Light‐Responsive,Singlet‐Oxygen‐Triggered On‐Demand Drug Release from Photosensitizer‐Doped Mesoporous Silica Nanorods for Cancer Combination Therapy

Smart drug delivery systems with on‐demand drug release capability are rather attractive to realize highly specific cancer treatment. Herein, a novel light‐responsive drug delivery platform based on photosensitizer chlorin e6 (Ce6) doped mesoporous silica nanorods (CMSNRs) is developed for on‐demand light‐triggered drug release. In this design, CMSNRs are coated with bovine serum albumin (BSA) via a singlet oxygen (SO)‐sensitive bis‐(alkylthio)alkene (BATA) linker, and then modified with polyethylene glycol (PEG). The obtained CMSNR‐BATA‐BSA‐PEG, namely CMSNR‐B‐PEG, could act as a drug delivery carrier to load with either small drug molecules such as doxorubicin (DOX), or larger macromolecules such as cis‐Pt (IV) pre‐drug conjugated third generation dendrimer (G3‐Pt), both of which are sealed inside the mesoporous structure of nanorods by BSA coating. Upon 660 nm light irradiation with a rather low power density, CMSNRs with intrinsic Ce6 doping would generate SO to cleave BATA linker, inducing detachment of BSA‐PEG from the nanorod surface and thus triggering release of loaded DOX or G3‐Pt. As evidenced by both in vitro and in vivo experiments, such CMSNR‐B‐PEG with either DOX or G3‐Pt loading offers remarkable synergistic therapeutic effects in cancer treatment, owing to the on‐demand release of therapeutics specifically in the tumor under light irradiation.     

CelloMOF: Nanocellulose Enabled 3D Printing of Metal–Organic Frameworks

3D printing is recognized as a powerful tool to develop complex geometries for a variety of materials including nanocellulose. Herein, a one‐pot synthesis of 3D printable hydrogel ink containing zeolitic imidazolate frameworks (ZIF‐8) anchored on anionic 2,2,6,6‐tetramethylpiperidine‐1‐oxylradical‐mediated oxidized cellulose nanofibers (TOCNF) is presented. The synthesis approach of ZIF‐8@TOCNF (CelloZIF8) hybrid inks is simple, fast (≈30 min), environmentally friendly, takes place at room temperature, and allows easy encapsulation of guest molecules such as curcumin. Shear thinning properties of the hybrid hydrogel inks facilitate the 3D printing of porous scaffolds with excellent shape fidelity. The scaffolds show pH controlled curcumin release. The synthesis route offers a general approach for metal–organic frameworks (MOF) processing and is successfully applied to other types of MOFs such as MIL‐100 (Fe) and other guest molecules as methylene blue. This study may open new venues for MOFs processing and its large‐scale applications.     

Zeolitic Imidazole Framework: Metal–Organic Framework Subfamily Members for Triboelectric Nanogenerators

Zeolitic imidazole framework (ZIF), a subfamily of metal–organic framework (MOF), offers excellent chemical and thermal stability in addition to other MOF advantages. The triboelectric series predominantly consist of few metals and mainly polymers that are not suitable for the development of sensors with high selectivity and specificity. The development of multifunctional, tunable materials is of utmost importance for extending the applications of a triboelectric nanogenerator (TENG). The TENG based on the ZIF subfamily materials (ZIF‐7, ZIF‐9, ZIF‐11, and ZIF‐12) is reported here. The surface roughness, structural, morphological, and surface potential analysis reveals the detailed characteristics of the ZIF family members. The ZIFs and Kapton are used as triboelectric layers for the ZIF‐TENG fabrication. The device is analyzed in detail for its electrical performance (voltage, current, charge, stability, load matching analysis, and capacitor charging). The ZIF‐7 TENG generates the highest output of 60 V and 1.1 µA in vertical contact‐separation mode. Finally, various low‐power electronics are successfully driven with the capacitor charged by the output of the ZIF‐7 TENG.     

