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Fluorescein angiography (FA) is a standard imaging modality for evaluating vascular abnormalities in retina-related diseases, which is recognized as the major cause of vision loss. Long-term and real-time fundus angiography is of great importance in preclinical research, nevertheless remaining big challenges up to present. In this study, we demonstrate that long-term fluorescence imaging of retinal vessels is enabled through a kind of fluorescent nanoagents, which is made of small-sized (hydrodynamic diameter: ∼ 3 nm) silicon nanoparticles (SiNPs) featuring strong fluorescence, robust photostability, lengthened blood residency and negligible toxicity. In particular, the presented SiNPs-based nanoagents are capable of imaging retinal capillaries in ∼ 10 min, which is around 10-fold longer than that (∼ 1 min) of fluorescein sodium (FS, known as the most widely used contrast agents for FA in clinic). Taking cynomolgus macaques as non-human primate-animal model, we further demonstrate the feasibility of real-time diagnosis of retinal diseases (e.g., age-related macular degeneration (AMD)) through dynamic monitoring of vascular dysfunction.

A piezo-photocatalytic therapy based on thermally treated natural sphalerite nanosheet (NSH700 NS) heterojunction was applied to efficiently induce intracellular ROS burst and apoptosis of cancer cells. Upon ultrasound and laser irradiation, the formation of a polarized electric field and band bending of NSH700 NSs allow the directional separation of charges both in the bulk and their interface, thereby minimizing the probability of charge recombination. The piezo-photocatalytic effect leads to an efficient catalytic performance, exhibiting high-performance superoxide radical (˙O2−) and hydroxyl radical (˙OH) generation and glutathione (GSH) depletion, which results in a intracellular ROS burst-triggered apoptosis of cancer cells both in vitro and in vivo.

Recommended as a medical emergency, infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness. Herein, we present a kind of theranostic agents, which are made of vancomycin (Van)-modified fluorescent silicon nanoparticles (SiNPs-Van), enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner. Typically, the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro (5 min) and in vivo (10 min), making them an efficacious diagnostic agent for the detection of bacterial keratitis. In addition, the SiNPs-Van feature distinct antimicrobial activity, with superior activity of 92.5% at a concentration of 0.5 µg/mL against Staphylococcus aureus (S. aureus); comparatively, the antimicrobial rate of free vancomycin is 23.3% at the same concentration. We further explore the SiNPs-Van agents as eye drops for therapy of S. aureus-induced bacterial keratitis on rat model. Represented by slit-lamp scores, the keratitis severity of SiNPs-Van-treated corneas is 3.4, which is 59.6% and 77.3% slighter than vancomycin- (8.2 score) and PBS-treated corneas (15.0 score), respectively. The infected corneas recover to normal (1 score) after 7-d of SiNPs-Van treatment. Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents, especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.

Developing a biocatalyzed artificial photosynthesis system (APS) with a Z-scheme for CO2 conversion has a promising outlook. However, it remains unexplored and challenging. Herein, we present an antimonene (AM) and black phosphorus (BP) hybrid nanosheet (HNSs) based Z-scheme APS for enhanced photo/bio-catalytic CO2 reduction. An “amphipathic” polymer PEI-PEG-C18 with a positively charged PEI-head and hydrophobic C18-tail was synthesized and further modified with an electron mediator (M, Cp*Rh(phen)Cl). Using this PEI-PEG-C18-M as a “double-side tap”, AM/M/BP HNS-based Z-scheme photocatalytic systems were constructed through catenating AM NSs via a hydrophobic interaction with the hydrophobic C18-tail and subsequent BP NSs via electrostatic interactions with the positively charged PEI-head. Thereafter, the biocatalytic system, including NAD(H)+ and redox enzymes, were sandwiched between the AM and BP layers through an electrostatic attraction with the amide groups in the “double-side tap”. Due to the high separation efficiency of the photogenerated electrons and holes and the improved reduction and oxidation potentials, the integrated Z-scheme APS shows excellent performance. In particular, although neither AM nor BP could catalyze NADH regeneration using H2O as an electron donor under visible light, a 35 ± 4% regeneration of NADH and 160 ± 24 μmol formic acid production were achieved by the AM/M/BP HNS-based Z-scheme APS. Moreover, the compatibility and omnipotence of the HNS-based APS for the synthesis of other high value-added products from CO2 have been demonstrated through assembling the corresponding biocatalysts.

Neighboring carbon and sandwiched between non‐metals and metals in the periodic table of the elements, boron is one of the most chemically and physically versatile elements, and can be manipulated to form dimensionally low planar structures (borophene) with intriguing properties. Herein, the theoretical research and experimental developments in the synthesis of borophene, as well as its excellent properties and application in many fields, are reviewed. The decade‐long effort toward understanding the size‐dependent structures of boron clusters and the theory‐directed synthesis of borophene, including bottom‐up approaches based on different foundations, as well as up‐down approaches with different exfoliation modes, and the key factors influencing the synthetic effects, are comprehensively summarized. Owing to its excellent chemical, electronic, mechanical, and thermal properties, borophene has shown great promise in supercapacitor, battery, hydrogen‐storage, and biomedical applications. Furthermore, borophene nanoplatforms used in various biomedical applications, such as bioimaging, drug delivery, and photonic therapy, are highlighted. Finally, research progress, challenges, and perspectives for the future development of borophene in large‐scale production and other prospective applications are discussed., The successful theoretical‐research‐guided synthesis of borophene marks a milestone for the synthesis of 2D materials without layered bulk structures. The excellent properties and wide applications of borophene make it a new cousin of graphene in the family of 2D materials.

