Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the efficient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA‐181b inhibitor (anti‐miR‐181b) is successfully condensed into polyethyleneimine (PEI)‐modified and folate receptor (FR)‐targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti‐miR‐181b/PTPAuNCs nanocomplexes (PTPAuNC‐NPs), which begin with chemical modification of AuNCs with SH‐PEG₅₀₀₀‐folic acid (SH‐PEG₅₀₀₀‐FA) and SH‐PEG₅₀₀₀ through a gold–sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti‐miR‐181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC‐NPs can efficiently deliver anti‐miR‐181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC‐7721 tumor‐bearing nude mice under near‐infrared radiation. All these results suggest that PTPAuNC‐NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.     

Tumor‐Microenvironment‐Activated In Situ Self‐Assembly of Sequentially Responsive Biopolymer for Targeted Photodynamic Therapy

A sequentially responsive photosensitizer‐integrated biopolymer is developed for tumor‐specific photodynamic therapy, which is capable of forming long‐retained aggregates in situ inside tumor tissues. Specifically, the photosensitizer zinc phthalocyanine (ZnPc) is conjugated with polyethylene glycol (PEG) via pH‐labile maleic acid amide linker and then immobilized onto the hyaluronic acid (HA) chain using a redox‐cleavable disulfide linker. The PEG segment can enhance blood circulation of the molecular carrier after intravenous administration and be shed after reaching the acidic tumor microenvironment, allowing the remaining fragment to self‐assemble into large clusters in situ to avoid backward diffusion and improve tumor retention. This process is driven by hydrophobic interactions and does not require additional external actuation. The aggregates are then internalized by the tumor cells via HA‐facilitated endocytosis, and the high glutathione level in tumor cells eventually leads to the intracellular release of ZnPc to facilitate its interaction with the subcellular lipid structures. This tumor‐triggered morphology‐based delivery platform is constructed with clinically tested components and could potentially be applied to other hydrophobic therapeutics.     

Encapsulation of Nanoparticles Using Nitrilotriacetic Acid End‐Functionalized Polystyrenes and Their Application for the Separation of Proteins

The use of nitrilotriacetic acid end‐functionalized polystyrenes (NTA‐PS) as a multifunctional nanocarrier for the aqueous dispersion of CdSe, γ‐Fe₂O₃ and gold nanoparticles (NPs) is described. When the amphiphilic end‐ functionalized polystyrenes and NPs are dissolved together in tetrahydrofuran, the addition of water causes the spontaneous formation of micellar aggregates, resulting in the successful encapsulation and aqueous dispersion of NPs. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), photoluminescence (PL) spectroscopy, and vibrating sample magnetometer (VSM) are used to characterize the structure and properties of the NPs‐containing micellar aggregates (nanocarrier). After complexation of Ni²⁺ with NTA on the surface of the nanocarrier containing γ‐Fe₂O₃, specific binding between Ni‐NTA complex and histidine‐tagged (His‐tagged) proteins enables selective separation of His‐tagged proteins using a magnet.     

A Fluorinated Bola‐Amphiphilic Dendrimer for On‐Demand Delivery of siRNA,via Specific Response to Reactive Oxygen Species

Functional materials capable of responding to stimuli intrinsic to diseases are extremely important for specific drug delivery at the disease site. However, developing on‐demand stimulus‐responsive vectors for targeted delivery is highly challenging. Here, a stimulus‐responsive fluorinated bola‐amphiphilic dendrimer is reported for on‐demand delivery of small interfering RNA (siRNA) in response to the characteristic high level of reactive oxygen species (ROS) in cancer cells. This dendrimer bears a ROS‐sensitive thioacetal in the hydrophobic core and positively charged poly(amidoamine) dendrons at the terminals, capable of interacting and compacting the negatively charged siRNA into nanoparticles to protect the siRNA and promote cellular uptake. The ROS‐sensitive feature of this dendrimer boosts specific and efficient disassembly of the siRNA/vector complexes in ROS‐rich cancer cells for effective siRNA delivery and gene silencing. Moreover, the fluorine tags in the vector enable ¹⁹F‐NMR analysis of the ROS‐responsive delivery process. In addition, this ingenious and distinct bola‐amphiphilic dendrimer is also able to combine the advantageous delivery features of both lipid and dendrimer vectors. Therefore, it represents an innovative on‐demand stimulus‐responsive delivery platform.     