A Near‐Infrared Light‐Triggered Nanocarrier with Reversible DNA Valves for Intracellular Controlled Release

A near‐infrared (NIR) light‐triggered nanocarrier is developed for intracellular controlled release with good stability, high nuclease resistance, and good biocompatibility. The nanocarrier consists of a gold nanorod core and mesoporous silica shell, capped with reversible single‐stranded DNA valves, which are manipulated by switching between the laser on/off states. Upon laser irradiation, the valves of the nanocarrier open and the cargo molecules can be released from the mesopores. When the NIR laser is turned off, the valves close and the nanocarrier stops releasing the cargo molecules. The release amount of the cargo molecules can be controlled precisely by adjusting the irradiation time and the laser on‐off cycles. Confocal fluorescence imaging shows that the nanocarrier can be triggered by the laser irradiation and the controlled release can be accomplished in living cells. Moreover, the therapeutic effect toward cancer cells can also be regulated when the chemotherapeutic drug doxorubicin is loaded into the nanocarrier. This novel approach provides an ideal platform for drug delivery by a NIR light‐activated mechanism with precise control of area, time, and especially dosage.     

Enzyme‐Driven Release of Loads from Nucleic Acid–Capped Metal–Organic Framework Nanoparticles

Nucleic acid–modified UiO‐68 metal–organic framework nanoparticles, NMOFs, are loaded with the anticancer drug camptothecin (or drug models), and the loaded NMOFs are capped with sequence‐specific duplex units. The NMOFs are unlocked by the biocatalytic decomposition of the duplex capping units that result in the release of the drug (or drug models). The enzymes used are DNase I, a nicking enzyme (Nt.BbvCI), an endonuclease (EcoRI), and an exonuclease III (Exo III). Camptothecin‐loaded NMOFs, capped by tailored hairpin nucleic acids being cooperatively unlocked by adenosine triphosphate (ATP), that is overexpressed in cancer cells, and Exo III are prepared. The camptothecin‐loaded NMOFs reveal that selective cytotoxicity toward MDA‐MB‐231 cancer cells and ≈55% apoptosis of the cancer cells is observed after 5 days of treatment with the NMOFs, while only ≈15% apoptosis of epithelial MCF‐10A breast cells is observed.     

Near‐Infrared Light‐Encoded Orthogonally Triggered and Logical Intracellular Release Using Gold Nanocage@Smart Polymer Shell

Gold nanocages (AuNCs) with hollow interiors, porous walls, and tunable localized surface plasmon resonance (LSPR) peaks in the NIR region represent a promising platform for therapeutic applications, and can be used for orthogonally triggered release by choosing the right laser according to the AuNC's LSPR. AuNCs are prepared with different LSPRs and covered with a smart polymer shell. Laser irradiation in resonance with the LSPR can trigger the release of a pre‐loaded effector. As a proof of concept, enzyme and substrate (prodrug) are selectively released from two different AuNCs. Enzymatic reactions only occur after successful opening of both types of AuNC capsules. The system acts as an “AND” logic gate. Furthermore, if the AuNC is loaded with isoenzyme or enzyme inhibitor, an “OR” or “INHIBIT” logic gate operation is achieved. To the best of our knowledge, no reports have combined NIR light‐encoded orthogonally triggered release with “prodrug” activation processes to realize defined different logic operations for regulating the dosage of active drug in a specific region. The design is simple and spatial/temporal to control, and provides new insights into developing NIR light‐encoded, logically controlled, intracellular release systems.     

Remotely Controlled Red Blood Cell Carriers for Cancer Targeting and Near‐Infrared Light‐Triggered Drug Release in Combined Photothermal–Chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus‐responsive, RBC‐based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near‐infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light‐induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC‐based cancer cell targeted drug delivery and light‐controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.     