Two-dimensional (2D) nanosheet (NS)-based photothermal agents (PTAs), such as transition-metal dichalcogenides, have shown immense potential for their use in cancer photothermal therapy (PTT). However, the nano-bio interaction study regarding these NS-based PTAs is still in its infancy. In this study, we used WS2-PEG NS-based PTA as an example to provide comprehensive insights into the experimental understanding of their fate in cancer cells. The data revealed that three different endocytosis pathways (macropinocytosis, clathrin-dependent, and caveolae-dependent endocytosis), autophagy-mediated lysosome accumulation, and exocytosis-induced excretion contribute to the integrated pathways of WS2-PEG NSs within cells. These pathways are consistent with our previous reports on MoS2-PEG NS-based drug delivery platform, indicating that the composition difference of 2D NSs with PEGylation may have little influence on their intercellular fate. Moreover, by blocking the revealed exocytosis pathway-mediated secretion of WS2 NSs in tumor cells, an effective approach is proposed to attain enhanced photothermal therapeutic outcomes with low doses of WS2 NSs and under a low power of a near-infrared (NIR) laser. We expect that the exocytosis inhibition strategy may be a universal one for 2D NSs to achieve combination cancer therapy. This study may also provide more experimental basis for the future development of 2D NS’s application in biomedicine (e.g. PTT).

The emergence of novel two-dimensional (2D) monoelemental materials (Xenes) has shown remarkable potential for their applications in different fields of technology, as well as addressing new discoveries in fundamental science. Xenes (e.g., borophene, silicene, germanene, stanene, phosphorene, arsenene, antimonene, bismuthene, and tellurene) are of particular interest because they are the most chemically tractable materials for synthetic exploration. Owing to their excellent physical, chemical, electronic and optical properties, Xenes have been regarded as promising agents for biosensors, bioimaging, therapeutic delivery, and theranostics, as well as in several other new bio-applications. In this tutorial review, we summarize their general properties including the classification of Xenes according to their bulk properties. The synthetic and modification methods of Xenes are also presented. Furthermore, the representative Xene nanoplatforms for various biomedical applications are highlighted. Finally, research progress, challenges, and perspectives for the future development of Xenes in biomedicines are discussed.

The induced expansion of tumor-initiating cells (T-ICs) upon repeated exposure of tumors to chemotherapeutic drugs forms a major cause for chemoresistance and cancer metastasis. Here, a tumor-microenvironment-responsive hydrogel patch is designed to modulate the plasticity of T-ICs in triple-negative breast cancer (TNBC), which is insensitive to hormone- and HER2-targeting. The on-site formation of the hydrogel network patches tumors in a chemoresistant TNBC murine model and senses intratumoral reactive oxygen species for linker cleavage and payload release. Patch-mediated inhibition of the histone demethylase lysine-specific demethylase 1 (LSD1) epigenetically regulates the switch of T-ICs from self-renewal to differentiation, rehabilitating their chemosensitivity. Moreover, the hydrogel patch enhances tumor immunogenicity and increases T-cell infiltration via epigenetic activation of innate immunity. A single-dose of the hydrogel patch harboring LSD1 inhibitor and chemotherapy agent efficiently suppresses tumor growth, postsurgical relapse, and metastasis. The superior efficacy against multidrug resistance further reveals the broad applicability of epigenetic remodeling hydrogel patches.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non-invasiveness and high tissue-penetrating depth. However, developing biocompatible nanomaterial-based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid-phase exfoliation strategy to obtain a new type of two-dimensional (2D) stanene-based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano-sonosensitizers, allowing a more efficient US-triggered separation of electron (e- )-hole (h+ ) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near-infrared (NIR)-mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug delivery owing to the inherent 2D layered structure. This study not only presents general nanoplatforms for SDT-enhanced combination cancer therapy, but also highlights the utility of 2D SnNSs to the field of nanomedicine.

Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe2O3) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs., Clay-based nanomaterials are of wide interest but problems extracting the 2D functional core layers have limited potential applications. Here, the authors report on the wet exfoliation of vermiculite by alkali etching to obtain the core layers and explore the application of the materials in cancer theranostics.

The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu2+-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu2+ into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing 64Cu2+, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an “ideal” PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy., A balance between high stability and rapid degradation is required for effective photothermal anti-cancer agents. Here, the authors use Cu2+ to accelerate the degradation of black phosphorus nanosheets while enhancing its photothermal ability and apply this material for PET-guided, CDT-enhanced combination cancer therapy in mice.

Combination therapies for cancer have been promising strategies to reverse multidrug resistance, improve treatment efficiency, and minimize side effects. Herein, a new type of multifunctional silicon nanowire (MFSiNW)-based system, i.e., iron oxide nanoparticle and gold nanoparticle decorated silicon nanowires (IONPs@AuNPs@SiNWs), is prepared through a facile synthetic strategy. The resultant nanohybrids could load therapeutic drug molecules (e.g., doxorubicin, DOX) with high drug loading capacity (2000 mg g−1), and be simultaneously responsive to pH/NIR (near-infrared) light/magnetism, thus enabling high-efficacy synergistic treatment of drug-resistant cancer cells. The current work provides the pioneering demonstration of silicon nanomaterial-based combinational cancer treatment with high therapeutic efficiency.

