP). After UV irradiation, the spindle micelles can be further transformed into spherical micelles because most of ß-CDs are excluded from the complex Azo@ß-CD SAP due to a trans- to cis-Azo conversion and then form a dominant inclusion complex with C11 alkyl chains (C11@ß-CD SAP). This work not only demonstrates the selective host-guest inclusion of stimuli-responsive groups modified PEG with ß-CD but also provides a useful approach for construction of diverse morphologies.

Light-Driven Au-WO3@C Janus Micromotors for Rapid Photodegradation of Dye Pollutants.

A novel light-driven Au-WO3@C Janus micromotor based on colloidal carbon WO3 nanoparticle composite spheres (WO3@C) prepared by one-step hydrothermal treatment is described. The Janus micromotors can move in aqueous media at a speed of 16 µm/s under 40 mW/cm2 UV light due to diffusiophoretic effects. The propulsion of such Au-WO3@C Janus micromotors (diameter ∼ 1.0 µm) can be generated by UV light in pure water without any external chemical fuels and readily modulated by light intensity. After depositing a paramagnetic Ni layer between the Au layer and WO3, the motion direction of the micromotor can be precisely controlled by an external magnetic field. Such magnetic micromotors not only facilitate recycling of motors but also promise more possibility of practical applications in the future. Moreover, the Au-WO3@C Janus micromotors show high sensitivity toward extremely low concentrations of sodium-2,6-dichloroindophenol (DCIP) and Rhodamine B (RhB). The moving speed of motors can be significantly accelerated to 26 and 29 µm/s in 5 × 10-4 wt % DCIP and 5 × 10-7 wt % RhB aqueous solutions, respectively, due to the enhanced diffusiophoretic effect, which results from the rapid photocatalytic degradation of DCIP and RhB by WO3. This photocatalytic acceleration of the Au-WO3@C Janus micromotors confirms the self-diffusiophoretic mechanism and opens an opportunity to tune the motility of the motors. This work also offers the light-driven micromotors a considerable potential for detection and rapid photodegradation of dye pollutants in water.

Visible-Light-Driven BiOI-Based Janus Micromotor in Pure Water.

Light-driven synthetic micro-/nanomotors have attracted considerable attention due to their potential applications and unique performances such as remote motion control and adjustable velocity. Utilizing harmless and renewable visible light to supply energy for micro-/nanomotors in water represents a great challenge. In view of the outstanding photocatalytic performance of bismuth oxyiodide (BiOI), visible-light-driven BiOI-based Janus micromotors have been developed, which can be activated by a broad spectrum of light, including blue and green light. Such BiOI-based Janus micromotors can be propelled by photocatalytic reactions in pure water under environmentally friendly visible light without the addition of any other chemical fuels. The remote control of photocatalytic propulsion by modulating the power of visible light is characterized by velocity and mean-square displacement analysis of optical video recordings. In addition, the self-electrophoresis mechanism has been confirmed for such visible-light-driven BiOI-based Janus micromotors by demonstrating the effects of various coated layers (e.g., Al2O3, Pt, and Au) on the velocity of motors. The successful demonstration of visible-light-driven Janus micromotors holds a great promise for future biomedical and environmental applications.

Dye-Enhanced Self-Electrophoretic Propulsion of Light-Driven TiO2-Au Janus Micromotors.

Light-driven synthetic micro-/nanomotors have attracted considerable attention in recent years due to their unique performances and potential applications. We herein demonstrate the dye-enhanced self-electrophoretic propulsion of light-driven TiO2-Au Janus micromotors in aqueous dye solutions. Compared to the velocities of these micromotors in pure water, 1.7, 1.5, and 1.4 times accelerated motions were observed for them in aqueous solutions of methyl blue (10-5 g L-1), cresol red (10-4 g L-1), and methyl orange (10-4 g L-1), respectively. We determined that the micromotor speed changes depending on the type of dyes, due to variations in their photodegradation rates. In addition, following the deposition of a paramagnetic Ni layer between the Au and TiO2 layers, the micromotor can be precisely navigated under an external magnetic field. Such magnetic micromotors not only facilitate the recycling of micromotors, but also allow reusability in the context of dye detection and degradation. In general, such photocatalytic micro-/nanomotors provide considerable potential for the rapid detection and "on-the-fly" degradation of dye pollutants in aqueous environments.

Ferrocene-Functionalized Hydrophobically Modified Ethoxylated Urethane: Redox-Responsive Controlled Self-Assembly and Rheological Behavior in Aqueous Solution.