Nucleus‐Targeting Gold Nanoclusters for Simultaneous In Vivo Fluorescence Imaging,Gene Delivery,and NIR‐Light Activated Photodynamic Therapy

The nucleus is one of the most important cellular organelles and molecular anticancer drugs, such as cisplatin and doxorubicin, that target DNA inside the nucleus, are proving to be more effective at killing cancer cells than those targeting at cytoplasm. Nucleus‐targeting nanomaterials are very rare. It is a grand challenge to design highly efficient nucleus‐targeting multifunctional nanomaterials that are able to perform simultaneous bioimaging and therapy for the destruction of cancer cells. Here, unique nucleus‐targeting gold nanoclusters (TAT peptide–Au NCs) are designed to perform simultaneous in vitro and in vivo fluorescence imaging, gene delivery, and near‐infrared (NIR) light activated photodynamic therapy for effective cancer cell killing. Confocal laser scanning microscopy observations reveal that TAT peptide–Au NCs are distributed throughout the cytoplasm region with a significant fraction entering into the nucleus. The TAT peptide–Au NCs can also act as DNA nanocargoes to achieve very high gene transfection efficiencies (≈81%) in HeLa cells and in zebrafish. Furthermore, TAT peptide–Au NCs are also able to sensitize formation of singlet oxygen (¹O₂) without the co‐presence of organic photosensitizers for the destruction of cancer cells upon NIR light photoexcitation.     

Size‐Controlled Synthesis of Cu2‐xE (E = S,Se) Nanocrystals with Strong Tunable Near‐Infrared Localized Surface Plasmon Resonance and High Conductivity in Thin Films

A facile method for preparing highly self‐doped Cu_2‐xE (E = S, Se) nanocrystals (NCs) with controlled size in the range of 2.8–13.5 nm and 7.2–16.5 nm, for Cu_2‐xS and Cu_2‐xSe, respectively, is demonstrated. Strong near‐infrared localized surface plasmon resonance absorption is observed in the NCs, indicating that the as‐prepared particles are heavily p‐doped. The NIR plasmonic absorption is tuned by varying the amount of oleic acid used in synthesis. This effect is attributed to a reduction in the number of free carriers through surface interaction of the deprotonated carboxyl functional group of oleic acid with the NCs. This approach provides a new pathway to control both the size and the cationic deficiency of Cu_2‐xSe and Cu_2‐xS NCs. The high electrical conductivity exhibited by these NPs in metal‐semiconductor‐metal thin film devices shows promise for applications in printable field‐effect transistors and microelectronic devices.     

Gel–Liposome‐Mediated Co‐Delivery of Anticancer Membrane‐Associated Proteins and Small‐Molecule Drugs for Enhanced Therapeutic Efficacy

A programmed drug‐delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core–shell‐based “nanodepot” consisting of a liposomal core and a crosslinked‐gel shell (designated Gelipo) is developed for the sequential and site‐specific delivery (SSSD) of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and doxorubicin (Dox). As a small‐molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half‐maximal inhibitory concentration (IC₅₀) of TRAIL and Dox co‐loaded Gelipo (TRAIL/Dox‐Gelipo) toward human breast cancer (MDA‐MB‐231) cells is 83 ng mL^–1 (Dox concentration), which presents a 5.9‐fold increase in the cytotoxicity compared to 569 ng mL^–1 of Dox‐loaded Gelipo (Dox‐Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA‐MB‐231 xenograft tumor animal model.     

An O2 Self‐Sufficient Biomimetic Nanoplatform for Highly Specific and Efficient Photodynamic Therapy

Conventional oxygen‐dependent photodynamic therapy (PDT) has faced severe challenges because of the non‐specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. Here, an O₂ self‐sufficient cell‐like biomimetic nanoplatform (CAT‐PS‐ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton‐like porous zeolitic imidazolate framework (ZIF‐8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS₄, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT‐PS‐ZIF@Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H₂O₂ penetration into the framework, it is catalyzed by CAT to produce O₂ at the hypoxic tumor site, facilitating the generation of toxic ¹O₂ for highly effective PDT in vivo under near‐infrared irradiation. By integrating the immune escape, cell homologous recognition, and O₂ self‐sufficiency, this cell‐like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side‐effect on normal tissues.     