The direct connection between a photosensitizer and an electron mediator, achieved by a precise arrangement based on chlorosome, provides photosynthetic bacteria the maximum efficiency in solar energy conversion. Herein, this study reports the fabrication of a biomimicking chlorosome for biocatalyzed artificial photosynthesis through self-assembly of simple molecules to functional systems. TCPP/EYx/Rh8–x macromolecules, synthesized through a sequential amidation reaction of porphyrin (TCPP), eosin Y (EY), and [Cp*RhCl2]2, were found to self-assemble into chlorosome-mimicking supramolecular assemblies through noncovalent interactions. Intra- and intermolecular dual channels for enhancing electron transfer were constructed in TCPP/EYx/Rh8–x supramolecular assemblies. In addition, the energy band structure of TCPP/EY4/Rh4 supramolecular assemblies also made a perfect coordination with oxidation and reduction potentials of an electron donor and NAD+, which led to a fast and oriented electron transfer along th...

Ocular neovascularization can result in devastating diseases that lead to marked vision impairment and eventual visual loss. In clinical implementation, neovascular eye diseases are first diagnosed by fluorescein angiography and then treated by multiple intravitreal injections, which nevertheless involves vision-threatening complications, as well as lack of real-time monitoring disease progression and timely assessment of therapeutic outcomes. To address this critical issue, we herein present a kind of theranostic agents made of peptide-functionalized silicon nanoparticles (SiNPs), suitable for simultaneous ocular neovascularization imaging and therapy. Typically, in addition to negligible toxicity and high specific binding ability to human retinal microvascular endothelial cells tube formation, the cyclo-(Arg-Gly-Asp-d-Tyr-Cys) ( c-(RGDyC))-conjugated SiNPs (SiNPs-RGD) features efficacious antiangiogenic ability in wound healing migration, transwell migration, transwell invasion, and tube formation assays. Taking advantage of these unique merits, we further employ the SiNPs-RGD for labeling angiogenic blood vessels and neovascularization suppression, demonstrating obvious inhibition of new blood vessels formation in mouse corneas. These results suggest the SiNPs-RGD as a novel class of high-quality theranostic probes is suitable for simultaneous diagnosis and treatment in ocular neovascular diseases.

Based on the unique advantages of fluorescent silicon nanoparticles (SiNPs), long circulation red blood cells (RBCs), and anti-cancer drug molecules (i.e., doxorubicin (DOX)), we developed multifunctional DOX-loaded SiNPs impregnated into RBCs. Importantly, the resulting drug delivery systems (DDSs) simultaneously exhibited bright fluorescence coupled with robust photostability (i.e., ∼ 24% loss of fluorescent intensity after 25 min continuous laser irradiation) and significantly lengthened blood residency (i.e., t1/2 = 7.31 ± 0.96 h, 3.9-fold longer than pure DOX-loaded SiNPs). Therefore, this novel DDS featuring multi-functionalities shows high potential for cancer diagnosis and therapy, particularly for tumor imaging and chemotherapy in a synchronous manner.

Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (i.e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS2 NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS2 NSs. Ba...

A novel photocatalyst/biocatalyst integrated artificial photosynthesis system (APS) based on polyurethane hollow nanofibers doped with graphene oxide (GO) and poly(allylamine hydrochloride) (PAH) was developed and employed for selective methanol conversion from CO2. The biocatalysts, including formate, formaldehyde, and alcohol dehydrogenases, as well as NAD+, were in situ coencapsulated inside the lumen of the GO-PAH-doped PU nanofibers (G-Fiber) by simply predissolving them in the core-phase solution for coaxial electrospinning, while the precise assembling of the photocatalyst parts involving visible light active photosensitizer (PS) and electron mediator (M) on the surface of the G-Fiber was realized by their π–π interactions with the GO doped in the shell of fibers. By using this highly integrated APS, about 10-times higher methanol yield was accomplished as compared with the solution-based system. The significantly enhanced reaction efficiency of the G-Fiber-based APS is considered predominately due...

The development of biocompatible and fluorescent gene carriers is of particular importance in the gene-delivery field. Taking advantage of the unique optical properties (e.g., strong and robust fluorescence) of silicon nanoparticles (SiNPs), as well as the excellent biocompatibility of silicon and protamine sulfate (PS, approved by the U.S. Food and Drug Administration (FDA) for clinical use), we herein present a type of PS-modified SiNP (PS@SiNP)-based gene carrier. Plasmid DNA (pDNA) with negative charges can be effectively bound onto the surface of the as-prepared fluorescent PS@SiNP-based gene carriers via electrostatic interactions. In particular, such resultant gene carriers possess stable and high fluorescence (photoluminescent quantum yield (PLQY): ∼25%). In addition, the PS@SiNP-based gene carriers show minimal toxic effects on normal mitochondrial metabolic activity (e.g., human retinal pigment epithelial (ARPE-19) cells preserve ∼90% of their cell viability after a 48 h incubation with the resultant carriers). Based on tracking the strong and stable fluorescence signals of SiNPs, the dynamic behavior of the PS@SiNP-based gene carriers in live cells (e.g., clathrin-mediated endocytosis, lysosomal escape, pDNA release, etc.) is investigated in a long-term manner, providing valuable information for understanding the intracellular behavior of gene vectors and designing high-efficacy gene carriers.