In this work, we present a novel redox-responsive ferrocene-functionalized hydrophobically modified ethoxylated urethane (Fc-HEUR) model polymer. The effects of a redox-induced hydrophobicity change of ferrocenyl hydrophobes on the self-assembly and rheological properties of Fc-HEUR in aqueous solution were investigated. In view of the redox-induced change in the hydrophilic-lipophilic balance of polymers, the Fc-HEUR polymer in aqueous solution can reversibly self-assemble into spherical micelles and larger micellar aggregates of different nanoscales and also disassemble by redox reactions immediately. Moreover, we have demonstrated that a rearrangement of micellar junctions takes place through a bridge-loop or loop-bridge transition in the concentrated polymer solution followed by redox reactions, which induces a great change in the rheological properties of the polymer solution: a viscoelastic liquid for the reduction state Fc-HEUR and a viscous liquid for the oxidation state Fc+-HEUR, owing to their different relaxation behaviors. Particularly, the associative structures and rheological properties of the Fc-HEUR aqueous solution can be reversibly controlled by redox reactions. This work will be useful not only for understanding of the thickening mechanism of stimuli-responsive HEURs but also for the development of reversible self-assembly and controlled rheological fluids, which may have some special application in drug delivery systems, catalyst supports, sensors, and microfluidic devices.

Highly Efficient Light-Driven TiO2-Au Janus Micromotors.

A highly efficient light-driven photocatalytic TiO2-Au Janus micromotor with wireless steering and velocity control is described. Unlike chemically propelled micromotors which commonly require the addition of surfactants or toxic chemical fuels, the fuel-free Janus micromotor (diameter ∼1.0 µm) can be powered in pure water under an extremely low ultraviolet light intensity (2.5 × 10(-3) W/cm(2)), and with 40 × 10(-3) W/cm(2), they can reach a high speed of 25 body length/s, which is comparable to common Pt-based chemically induced self-electrophoretic Janus micromotors. The photocatalytic propulsion can be switched on and off by incident light modulation. In addition, the speed of the photocatalytic TiO2-Au Janus micromotor can be accelerated by increasing the light intensity or by adding low concentrations of chemical fuel H2O2 (i.e., 0.1%). The attractive fuel-free propulsion performance, fast movement triggering response, low light energy requirement, and precise motion control of the TiO2-Au Janus photocatalytic micromotor hold considerable promise for diverse practical applications.

Spiropyran-Decorated SiO2-Pt Janus Micromotor: Preparation and Light-Induced Dynamic Self-Assembly and Disassembly.

The controlled self-assembly of self-propelled Janus micromotors may give the micromotors some potential applications in many fields. In this work, we design a kind of SiO2-Pt Janus catalytic micromotor functionalized by spiropyran (SP) moieties on the surface of the SiO2 hemisphere. The spiropyran-modified SiO2-Pt Janus micromotor exhibits autonomous self-propulsion in the presence of hydrogen peroxide fuel in N,N-dimethylformamide (DMF)/H2O (1:1 in volume) mixture. We demonstrate that the self-propelled Janus micromotors can dynamically assemble into multiple motors because of the electrostatic attractions and π-π stacking between MC molecules induced by UV light irradiation (λ = 365 nm) and also quickly disassemble into mono motors when the light is switched to green light (λ = 520 nm) for the first time. Furthermore, the assembled Janus motors can move together automatically with different motion patterns propelled by the hydrogen peroxide fuels upon UV irradiation. The work provides a new approach not only to the development of the potential application of Janus motors but also to the fundamental science of reversible self-assembly and disassembly of Janus micromotors.

Voltage-responsive reversible self-assembly and controlled drug release of ferrocene-containing polymeric superamphiphiles.

A new type of voltage-responsive comb-like superamphiphilic block polymer PEG113-b-PAA30/FTMA was prepared by the electrostatic interactions of an ionic ferrocenyl surfactant (FTMA) and an oppositely charged double-hydrophilic block polyelectrolyte poly-(ethylene glycol)-b-poly(acrylic acid) (PEG113-b-PAA30) in aqueous solution. An in situ electrochemical redox system was designed to research its electrochemical activity in aqueous solution. The polymeric superamphiphile PEG113-b-PAA30/FTMA could reversibly aggregate to form spherical micelles of 20-30 nm diameter in aqueous solution, and also disaggregate into irregular fragments by an electrochemical redox reaction when its concentration is in the range of the critical aggregation concentration (cacred) of the reduction state to its cacox of the oxidation state. Interestingly, above cacox, the superamphiphile can aggregate into spherical micelles of 20-30 nm diameter, which can be transformed into larger spherical micelles of 40-120 nm diameter after electrochemical oxidation, and reversibly recover initial sizes after electrochemical reduction. Moreover, this reversible self-assembly process can be electrochemically controlled just by changing its electrochemical redox extent without adding any other chemical reagent. Further, rhodamine 6G (R6G)-loaded polymeric superamphiphile aggregates have been successfully used for the voltage-controlled release of loaded molecules based on their voltage-responsive self-assembly, and the release rate of R6G could be mediated by changing electrochemical redox potentials and the concentrations of polymeric superamphiphiles. Our observations witness a new strategy to construct a voltage-responsive reversible self-assembly system.

Vapor-Driven Propulsion of Catalytic Micromotors.