Dual Acid‐Responsive Micelle‐Forming Anticancer Polymers as New Anticancer Therapeutics

Cinnamaldehyde, a major active compound of cinnamon, is known to induce apoptotic cell death in numerous human cancer cells. Here, dual acid‐responsive polymeric micelle‐forming cinnamaldehyde prodrugs, poly[(3‐phenylprop‐2‐ene‐1,1‐diyl)bis(oxy)bis(ethane‐2,1‐diyl)diacrylate]‐co‐4,4’(trimethylene dipiperidine)‐co‐poly(ethylene glycol), termed PCAE copolymers, are reported. PCAE is designed to incorporate cinnamaldehyde via acid‐cleavable acetal linkages in its pH‐sensitive hydrophobic backbone and self assemble to form stable micelles which can encapsulate camptothecin (CPT). PCAE self assembles to form micelles which release CPT and cinnamaldehyde in pH‐dependent manners. PCAE micelles induce apoptotic cell death through the generation of intracellular reactive oxygen species (ROS) and exert synergistic anticancer effects with a payload of CPT in vitro and in vivo model of SW620 human colon tumor‐bearing mice. It is anticipated that dual acid‐sensitive micelle‐forming PCAE with intrinsic anticancer activities has enormous potential as novel anticancer therapeutics.     

Ultrasmall CuCo2S4 Nanocrystals: All‐in‐One Theragnosis Nanoplatform with Magnetic Resonance/Near‐Infrared Imaging for Efficiently Photothermal Therapy of Tumors

Copper‐based ternary bimetal chalcogenides have very promising potential as multifunctional theragnosis nanoplatform for photothermal treatment of tumors. However, the design and synthesis of such an effective platform remains challenging. In this study, hydrophilic CuCo₂S₄ nanocrystals (NCs) with a desirable size of ≈10 nm are synthesized by a simple one‐pot hydrothermal route. The as‐prepared ultrasmall CuCo₂S₄ NCs show: 1) intense near‐infrared absorption, which is attributed to 3d electronic transitions from the valence band to an intermediate band, as identified by density functional theory calculations; 2) high photothermal performance with a photothermal conversion efficiency up to 73.4%; and 3) capability for magnetic resonance (MR) imaging, as a result of the unpaired 3d electrons of cobalt. Finally, it is demonstrated that the CuCo₂S₄ NCs are a promising “all‐in‐one” photothermal theragnosis nanoplatform for photothermal cancer therapy under the irradiation of a 915 nm laser at a safe power density of 0.5 W cm^?2, guided by MR and infrared thermal imaging. This work further promotes the potential applications of ternary bimetal chalcogenides for photothermal theragnosis therapy.     

Dual‐Stage‐Light‐Guided Tumor Inhibition by Mitochondria‐Targeted Photodynamic Therapy

In this paper, a self‐delivery system PpIX‐PEG‐(KLAKLAK)₂ (designated as PPK) is fabricated to realize mitochondria‐targeted photodynamic tumor therapy. It is found that the PPK self‐delivery system exhibited high drug loading efficacy as well as novel capacity in generation of intracellular reactive oxygen species (ROS). This study also indicated that the photochemical internalization effect of the photosensitizer protoporphyrin IX (PpIX) under a short time light irradiation improved the cellular internalization of PPK. On the contrary, PPK could target to the subcellular organelle mitochondria due to the presence of proapoptosis (KLAKLAK)₂ peptide. Importantly, the in situ generation of ROS in mitochondria enhanced the photodynamic therapy efficacy under another long time irradiation, leading to significant cell death with decreased mitochondrial membrane potential. Besides, relative high tumor accumulation, minimal systemic cytotoxicity and efficacious long‐term tumor inhibition in vivo are also confirmed by using a murine model. All these results demonstrated the self‐delivery system PPK with a dual‐stage light irradiation strategy is a promising nanoplatform for tumor treatment.     