A heterogeneous WS2/g-C3N4 composite photocatalyst was prepared by a facile ultrasound-assisted hydrothermal method. The WS2/g-C3N4 composite was used for photocatalytic regeneration of NAD+ to NADH, which were coupled with dehydrogenases for sustainable bioconversion of CO2 to methanol under visible light irradiation. Compared with pristine g-C3N4 and the physical mixture of WS2 and g-C3N4, the fabricated WS2/g-C3N4 composite catalyst with 5 wt% of WS2 showed the highest activity for methanol synthesis. The methanol productivity reached 372.1 μmol h−1 gcat−1, which is approximately 7.5 times higher than that obtained using pure g-C3N4. For further application demonstration, the activity of the WS2/g-C3N4 composite catalyst toward photodegradation of Rhodamine B (RhB) was evaluated. RhB removal ratio approaching 100% was achieved in 1 hour by using the WS2/g-C3N4 composite catalyst with 5 wt% of WS2, at an apparent degradation rate approximately 2.6 times higher than that of pure g-C3N4. Based on detailed investigations on physiochemical properties of the photocatalysts, the significantly enhanced reaction efficiency of the WS2/g-C3N4 composite was considered to be mainly benefiting from the formation of a heterojunction interface between WS2 and g-C3N4. Upon visible-light irradiation, the photo-induced electrons can transfer from the conduction band of g-C3N4 to WS2, thus recombination of electrons and holes was decreased and the photo-harvesting efficiency was enhanced.

Innate sensing of viral RNA analogs represents a promising tool for cancer intervention, yet the tumor microenvironment (TME) renders tumor cells and immune cells unresponsive to exogenous innate stimuli. Herein, we design a hybrid RNA yielding both endogenous retrovirus and exogenous viral signature for orchestrated immune activation. Additionally, we encapsulate the RNA in a TME-responsive nanobooster, which generates oxygen to awaken hypoxia-mediated dormancy of viral RNA sensors. This two-in-one viral mimicry demonstrates synergistic effects on the production of type I interferons (α and β), maturation of dendritic cells and apoptosis of cancer cells, and further stimulates anti-tumor T cell immunity and memory. Significantly, monotherapy with the viral mimicry potently suppresses tumor growth, post-surgical relapse and metastasis in murine liver and breast cancer models, and exhibits long-term resistance against tumor re-challenge. Our study thus provides a straightforward but effective strategy for self-amplification of innate immunity in cancer therapy.

Long-term and real-time investigation of the dynamic process of pHi changes is critically significant for understanding the related pathogenesis of diseases and the design of intracellular drug delivery systems. Herein, we present a one-step synthetic strategy to construct ratiometric pH sensors, which are made of europium (Eu)-doped one-dimensional silicon nanorods (Eu@SiNRs). The as-prepared Eu@SiNRs have distinct emission maxima peaks at 470 and 620 nm under 405 nm excitation. Of particular note, the fluorescence emission intensity at 470 nm decreases along with the increase of pH, while the one at 620 nm is nearly unaffected by pH changes, making Eu@SiNRs a feasible probe for pH sensing ratiometrically. Moreover, Eu@SiNRs are found to be responsive to a broad pH range (ca. 3–9), biocompatible (e.g., ∼100% of cell viability during 24 h treatment) and photostable (e.g., ∼10% loss of intensity after 40 min continuous UV irradiation). Taking advantages of these merits, we employ Eu@SiNRs for the visualiza...

Nanofibrous membranes have been adopted as enzyme carriers via surface adsorption, covalent cross-linking, and direct electrospinning-embedment showing great advantages and successes over other nanostructured materials, and especially the newly developed hollow nanofibers were proven as an ideal scaffold for through in-situ encapsulation of multiple enzymes during co-axial electrospinning. Here, the coaxial electrospinning-encapsulation method based on hollow nanofiber structures, together with three previous strategies, which are all based on solid-structured nanofibers, were adopted to immobilize α-chymotrypsin (CT). The feasibilities and advantages of hollow nanofibers encapsulated enzyme are fully demonstrated by the catalytic kinetics of the immobilized CT for hydrolysis and transesterification. Compared to a solid nanofibers-based enzyme, the hollow nanofibers encapsulated CT show the highest catalytic efficiency for both hydrolysis and transesterification. Besides, the confinement effect provided by the nano-scaled hollow chamber not only facilitated molecular interactions between enzymes and substrates, but also enhanced the enzymes stability largely.

Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for treating a myriad of important diseases through scavenging excessive reactive oxygen and nitrogen species (RONS), a mechanism critical in disease development and progression. However, similar to antioxidative enzymes, currently studied nano-antioxidants have demonstrated scavenging activity to specific RONS, and sufficient antioxidative effects against multiple RONS generated in diseases remain elusive. Here we propose to develop bioinspired melanin nanoparticles (MeNPs) for more potent and safer antioxidative therapy. While melanin is known to function as a potential radical scavenger, its antioxidative mechanisms are far from clear and its applications for the treatment of RONS-associated diseases have yet to be well explored. In this study, we provide for the first time exhaustive characterization of the activities of MeNPs against multiple RONS including O2•−, H2O2, •OH, •NO, and ONOO−, the main toxic RONS generated in diseases. The potential of MeNPs for antioxidative therapy has also been evaluated in vitro and in a rat model of ischemic stroke. In addition to the broad defense against these RONS, MeNPs can also attenuate the RONS-triggered inflammatory responses through suppressing the expression of inflammatory mediators and cytokines. In vivo results further demonstrate that these unique multi-antioxidative, anti-inflammatory and biocompatible features of MeNPs contribute to their effective protection of ischemic brains with negligible side effects.