ATP‐Responsive Aptamer‐Based Metal–Organic Framework Nanoparticles (NMOFs) for the Controlled Release of Loads and Drugs

Nanoparticles consisting of metal–organic frameworks (NMOFs) modified with nucleic acid binding strands are synthesized. The NMOFs are loaded with a fluorescent agent or with the anticancer drug doxorubicin, and the loaded NMOFs are capped by hybridization with a complementary nucleic acid that includes the ATP‐aptamer or the ATP‐AS1411 hybrid aptamer in caged configurations. The NMOFs are unlocked in the presence of ATP via the formation of ATP‐aptamer complexes, resulting in the release of the loads. As ATP is overexpressed in cancer cells, and since the AS1411 aptamer recognizes the nucleolin receptor sites on the cancer cell membrane, the doxorubicin‐loaded NMOFs provide functional carriers for targeting and treatment of cancer cells. Preliminary cell experiments reveal impressive selective permeation of the NMOFs into MDA‐MB‐231 breast cancer cells as compared to MCF‐10A normal epithelial breast cells. High cytotoxic efficacy and targeted drug release are observed with the ATP‐AS1411‐functionalized doxorubicin‐loaded NMOFs.     

Compartmentalization within Self‐Assembled Metal–Organic Framework Nanoparticles for Tandem Reactions

Compartmentalization is an essential feature found in living cells to ensure multiple biological processes occur without being affected by undesired external influences. Here, compartmentalized systems are developed based on the self‐assembly of metal–organic framework (MOF) nanoparticles into multifunctional MOF capsules (MOF‐Cs). Such MOF‐Cs have the capability of controlling molecular transportation and protecting interior microenvironment, thus making tandem reaction along trajectories to desired products. First of all, MOF‐Cs present controlled molecular transportation derived from molecular sieving property of MOFs. Second, MOF‐Cs can protect the encapsulated cargoes from denaturation and maintain their catalytic activity. Third, MOF‐Cs can provide spatial segregation for incompatible species and facilitate communication between these compartments to perform tandem reactions. These compartmentalized structures offer new views in the transportation, microreactor, and biotechnology.     

Metal–Organic Framework Assisted and Tumor Microenvironment Modulated Synergistic Image‐Guided Photo‐Chemo Therapy

The complex tumor microenvironment (TME) and nonspecific drug targeting limit the clinical efficacy of photodynamic therapy in combination with chemotherapy. Herein, a metal–organic framework (MOF) assisted strategy is reported that modulates TME by reducing tumor hypoxia and intracellular glutathione (GSH) and offers targeted delivery and controlled release of the trapped chemodrug. Platinum(IV)‐diazido complex (Pt(IV)) is loaded inside a Cu(II) carboxylate‐based MOF, MOF‐199, and an aggregation‐induced‐emission photosensitizer, TBD, is conjugated to polyethylene glycol for encapsulating Pt(IV)‐loaded MOF‐199. Once the fabricated TBD‐Pt(IV)@MOF‐199 nanoparticles are internalized by cancer cells, MOF‐199 consumes intracellular GSH and decomposes to fragments to release Pt(IV). Upon light irradiation, the released Pt(IV) generates O₂ that relieves hypoxia and produces Pt(II)‐based chemodrug inside cancer cells. Concomitantly, efficient reactive oxygen species generation and bright emission are afforded by TBD, resulting in synergistic image‐guided photo‐chemo therapy with enhanced efficacies and mitigated side effects.     

Visible Light Triggered CO2 Liberation from Silver Nanocrystals Incorporated Metal–Organic Frameworks

Widespread deployment of metal–organic frameworks (MOFs) for CO₂ capture remains challenging due to the great energy‐penalty associated with their regeneration. To overcome this challenge, a new type of photodynamic carbon capture material synthesized by incorporating Ag nanocrystals with UiO‐66 (Ag/UiO‐66) framework is presented. Upon the irradiation of visible light, Ag nanocrystals within the composites serve as “nanoheaters” to convert photon energy into thermal energy locally. Driven by such light‐induced localized heat (LLH), the adsorbed CO₂ within MOFs is remotely released. The CO₂ desorption capacity of such Ag/UiO‐66 composites can be readily regulated by control over their Ag contents and the applied light intensity. Up to 90.5% of CO₂ desorption is achieved under the investigated conditions. Distinct from the traditional light‐responsive MOFs for gas trigger release, currently developed LLH‐driven CO₂ release method not only offers a promising solution to the heat‐insulating nature of MOFs, but also demonstrates a potentially low energy method to remotely regenerate MOF adsorbents given the utilization of naturally abundant visible light as efficient stimulus.     