Chitosan–Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM‐1‐Targeting Nanocarriers,Enabling GI Targeting In Vivo

When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve NC oral delivery to treat gastrointestinal (GI) pathologies or for systemic absorption. However, GI instability of targeting moieties compromises this strategy. This study explores whether encapsulation of antibody‐coated NCs in microcapsules would protect against gastric degradation, providing NC release and targeting in intestinal conditions. Nanoparticles coated with antibodies against intercellular adhesion molecule‐1 (anti‐ICAM) or nonspecific immunoglobulin G (IgG) are encapsulated in chitosan (shell) ‐ alginate (core) microcapsules. Encapsulation efficiency is >95% and NC relase from microcapsules in storage is <10%. There is minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75%–85%). Encapsulated NCs afford increased protection against degradation (threefold to fourfold) and increased cell targeting (8–20‐fold) after release versus the nonencapsulated NCs. Mouse oral gavage shows that microencapsulation provides 38%–65% greater protection of anti‐ICAM NCs in the GI tract, 40% lower gastric retention, and fourfold to ninefold enhanced intestinal biodistribution versus nonencapsulated NCs. Therefore, microencapsulation of antibody‐targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery.     

Multifunctional Graphene Oxide‐based Triple Stimuli‐Responsive Nanotheranostics

Construction of multifunctional stimuli‐responsive nanosystems intelligently responsive to inner physiological and/or external irradiations based on nanobiotechnology can enable the on‐demand drug release and improved diagnostic imaging to mitigate the side‐effects of anticancer drugs and enhance the diagnostic/therapeutic outcome simultaneously. Here, a triple‐functional stimuli‐responsive nanosystem based on the co‐integration of superparamagnetic Fe₃O₄ and paramagnetic MnO_x nanoparticles (NPs) onto exfoliated graphene oxide (GO) nanosheets by a novel and efficient double redox strategy (DRS) is reported. Aromatic anticancer drug molecules can interact with GO nanosheets through supramolecular π stacking to achieve high drug loading capacity and pH‐responsive drug releasing performance. The integrated MnO_x NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH‐responsive and reduction‐triggered T₁‐weighted magnetic resonance imaging (MRI). Superparamagnetic Fe₃O₄ NPs can not only function as the T₂‐weighted contrast agents for MRI, but also response to the external magnetic field for magnetic hyperthermia against cancer. Importantly, the constructed biocompatible GO‐based nanoplatform can inhibit the metastasis of cancer cells by downregulating the expression of metastasis‐related proteins, and anticancer drug‐loaded carrier can significantly reverse the multidrug resistance (MDR) of cancer cells.     

Injectable Polypeptide‐Protein Hydrogels for Promoting Infected Wound Healing

Protein is the key composition of all tissues, which has also been widely used in tissue engineering due to its superior biocompatibility and low immunogenicity. However, natural protein usually lacks active functions such as vascularization, osteo‐induction, and neural differentiation, which limits its further applications as a functional biomaterial. Here, based on the mimetic extracellular matrix feature of bovine serum albumin, injectable polypeptide‐protein hydrogels with vascularization and antibacterial abilities are constructed successfully via coordinative cross‐linking of sulfydryl groups with silver ions (Ag+) for the regeneration of infected wound. In this protein hydrogel system, (Ag+), acting as crosslinkers, can not only provide a sterile microenvironment and a strong and robust antibacterial ability but also introduce K₂(SL)₆K₂ (KK) polypeptide, which endows the hydrogel with vascularization behavior. Furthermore, the in vivo data show that the polypeptide‐protein hydrogel has a considerable collagen deposition and vascularization abilities in the early stage of wound healing, resulting in rapid new tissue regeneration featured with newly appeared hair follicles. Altogether, this newly developed multifunctional 3D polypeptide‐protein hydrogel with vascularization, antibacterial properties, and hair follicle promotion can be a promising approach in biomedical fields such as infected wound healing.     