The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveals that the lipophilic tails of lipid-PEG dictate its dissociation rate from NP surface, determining the uptake by tumor cells and macrophages, pharmacokinetics, biodistribution, and gene silencing efficacy of these hybrid siRNA NPs. Based on our observations, we here propose that lipid-PEGs with long and saturated lipophilic tails might be required for effective siRNA delivery to tumor cells and gene silencing of the lipid-polymer hybrid NPs after systemic administration.

A visible light active photocatalytic system based on two-dimensional (2D) TaS2 nanosheets with an integrated electron mediator (M) was developed for solar fuel production from CO2 in a biocatalyzed artificial photosynthesis system. The integration of M to TaS2 was realized through sequential functionalization by pegylation with lipoic acid conjugated PEG (LA–PEG), surface assembly of graphene (GR), and final integration of M. The photocatalytic activities of the resultant photocatalysts with different degrees of functionalization were evaluated by the photo-regeneration efficiency of NADH from NAD+ under visible light irradiation. Compared with non-functionalized TaS2 nanosheets that could only regenerate 39.7 ± 1.9% of NAD+ to NADH in the presence of dispersed M, the wholly integrated photocatalyst termed as TaS2–PEG–GR–M exhibited significantly improved efficiency with a NADH regeneration yield up to 83.9 ± 2.2%, which was higher than most of the reported values. This NADH photo-regeneration process was then coupled with formate dehydrogenase (FateDH) catalyzed synthesis of formic acid from CO2. By using TaS2–PEG–GR–M as a catalyst for NADH photo-regeneration, the formic acid concentration reached 101.4 ± 3.5 mM, which was about 2.5-fold higher than that obtained with the non-functionalized TaS2 nanosheets. Based on detailed investigations of the photochemical and electrochemical properties, the photo-induced electron transfer mechanism involved in the TaS2 nanosheets-based artificial photosynthesis system is discussed. The significantly enhanced reaction efficiency of the artificial photosynthesis system using the integrated TaS2–PEG–GR–M as the photocatalyst was considered to be mainly benefited from the increased hydrophilicity, elimination of electron back-flow and recombination of photogenerated electrons and holes, as well as the shortened distance of electron transfer. The integrated TaS2–PEG–GR–M photocatalytic system also avoided contamination of M to the reaction system, and allowed reuse of the expensive M. The whole photocatalytic system retained 83% of its original activity after 10 cycles of reuse. The present research highlights the development of a new class of 2D transition metal dichalcogenide-based integrated photocatalysts for the efficient and direct formation of solar fuels and chemicals from CO2.

In this manuscript, we demonstrate that the in situ growth of fluorescent silicon (Si) nanomaterials is stimulated when organosilicane molecules interact with different green teas, producing multifunctional Si nanomaterials with controllable zero- (e.g., nanoparticles), two- (e.g., nanosheets), and three- (e.g., nanospheres) dimensional nanostructures. Such green tea-originated Si nanomaterials (GTSN) exhibit strong fluorescence (quantum yield: ∼19-30%) coupled with ultrahigh photostability, as well as intrinsic anti-cancer activity with high specificity (e.g., the GTSN can accurately kill various cancer cells, rather than normal cells). Taking advantage of these unique merits, we further performed systematic in vitro and in vivo experiments to interrogate the mechanism of the green tea- and GTSN-related cancer prevention. Typically, we found that the GTSN entered the cell nuclei and induced cell apoptosis/death of cancer cells. The prepared GTSN were observed in vivo to accumulate in the tumour tissues after 14-d post-injection, leading to an efficient inhibition of tumour growth. Our results open new avenues for designing novel multifunctional and side-effect-free Si nanomaterials with controllable structures.

Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high‐quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe2O3, and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe3+ can damage the tumor microenvironment (TME) through glutathione consumption and O2 production; ii) Generated O2 can be further catalyzed by MgO with oxygen vacancy to generate ·O2 −; iii) The Fe2+‐catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H2O2 in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe2+ and Fe3+ for continuous consumption of glutathione and H2O2 and constant production of ·OH and O2; v) The NSs can be triggered by a 650 nm laser to generate ·O2 − from O2 as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging‐guided breast cancer treatment.

Two-dimensional (2D) nanomaterials have drawn tremendous attention due to their unique physicochemical properties and promising applications in the fields of electronics, energy storage, and catalysis. Recently, the biomedicine community has gradually started to recognize the great potential of these nanostructured materials for biomedical applications - in particular those related to cancer therapy. In this review, we provide a brief overview of a few representative 2D nanomaterials, discuss their preparation strategies and physicochemical properties, and highlight their applications in cancer nanomedicine. We expect that this review will shed some light on the new opportunities associated with 2D nanomaterials for biomedical research.

Highlights A novel all-in-one fluorescent nanomedicine platform based on silicon nanoparticles (SiNPs) was developed for imaging-guided co-delivery of short interfering RNA (siRNA) and doxorubicin (DOX).The intracellular time-dependent release behaviors of siRNA and DOX were visually monitored by tracking the strong and stable fluorescence of SiNPs.The SiNPs-based nanocarriers displayed pronounced therapeutic efficiency on drug-resistant breast cancer cells. Electronic supplementary material The online version of this article (10.1007/s40820-019-0257-1) contains supplementary material, which is available to authorized users., The development of effective and safe vehicles to deliver small interfering RNA (siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics, which has emerged as a powerful platform to treat drug-resistant cancer cells. Herein, we describe the development of novel all-in-one fluorescent silicon nanoparticles (SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin (DOX). This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells (i.e., MCF-7/ADR cells). Typically, the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment (i.e., medium or RNase A) and imparted the responsive release behavior of siRNA, resulting in approximately 80% down-regulation of P-glycoprotein expression. Co-delivery of P-glycoprotein siRNA and DOX led to > 35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX, indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells. The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs. These data provide valuable information for designing effective RNA interference-based co-delivery carriers. Electronic supplementary material The online version of this article (10.1007/s40820-019-0257-1) contains supplementary material, which is available to authorized users.