Engineering Zeolitic‐Imidazolate Framework (ZIF) Thin Film Devices for Selective Detection of Volatile Organic Compounds

Thin films of sodalite‐type zeolitic‐imidazolate frameworks (ZIFs, ZIF‐7, 8, 9, 67, 90, and ZIF‐65‐Zn) with different metal centers and functional moieties are fabricated on SiO₂ coated quartz crystal microbalance (QCM) substrates using automatic program controlled repeated direct growth method. The repeated direct growth procedure manipulated here shows great applicability for rapid growth of uniform ZIF thin films with controllable thickness. The fabricated ZIF/QCM devices are used to detect vapor phase volatile organic compounds including alcohol/water, BTEX compounds (benzene, toluene, ethylbenzene and xylene isomers), and hexane isomers. The ZIF/QCM devices exhibit selective detection behavior upon exposure to these chemical vapors. The effects of ZIF pore size, limited pore diameter, surface functionality, and structural flexibility on the sensing performances of ZIF/QCM devices are systematically investigated, which would be beneficial for the practical application of ZIF sensors based on array‐sensing technology. Furthermore, the selective adsorption behavior suggests that these ZIF materials have great potentials in the applications of biofuel recovery and the separation of benzene/cyclohexane, xylene, and hexane isomers.     

Stimuli‐Responsive Nucleic Acid‐Based Polyacrylamide Hydrogel‐Coated Metal–Organic Framework Nanoparticles for Controlled Drug Release

The synthesis of doxorubicin‐loaded metal–organic framework nanoparticles (NMOFs) coated with a stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel is described. The formation of the hydrogel is stimulated by the crosslinking of two polyacrylamide chains, P_A and P_B, that are functionalized with two nucleic acid hairpins ( 4 ) and ( 5 ) using the strand‐induced hybridization chain reaction. The resulting duplex‐bridged polyacrylamide hydrogel includes the anti‐ATP (adenosine triphosphate) aptamer sequence in a caged configuration. The drug encapsulated in the NMOFs is locked by the hydrogel coating. In the presence of ATP that is overexpressed in cancer cells, the hydrogel coating is degraded via the formation of the ATP–aptamer complex, resulting in the release of doxorubicin drug. In addition to the introduction of a general means to synthesize drug‐loaded stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel‐coated NMOFs hybrids, the functionalized NMOFs resolve significant limitations associated with the recently reported nucleic acid‐gated drug‐loaded NMOFs. The study reveals substantially higher loading of the drug in the hydrogel‐coated NMOFs as compared to the nucleic acid‐gated NMOFs and overcomes the nonspecific leakage of the drug observed with the nucleic‐acid‐protected NMOFs. The doxorubicin‐loaded, ATP‐responsive, hydrogel‐coated NMOFs reveal selective and effective cytotoxicity toward MDA‐MB‐231 breast cancer cells, as compared to normal MCF‐10A epithelial breast cells.     

Gold Nanoshell Nanomicelles for Potential Magnetic Resonance Imaging,Light‐Triggered Drug Release,and Photothermal Therapy

A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe₃O₄ magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T₂‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.     

Dye Encapsulated Metal‐Organic Framework for Warm‐White LED with High Color‐Rendering Index

A strategy by encapsulating organic dyes into the pores of a luminescent metal‐organic framework (MOF) is developed to achieve white‐light‐emitting phosphor. Both the red‐light emitting dye 4‐(p‐dimethylaminostyryl)‐1‐methylpyridinium ( DSM ) and the green‐light emitting dye acriflavine ( AF ) are encapsulated into a blue‐emitting anionic MOF ZJU‐28 through an ion‐exchange process to yield the MOF?dye composite ZJU‐28?DSM/AF . The emission color of the obtained composite can be easily modulated by simply adjusting the amount and component of dyes. With careful adjustment of the relative concentration of the dyes DSM and AF , the resulting ZJU‐28?DSM/AF (0.02 wt% DSM , 0.06 wt% AF ) exhibits a broadband white emission with ideal CIE coordinates of (0.34, 0.32), high color‐rendering index value of 91, and moderate correlated color temperature value of 5327 K. Such a strategy can be easily expanded to other luminescent MOFs and dyes, thus opening a new perspective for the development of white light emitting materials.     