Evidence for the Band‐Edge Exciton of CuInS2 Nanocrystals Enables Record Efficient Large‐Area Luminescent Solar Concentrators

Ternary I‐III‐VI₂ nanocrystals (NCs), such as CuInS₂, are receiving attention as heavy‐metals‐free materials for solar cells, luminescent solar concentrators (LSCs), LEDs, and bio‐imaging. The origin of the optical properties of CuInS₂ NCs are however not fully understood. A recent theoretical model suggests that their characteristic Stokes‐shifted and long‐lived luminescence arises from the structure of the valence band (VB) and predicts distinctive optical behaviours in defect‐free NCs: the quadratic dependence of the radiative decay rate and the Stokes shift on the NC radius. If confirmed, this would have crucial implications for LSCs as the solar spectral coverage ensured by low‐bandgap NCs would be accompanied by increased re‐absorption losses. Here, by studying stoichiometric CuInS₂ NCs, it is revealed for the first time the spectroscopic signatures predicted for the free band‐edge exciton, thus supporting the VB‐structure model. At very low temperatures, the NCs also show dark‐state emission likely originating from enhanced electron‐hole spin interaction. The impact of the observed optical behaviours on LSCs is evaluated by Monte Carlo ray‐tracing simulations. Based on the emerging device design guidelines, optical‐grade large‐area (30×30 cm²) LSCs with optical power efficiency (OPE) as high as 6.8% are fabricated, corresponding to the highest value reported to date for large‐area devices.     

Tumor‐Specific Self‐Degradable Nanogels as Potential Carriers for Systemic Delivery of Anticancer Proteins

Development of a safe and effective carrier for systemic protein delivery is highly desirable, which depends on management of the relationship among loading capacity, stability, delivery efficiency, and degradability. Here, a tumor‐specific self‐degradable nanogel composed of hyaluronidase (HAase)‐degradable hyaluronic acid (HA) matrices entrapping acid‐activatable HAase (aHAase) for systemic delivery of anticancer proteins is reported. Collaboratively crosslinked nanogels (cNG) obtained by the synthetic cholesteryl methacrylated HA show high protein‐loading capacity and stability. The aHAase is engineered by modifying the HAase with citraconic anhydride to shield its HA‐degrading activity, which can be reversibly activated by hydrolysis of the citraconic amide under acidic condition. In the tumor microenvironment, the mild acidity activates the aHAase partially, which results in swelling of the cNG and releasing of the aHAase. The released reactivated aHAase can degrade the HA that is also a major constituent of tumor extracellular matrix to increase perfusion of the cNG in the tumor stroma. In the acidic endocytic vesicles, the aHAase is fully reactivated. The active aHAase completely degrades the cNG to release the encapsulated anticancer protein, deoxyribonuclease I intracellularly, which digests the DNA to cause tumor cell death for enhanced antitumor efficacy.     

Localization of Au Nanoclusters on Layered Double Hydroxides Nanosheets: Confinement‐Induced Emission Enhancement and Temperature‐Responsive Luminescence

Gold nanoclusters (Au NCs) stand for a new type of fluorescent nanomaterials with outstanding optical properties due to their discrete electronic energy and direct electron transition. However, relative low quantum yield (QY) of Au NCs in aqueous or solid state has limited their photofunctional applications. To improve the fluorescent performances of Au NCs and find an effective approach for the fabrication of Au NCs‐based films, in this work, Au NCs are localized onto 2D layered double hydroxides (LDHs) nanosheets via a layer‐by‐layer assembly process; the as‐fabricated (Au NCs/LDH)_n ultrathin films (UTFs) show an ordered and dense immobilization of Au NCs. The localization and confinement effects imposed by LDH nanosheets induce significantly increased emissive Au(I) units as confirmed by X‐ray photoelectron spectroscopy and periodic density functional theoretical simulation, which further results in promoted QY (from 2.69% to 14.11%) and prolonged fluorescence lifetime (from 1.84 µs to 14.67 µs). Moreover, the ordered (Au NCs/LDH)_n UTFs exhibit well‐defined temperature‐dependent photoluminescence (PL) and electrochemiluminescence (ECL) responses. Therefore, this work supplies a facile strategy to achieve the immobilization of Au NCs and obtain Au NCs‐based thin films with high luminescent properties, which have potential applications in PL and ECL temperature sensors.     