A Z-scheme heterojunction with high separation efficiency of photogenerated electrons and holes and enhanced reduction/oxidation potentials, which can enhance reactive oxygen species generation and photothermal conversion efficiency, exhibits tremendous potential in photonic theranostics. Herein, antimonene nanosheets (Sb NSs) are functionalized with photosensitizer 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,12H-porphine (THPP) and a poly(ethylene glycol) (PEG) modifier. The Sb-THPP-PEG NSs thus fabricated are found to form a Z-scheme heterojunction structure between Sb and THPP, based on their valence band and bandgap level analysis. The Z-scheme heterojunction structure enables the Sb-THPP-PEG NSs multiple promising features for cancer therapy. Firstly, due to improved electron-hole pairs separation efficiency and redox potential, new reactive oxygen species •O2 - is generated, besides the production of 1 O2 by THPP. Secondly, the assembly of THPP enhances the NIR-light-to-heat conversion of Sb NS, a photothermal conversion efficiency as high as 44.6% is obtained by this Sb-THPP-PEG NSs photonic nanomedicine. Moreover, the photothermal, fluorescent, and photoacoustic imaging properties of Sb-THPP-PEG NSs allow multimodal imaging-guided tumor treatment.

Photonic therapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)), features easy handling, good targeting, high curative effect and lower side effects compared to other treatments, thus showing considerable potential in cancer treatment. However, adverse tumor microenvironment, low light conversion efficiency, and inherent toxicity of photonic agents limit their further application in clinic. In this work, hollow mesoporous MnO2 nanoparticles (NPs) loaded with photosensitizer chlorin e6 and coated with folic acid-functionalized polydopamine were fabricated, and used as a platform for photonic therapy. The NPs enabled accurately controlled drug release, and sustainable and extensive O2 production by reacting with endogenous H2O2 in vitro. In addition, the NPs allowed efficient NIR light-to-heat conversion, owing to the core-shell MnO2/polydopamine structure. With the synergy of folic acid mediated active targeting and enhanced permeability and retention effect mediated passive targeting, a pronounced NPs accumulation at the tumor sites of mouse model was observed. The NPs also exhibited excellent biodegradation properties, alleviating the possible concerns about the long-term safety of photonic agents. Finally, a combination of O2-strengthened PDT and PTT resulted in effective tumor growth inhibition upon irradiation with 660 nm and 808 nm laser in vivo treatment. The above features of the devised NPs highlight their potential for improved cancer therapy and imaging.

Excessive reactive oxygen species (ROS), as effective cancer therapeutic agents, can promote tumor apoptosis. However, the clinical applications of ROS-mediated cancer therapies still have many limitations, such as self-defects of traditional photosensitizer, adverse tumor microenvironment (TME), and insufficient ROS production. Here, two-dimensional and highly oxidized ilmenite nanosheets (HOIL NSs, formula: FeTiO3@Fe2O3), one of perovskite analogues, were developed through combining ball-milling, probe sonication assisted liquid exfoliation, and probe sonication assisted surface oxidation. The HOIL NSs with surface oxidized Fe2O3 shell and FeTiO3 core cleverly developed a direct Z-scheme heterojunction, in which much stronger oxidation and reduction potentials in the valence band (VB) of Fe2O3 and the conduction band (CB) of FeTiO3 respectively were obtained via recombining the electrons in the CB of Fe2O3 with the holes in the VB of FeTiO3. Under irradiation of 650 nm laser, the generation of O2− from O2 and OH from OH− on the CB of FeTiO3 and VB of Fe2O3, respectively, were enhanced largely. Besides, the Fe2O3 shell and Fe3+/Fe2+ inside HOIL NSs can not only damage the TME through glutathione consumption and O2 production, but also produce OH by Fenton reaction. Moreover, the NSs can be triggered by an 808 nm laser to generate local hyperthermia for photothermal therapy. The fluorescent and photothermal imaging capabilities of the HOIL-PEG NSs also allow dual-modal imaging-guided cancer therapy.

Biochemical analysis in reliable, low-toxicity, and real-time manners are essentially important for exploring and unraveling biological events and related mechanisms. Silicon nanomaterial-based sensors and probes have potentiality to satisfy the above-mentioned requirements. Herein, we present an overview of the recent significant improvement in large-scale and facile synthesis of high-quality silicon nanomaterials and the research progress of biosensing and bioimaging analysis based on silicon nanomaterials. We especially illustrate the advanced applications of silicon nanomaterials in the field of ultrasensitive biomolecular detection and dynamic biological imaging analysis, with a focus on real-time and long-term detection. In the final section of this review, we discuss the major challenges and promising development in this domain.

Cancer hallmarks allow the complexity and heterogeneity of tumor biology to be better understood, leading to the discovery of various promising targets for cancer therapy. An amorphous iron oxide nanoparticle (NP)-based RNAi strategy is developed to co-target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton-like reaction. This strategy has the following features for systemic siRNA delivery: 1) siRNA encapsulation within NPs for improving systemic stability; 2) effective endosomal escape through osmotic pressure and/or endosomal membrane oxidation; 3) small size for enhancing tumor tissue penetration; and 4) triple functions (RNAi, Fenton-like reaction, and MRI) for combinatorial therapy and in vivo tracking.