Chemically-powered micromotors offer exciting opportunities in diverse fields, including therapeutic delivery, environmental remediation, and nanoscale manufacturing. However, these nanovehicles require direct addition of high concentration of chemical fuel to the motor solution for their propulsion. We report the efficient vapor-powered propulsion of catalytic micromotors without direct addition of fuel to the micromotor solution. Diffusion of hydrazine vapor from the surrounding atmosphere into the sample solution is instead used to trigger rapid movement of iridium-gold Janus microsphere motors. Such operation creates a new type of remotely-triggered and powered catalytic micro/nanomotors that are responsive to their surrounding environment. This new propulsion mechanism is accompanied by unique phenomena, such as the distinct off-on response to the presence of fuel in the surrounding atmosphere, and spatio-temporal dependence of the motor speed borne out of the concentration gradient evolution within the motor solution. The relationship between the motor speed and the variables affecting the fuel concentration distribution is examined using a theoretical model for hydrazine transport, which is in turn used to explain the observed phenomena. The vapor-powered catalytic micro/nanomotors offer new opportunities in gas sensing, threat detection, and environmental monitoring, and open the door for a new class of environmentally-triggered micromotors.

Novel ferrocenyl-terminated linear-dendritic amphiphilic block copolymers: synthesis, redox-controlled reversible self-assembly, and oxidation-controlled release.

Novel linear-dendritic amphiphilic block copolymers with hydrophilic poly(ethylene glycol) (PEG) block and hydrophobic Percec-type dendrons containing ferrocenyl terminals were synthesized by the esterification reaction of poly(ethylene glycol) methyl ether with ferrocenyl-terminated alkyl-substituted benzoic acid dendrons. On the basis of the results that the critical aggregation concentration (CACox) of the oxidation state polymer is much higher than CACred of the corresponding reduction state, these polymers can reversibly self-assemble into various aggregates, such as spherical, wormlike micelles, and vesicles, and also disassemble into irregular fragments in aqueous solution by redox reaction when changing the polymer concentrations. Copolymer PEG45-b-Fc3 (3) with 3,4,5-tris(11-ferrocenylundecyloxy) benzoic acid (2) can self-assemble into nanoscale wormlike micelles when the polymer concentration in aqueous solution is above its CACox. These wormlike micelles can be transformed into nanosized vesicles by Fe2(SO4)3 and regained by vitamin C. Interestingly, copolymer PEG45-b-Fc2 (5) with 3,5-bis(11-ferrocenylundecyloxy) benzoic acid (4) can reversibly self-assemble into spherical micelles with two different sizes by redox reaction above the CACox, indicating that the terminal hydrophobic tail number of dendrons plays a key role in determining the self-assembled structures. Furthermore, rhodamine 6G (R6G)-loaded polymer aggregates have been successfully used for the oxidation-controlled release of loaded molecules, and the release rate can be mediated by the concentrations of oxidant and copolymers. The results provide an effective approach to the reversible self-assembly of linear-dendritic amphiphilic block copolymers and also promise the potential of these novel redox-responsive amphiphilic block copolymers in drug delivery systems, catalyst supports, and other research fields.

Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents at the liquid/solid interface.

Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents (2,3,4-tri-(11-ferroncenyl)undecyloxybenzoic acid, Fc3COOH) on highly oriented pyrolytic graphite surface was investigated by scanning tunneling microscopy at the liquid/solid interface. Fc3COOH molecule formed an ordered molecular nanostructure--an alternating big/small bright dots pattern on the graphite surface extended to several hundred nanometers. On the basis of the simulation and combined with our STM results, it is concluded that the molecular adsorption conformation has an appreciable effect on the interactions of molecule-molecule and molecule-substrate. The pi-pi interactions between ferrocene groups together with the van der Waals interactions between alkyl chains direct the stacking behavior of Fc3COOH molecules. Due to the steric constraints, no hydrogen bonding between the carboxyl groups was formed during the self-assembly.

Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite shells.

Well-defined magnetic nanocomposite beads with alginate gel cores and shells of iron oxide (gamma-Fe(2)O(3)) nanoparticles were prepared by self-assembly of colloidal particles at liquid-liquid interfaces and subsequent in situ gelation. Fe(2)O(3) nanoparticles could spontaneously adsorb onto the water droplet surfaces to stabilize water-in-hexane emulsions. Water droplets containing sodium alginate were in situ gelled by calcium cations, which were released from calcium-ethylenediamine tetraacetic acid (Ca-EDTA) chelate by decreasing pH value through slow hydrolysis of d-glucono-delta-lactone (GDL). The resulting hybrid beads with a core-shell structure were easily collected by removing hexane. This facile and high efficient fabrication had a 100% yield and could be carried out at room temperature. Insulin microcrystal was encapsulated into the hybrid beads by dispersing them in the aqueous solution of alginate sodium in the fabrication process. The sustained release could be obtained due to the dual barriers of the hydrogel core and the close-packed inorganic shell. The release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The hybrid beads may find applications as delivery vehicles for biomolecules, drugs, cosmetics, food supplements and living cells.