Tuning the Microenvironment: Click‐Crosslinked Hyaluronic Acid‐Based Hydrogels Provide a Platform for Studying Breast Cancer Cell Invasion

A big challenge in cell culture is the non‐natural environment in which cells are routinely screened, making in vivo phenomena, such as cell invasion, difficult to understand and predict. To study cancer cell invasion, extracellular matrix (ECM) analogs with decoupled mechanical and chemical properties are required. Hyaluronic acid (HA)‐based hydrogels crosslinked with matrix‐metalloproteinase (MMP)‐cleavable peptides are developed to study MDA‐MB‐231 breast cancer cell invasion. Hydrogels are synthesized by reacting furan‐modified HA with bismaleimide peptide crosslinkers in a Diels–Alder click reaction. This new hydrogel takes advantage of the biomimetic properties of HA, which is overexpressed in breast cancer, and eliminates the use of nonadhesive crosslinkers, such as poly(ethylene glycol) (PEG). The crosslink (mechanical) and ligand (chemical) densities are varied independently to evaluate the effects of each parameter on cell migration. Increased crosslink density correlates with decreased MDA‐MB‐231 cell invasion whereas incorporation of MMP‐cleavable sequences within the peptide crosslinker enhances invasion. Increasing the ligand density of pendant GRGDS groups induces cell proliferation, but has no significant impact on invasion. By independently tuning the mechanical and chemical environment of ECM mimetic hydrogels, a platform is provided that recapitulates variable tissue properties and elucidates the role of the microenvironment in cancer cell invasion.     

UV‐Light‐Driven Immobilization of Surface‐Functionalized Oxide Nanocrystals onto Silicon

TiO₂ nanorods (NRs) and γ‐Fe₂O₃ nanocrystals (NCs) passivated with unsaturated long‐chain carboxylic acids, namely 10‐undecylenic acid (10UDA) and oleic acid (OLEA), are covalently anchored to Si(100) at room temperature by UV‐light‐driven reaction of hydrogenated silicon with the carbon–carbon double bond (–C?C–) moieties of the capping surfactants. The high reactivity of vinyl groups towards Si provides a general tool for attaching particles of both materials via Si–C bonds. Interestingly, TiO₂ NRs were efficiently attached to silicon even when capped by OLEA. This latter finding has been explained by a photocatalytic mechanism involving the primary role of hydroxyl radicals that can be generated upon bandgap TiO₂ photoexcitation with UV light. The increased oxide coverage achievable on Si opens access to further surface manipulation, as demonstrated by the possibility of depositing an additional film of Au nanoparticles onto TiO₂ via TiO₂‐catalyzed visible‐light‐driven reduction of aqueous AuCl₄^– ions. Extensive morphological and chemical characterization of the obtained NC‐functionalized Si substrates is provided to support the effectiveness of proposed photochemical approaches.     

In Situ Polymerized Hollow Mesoporous Organosilica Biocatalysis Nanoreactor for Enhancing ROS‐Mediated Anticancer Therapy

The combination of reactive oxygen species (ROS)‐involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhancing ROS‐mediated cancer treatment. Herein, an in situ polymerized hollow mesoporous organosilica nanoparticle (HMON) biocatalysis nanoreactor is reported to integrate the synergistic effect of PDT/CDT for enhancing ROS‐mediated pancreatic ductal adenocarcinoma treatment. 2‐(1‐hexyloxyethyl)‐2‐devinylpyropheophorbide‐a photosensitizer is hybridized within the framework of HMON via an “in situ framework growth” approach. Then, the hollow cavity of HMONs is exploited as a nanoreactor for “in situ polymerization” to synthesize the polymer containing thiol groups, thereby enabling the immobilization of ultrasmall gold nanoparticles, which behave like glucose oxidase‐like nanozyme, converting glucose into H₂O₂ to provide self‐supplied H₂O₂ for CDT. Meanwhile, Cu²⁺‐tannic acid complexes are further deposited on the surface of HMONs (HMON‐Au@Cu‐TA) to initiate Fenton‐like reaction to covert the self‐supplied H₂O₂ into ?OH, a highly toxic ROS. Finally, collagenase (Col), which can degrade the collagen I fiber in the extracellular matrix, is loaded into HMON‐Au@Cu‐TA to enhance the penetration of HMONs and O₂ infiltration for enhanced PDT. This study provides a good paradigm for enhancing ROS‐mediated antitumor efficacy. Meanwhile, this research offers a new method to broaden the application of silica based nanotheranostics.