While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, the effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core. When the rationally designed, long circulating polymeric NPs accumulate in tumor tissues after intravenous administration, the targeted siRNA-TCPA complexes can be rapidly released via TME pH-mediated NP disassembly for subsequent specific targeting of tumor cells and cytosolic transport, thus achieving efficient gene silencing. In vivo results further demonstrate that the multistaged NP delivery of siRNA against bromodomain 4 (BRD4), a recently discovered target protein that regulates the development and progression of prostate cancer (PCa), can significantly inhibit PCa tumor growth.

Fluorescent imaging techniques for visualization of nuclear structure and function in live cells are fundamentally important for exploring major cellular events. The ideal cellular labeling method is capable of realizing label-free, in situ, real-time, and long-term nucleus labeling in live cells, which can fully obtain the nucleus-relative information and effectively alleviate negative effects of alien probes on cellular metabolism. However, current established fluorescent probes-based strategies (e.g., fluorescent proteins-, organic dyes-, fluorescent organic/inorganic nanoparticles-based imaging techniques) are unable to simultaneously realize label-free, in situ, long-term, and real-time nucleus labeling, resulting in inevitable difficulties in fully visualizing nuclear structure and function in live cells. To this end, we present a type of bioinspired fluorescent probes, which are highly efficacious for in situ and label-free tracking of nucleus in long-term and real-time manners. Typically, the bioinspired polydopamine (PDA) nanoparticles, served as fluorescent probes, can be readily synthesized in situ within live cell nucleus without any further modifications under physiological conditions (37 °C, pH ∼7.4). Compared with other conventional nuclear dyes (e.g., propidium iodide (PI), Hoechst), superior spectroscopic properties (e.g., quantum yield of ∼35.8% and high photostability) and low cytotoxicity of PDA-based probes enable long-term (e.g., 3 h) fluorescence tracking of nucleus. We also demonstrate the generality of this type of bioinspired fluorescent probes in different cell lines and complex biological samples.

Photothermal therapy (PTT) has shown significant potential for cancer therapy. However, developing nanomaterials (NMs)-based photothermal agents (PTAs) with satisfactory photothermal conversion efficacy (PTCE) and biocompatibility remains a key challenge. Herein, a new generation of PTAs based on two-dimensional (2D) antimonene quantum dots (AMQDs) was developed by a novel liquid exfoliation method. Surface modification of AMQDs with polyethylene glycol (PEG) significantly enhanced both biocompatibility and stability in physiological medium. The PEG-coated AMQDs showed a PTCE of 45.5%, which is higher than many other NMs-based PTAs such as graphene, Au, MoS2, and black phosphorus (BP). The AMQDs-based PTAs also exhibited a unique feature of NIR-induced rapid degradability. Through both in vitro and in vivo studies, the PEG-coated AMQDs demonstrated notable NIR-induced tumor ablation ability. This work is expected to expand the utility of 2D antimonene (AM) to biomedical applications through the development of an entirely novel PTA platform.

Biocatalyzed artificial photosynthesis systems provide a promising strategy to store solar energy in a great variety of chemicals. However, the lack of direct interface between the light-capturing components and the oxidoreductase generally hinders the trafficking of the chemicals and photo-excited electrons into the active center of the redox biocatalysts. To address this problem, a completely integrated artificial photosynthesis system for enhanced electronic energy-transfer efficacy is reported by combining co-axial electrospinning/electrospray and layer-by-layer (LbL) self-assembly. The biocatalysis part including multiple oxidoreductases and coenzymes NAD(H) was in situ encapsulated inside the lumen polyelectrolyte-doped hollow nanofibers or microcapsules fabricated via co-axial electrospinning/electrospray; while the precise and spatial arrangement of the photocatalysis part, including electron mediator and photosensitizer for photo-regeneration of the coenzyme, was achieved by ion-exchange interaction-driven LbL self-assembly. The feasibility and advantages of this integrated artificial photosynthesis system is fully demonstrated by the catalyzed cascade reduction of CO2 to methanol by three dehydrogenases (formate, formaldehyde, and alcohol dehydrogenases), incorporating the photo-regeneration of NADH under visible-light irradiation. Compared to solution-based systems, the methanol yield increases from 35.6% to 90.6% using the integrated artificial photosynthesis. This work provides a novel platform for the efficient and sustained production of a broad range of chemicals and fuels from sunlight.

Fluorescent silicon nanoparticles (SiNPs) attract considerable attention owing to their intrinsic advantages, including relatively strong fluorescence coupled with robust photostability, rich resource support and relatively low cost, industrial maturity, and good biocompatibility. Extensive efforts are devoted to developing effective methods for the synthesis of hydrogen or halogen-terminated SiNPs, which nevertheless need further surface modification to improve their stability and solubility for wide-ranging applications. Notably, recent years have witnessed the development of various aqueous synthetic strategies for direct preparation of highly fluorescent and photostable SiNPs in the aqueous phase, facilitating the promotion of this promising material for myriad optical applications. Here, a concise discussion of the latest exciting research progress of the preparation of SiNPs is given, with a focus on water-dispersible SiNPs synthesized in the aqueous phase. In addition, representative optical applications of SiNPs in bioimaging and sensing are also summarized. Finally, the opportunities and challenges of fluorescent-SiNP-based optical applications are discussed.