Silver‐Infused Porphyrinic Metal–Organic Framework: Surface‐Adaptive,On‐Demand Nanoplatform for Synergistic Bacteria Killing and Wound Disinfection

The fabrication of functional nanoplatforms for combating multidrug‐resistant bacteria is of vital importance. Among them, silver nanoparticles (Ag NPs) have shown an antibacterial effect; however, the remainder cores of Ag NPs after use might have a toxic effect on humans. Thus, Ag ions based materials have been fabricated to substitute Ag NPs for antibacterial applications. Nevertheless, the always‐on release state leads to the low biocompatibility, which limits their biomedical applications. In addition, the single effect also restricts their antibacterial ability. Herein, a powerful surface‐adaptive, on‐demand antimicrobial nanoplatform is fabricated by coating hyaluronic acid (HA) on Ag ions loaded photosensitive metal‐organic frameworks to exhibit a strong synergistic effect. The nanoplatform shows good biocompatibility with nontargeted cells, as negatively charged HA can prevent the release of Ag ions. While in the presence of targeted bacteria, the secreted hyaluronidase can degrade HA on the nanoplatform and produce positively charged nanoparticles, which display increased affinity to bacteria and show a strong synergistic antibacterial effect owing to the released Ag ions and generated reactive oxygen species under visible light irradiation. Importantly, due to the outstanding on‐demand antimicrobial performance, the nanoplatform also shows great effects on treating multidrug‐resistant bacteria infected wounds in mice models.     

pH‐Triggered Pinpointed Cascading Charge‐Conversion and Redox‐Controlled Gene Release Design: Modularized Fabrication for Nonviral Gene Transfection

Although pH and reduction responses are widely applied on gene and drug delivery system, the undefined molecule and disconnected response to corresponding transfection barriers still hamper their further application. Here, a multistage‐responsive lipopeptides polycation‐DNA nanoparticles (namely KR‐DC) as gene vector is designed, consisting of three functional modules. It provides the following outstanding “smart” characteristics: i) facile manufacture and ease to adjust ingredients for different conditions, ii) negatively charged surface to remain stable and increase biocompatibility in physiological environment, iii) pH‐triggered cascading charge‐conversion corresponding to tumor extracellular pH and endo/lysosomal pH, iv) the first stage of charge reversal for uptake enhancement at tumor site, v) the second stage of charge conversion for rapid endosomal escape, vi) the third stage of redox degradation aiming at DNA controlled release and nuclear entry, vii) cell‐penetrating peptides mimicking arginine‐rich periphery targeting to membrane penetration capacity improvement, and viii) lipid forming hydrophobic cavity for potential fat‐soluble drug encapsulation. Finally, KR‐DC nanoparticles achieve significantly enhanced in vitro transfection efficiency by almost four orders of magnitude in manual tumor environment with reduced side effects and satisfying gene expression in Hela xenograft tumor model in vivo.     

Near‐Infrared Triggered Release of uPA from Nanospheres for Localized Hyperthermia‐Enhanced Thrombolysis

Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near‐infrared‐triggered, controlled‐release system, using gold@mesoporous silica core–shell nanospheres (Au@MSNs) with phase‐changed material 1‐tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs‐induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia‐enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on‐demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.     

Conductive Metal–Organic Framework Nanowire Array Electrodes for High‐Performance Solid‐State Supercapacitors

The application of conventional metal–organic frameworks (MOFs) as electrode materials in supercapacitors is largely hindered by their conventionally poor electrical conductivity. This study reports the fabrication of conductive MOF nanowire arrays (NWAs) and the application of them as the sole electrode material for solid‐state supercapacitors. By taking advantage of the nanostructure and making full use of the high porosity and excellent conductivity, the MOF NWAs in solid‐state supercapacitor show the highest areal capacitance and best rate performance of all reported MOF materials for supercapacitors, which is even comparable to most carbon materials.