As a novel 2D material, black phosphorus (BP) nanosheets are considered as a promising candidate for drug delivery platform for synergistic chemo/photothermal therapy. However, the intrinsic instability of bare BP poses a challenge in its biomedical applications. To date, some strategies have been employed to prevent BP from rapid ambient degradation. Unfortunately, most of these strategies are not suitable for the drug delivery systems. Here, a simple polydopamine modification method is developed to enhance the stability and photothermal performance of bare BP nanosheets. Then, this nanocapsule is used as a multifunctional codelivery system for the targeted chemo, gene, and photothermal therapy against multidrug‐resistant cancer. The enhanced tumor therapy effect is demonstrated by both in vitro and in vivo studies.

Antimonene (AM) is a recently described two-dimensional (2D) elemental layered material. In this study, a novel photonic drug-delivery platform based on 2D PEGylated AM nanosheets (NSs) is developed. The platform's multiple advantages include: i) excellent photothermal properties, ii) high drug-loading capacity, iii) spatiotemporally controlled drug release triggered by near-infrared (NIR) light and moderate acidic pH, iv) superior accumulation at tumor sites, v) deep tumor penetration by both extrinsic stimuli (i.e., NIR light) and intrinsic stimuli (i.e., pH), vi) excellent multimodal-imaging properties, and vii) significant inhibition of tumor growth with no observable side effects and potential degradability, thus addressing several key limitations of cancer nanomedicines. The intracellular fate of the prepared NSs is also revealed for the first time, providing deep insights that improve cellular-level understanding of the nano-bio interactions of AM-based NSs and other emerging 2D nanomaterials. To the best of knowledge, this is the first report on 2D AM-based photonic drug-delivery platforms, possibly marking an exciting jumping-off point for research into the application of 2D AM nanomaterials in cancer theranostics.

Single atom non-metal two-dimensional (2D) nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) were prepared through a novel top-down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform was developed, which exhibited multiple promising features for cancer therapy and imaging, including (i) efficient NIR light to heat conversion with a high photothermal conversion efficiency of 42.5%, (ii) high drug-loading capacity and triggered drug release by NIR light and moderate acidic pH, (iii) strong accumulation at tumor sites, (iv) multimodal imaging properties (photoacoustic, photothermal and fluorescent imaging), and (v) complete tumor ablation and excellent biocompatibility. To the best of our knowledge, this is the first report on the top-down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multi-modal imaging-guided drug delivery platform. We also expect the newly prepared B NSs to provide a robust and useful 2D nanoplatform for various biomedical applications.

A biocatalyzed artificial photosynthesis system (APS) based on porphyrin/SiO2/Cp*Rh(bpy)Cl hybrid nanoparticles (TCPP/SiO2/Rh HNPs) to mimic chloroplasts in green plant is reported. The TCPP/SiO2/Rh HNPs are fabricated via sol-gel reaction of silica precursors functionalized with photosensitizer (porphyrin, TCPP) and electron mediator (Cp*Rh(bpy)Cl, M); while the integration of enzyme and coenzyme nicotinamide adenine dinucleotide (NAD)(H), on the outer surface of the HNPs is achieved through electro-static-interaction-driven assembling under the entanglement of a negatively charged polyelectrolyte. The chloroplast-mimicking, highly integrated APS exhibits remarkably superior performance over a free system such that the regeneration of NADH is improved from 11% to 75%, and the synthesis of formic acid from CO2 increased from 15 to 100 mu mol. Based on the detailed investigations into the photochemical and electrochemical properties, it is speculated that the covalent linking of the photosensitizer and electron mediator via silicon hydride bonds, and the formed SiO2 network through sol-gel reaction, may form intramolecular and intermolecular electron transfer chains to direct more efficient electron transfer from TCPP to M. Such intramolecular and intermolecular electrons and energy transfer, cooperated with the integrated biocatalytic process, lead to the significantly enhanced overall reaction efficiency. Moreover, the integrated APS also allows facile recycling of expensive M, enzymes, and cofactors.

Near-infrared (NIR)-absorbing metal-based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal-controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta-derived nanomaterials represent promising candidates for biomedical applications. However, Ta-based nanomaterials by themselves have not been explored for NIR-mediated photothermal ablation therapy. In this work, an innovative Ta-based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS2) nanosheets (NSs) is reported for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS2 NSs exhibit multiple unique features including (i) efficient NIR light-to-heat conversion with a high photothermal conversion efficiency of 39%, (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat-enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. It is expected that this multifunctional NS platform can serve as a promising candidate for imaging-guided cancer therapy and selection of cancer patients with high tumor accumulation.

The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP-mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)-responsive polyprodrug is reported that can self-assemble into stable NPs with high drug loading. This new NP platform is composed of the following key components: (i) polyprodrug inner core that can respond to ROS for triggered release of intact therapeutic molecules, (ii) polyethylene glycol (PEG) outer shell to prolong blood circulation; and (iii) surface-encoded internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration. These targeted ROS-responsive polyprodrug NPs show significant inhibition of tumor cell growth both in vitro and in vivo.

2D black phosphorus (BP) nanomaterials are presented as a delivery platform. The endocytosis pathways and biological activities of PEGylated BP nanosheets in cancer cells are revealed for the first time. Finally, a triple-response combined therapy strategy is achieved by PEGylated BP nanosheets, showing a promising and enhanced antitumor effect.