Low‐Saturation‐Intensity,High‐Photostability,and High‐Resolution STED Nanoscopy Assisted by CsPbBr3 Quantum Dots

Stimulated emission depletion (STED) nanoscopy is one of the most promising super‐resolution imaging techniques for microstructure imaging. Commercial CdSe@ZnS quantum dots are used as STED probes and ≈50 nm lateral resolution is obtained. Compared with other quantum dots, perovskite CsPbBr₃ nanoparticles (NPs) possess higher photoluminescence quantum yield and larger absorption cross‐section, making them a more effective probe for STED nanoscopy. In this study, CsPbBr₃ NPs are used as probes for STED nanoscopy imaging. The fluorescence intensity of the CsPbBr₃ sample is hardly weakened at all after 200 min irradiation with a 39.8 mW depletion laser, indicating excellent photobleaching resistance of the CsPbBr₃ NPs. The saturation intensity of the CsPbBr₃ NPs is extremely low and estimated to be only 0.4 mW (0.126 MW cm^?2). Finally, an ultrahigh lateral resolution of 20.6 nm is obtained for a single nanoparticle under 27.5 mW STED laser irradiation in CsPbBr₃‐based STED nanoscopy imaging, which is a tenfold improvement compared with confocal microscopy. Because of its high fluorescence stability and ultrahigh resolution under lower depletion power, CsPbBr₃‐assisted STED nanoscopy has great potential to investigate microstructures that require super‐resolution and long‐term imaging.     

Bright Far‐Red/Near‐Infrared Conjugated Polymer Nanoparticles for In Vivo Bioimaging

A highly emissive far‐red/near‐infrared (FR/NIR) fluorescent conjugated polymer (CP), poly[(9,9‐dihexylfluorene)‐co‐2,1,3‐benzothiadiazole‐co‐4,7‐di(thiophen‐2‐yl)‐2,1,3‐benzothiadiazole] (PFBTDBT10) is designed and synthesized via Suzuki polymerization. Formulation of PFBTDBT10 using 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] (DSPE‐PEG₂₀₀₀) and DSPE‐PEG₅₀₀₀‐folate as the encapsulation matrix yielded CP‐loaded DSPE‐PEG‐folic acid nanoparticles (CPDP‐FA NPs) with bright FR/NIR fluorescence (27% quantum yield) and a large Stoke's shift of 233 nm in aqueous solution. CPDP‐FA NPs show improved thermal/photostabilities and larger Stoke's shifts as compared to commercially available quantum dots (Qdot 655) and organic dyes such as Alexa Fluor 555 and Rhodamine 6G. In vivo studies of CPDP‐FA NPs on a hepatoma H22 tumor‐bearing mouse model reveal that they could serve as an efficient FR/NIR fluorescent probe for targeted in vivo fluorescence imaging and cancer detection in a high contrast and specific manner. Together with the negligible in vivo toxicity, CPDP‐FA NPs are promising FR/NIR fluorescent probes for future in vivo applications.     

Eccentric Loading of Fluorogen with Aggregation‐Induced Emission in PLGA Matrix Increases Nanoparticle Fluorescence Quantum Yield for Targeted Cellular Imaging

A simple strategy is developed to prepare eccentrically or homogeneously loaded nanoparticles (NPs) using poly (DL‐lactide‐co‐glycolide) (PLGA) as the encapsulation matrix in the presence of different amounts of polyvinyl alcohol (PVA) as the emulsifier. Using 2,3‐bis(4‐(phenyl(4‐(1,2,2‐triphenylvinyl)‐phenyl)amino)‐phenyl)‐fumaronitrile (TPETPAFN), a fluorogen with aggregation‐induced emission (AIE) characteristics, as an example, the eccentrically loaded PLGA NPs show increased fluorescence quantum yields (QYs) as compared to the homogeneously loaded ones. Field emission transmission electron microscopy and fluorescence lifetime measurements reveal that the higher QY of the eccentrically loaded NPs is due to the more compact aggregation of AIE fluorogens that restricts intramolecular rotations of phenyl rings, which is able to more effectively block the non‐radiative decay pathways. The eccentrically loaded NPs show far red/near infrared emission with a high fluorescence QY of 34% in aqueous media. In addition, by using poly([lactide‐co‐glycolide]‐b‐folate [ethylene glycol]) (PLGA‐PEG‐folate) as the co‐encapsulation matrix, the obtained NPs are born with surface folic acid groups, which are successfully applied for targeted cellular imaging with good photostability and low cytotoxicity. Moreover, the developed strategy is also demonstrated for inorganic‐component eccentrically or homogeneously loaded PLGA NPs, which facilitates the synthesis of polymer NPs with controlled internal architectures.     

Self‐Assembled Large Au Nanoparticle Arrays with Regular Hot Spots for SERS

The cost‐effective self‐assembly of 80 nm Au nanoparticles (NPs) into large‐domain, hexagonally close‐packed arrays for high‐sensitivity and high‐fidelity surface‐enhanced Raman spectroscopy (SERS) is demonstrated. These arrays exhibit specific optical resonances due to strong interparticle coupling, which are well reproduced by finite‐difference time‐domain (FDTD) simulations. The gaps between NPs form a regular lattice of hot spots that enable a large amplification of both photoluminescence and Raman signals. At smaller wavelengths the hot spots are extended away from the minimum‐gap positions, which allows SERS of larger analytes that do not fit into small gaps. Using CdSe quantum dots (QDs) a 3–5 times larger photoluminescence enhancement than previously reported is experimentally demonstrated and an unambiguous estimate of the electromagnetic SERS enhancement factor of ≈10⁴ is obtained by direct scanning electron microscopy imaging of QDs responsible for the Raman signal. Much stronger enhancement of ≈10⁸ is obtained at larger wavelengths for benzenethiol molecules penetrating the NP gaps.     

Fabry–Pérot Oscillation and Room Temperature Lasing in Perovskite Cube‐Corner Pyramid Cavities

Recently, organometal halide perovskite‐based optoelectronics, particularly lasers, have attracted intensive attentions because of its outstanding spectral coherence, low threshold, and wideband tunability. In this work, high‐quality CH₃NH₃PbBr₃ single crystals with a unique shape of cube‐corner pyramids are synthesized on mica substrates using chemical vapor deposition method. These micropyramids naturally form cube‐corner cavities, which are eminent candidates for small‐sized resonators and retroreflectors. The as‐grown perovskites show strong emission ≈530 nm in the vertical direction at room temperature. A special Fabry–Pérot (F–P) mode is employed to interpret the light confinement in the cavity. Lasing from the perovskite pyramids is observed from 80 to 200 K, with threshold ranging from ≈92 µJ cm^?2 to 2.2 mJ cm^?2, yielding a characteristic temperature of T₀ = 35 K. By coating a thin layer of Ag film, the threshold is reduced from ≈92 to 26 µJ cm^?2, which is accompanied by room temperature lasing with a threshold of ≈75 µJ cm^?2. This work advocates the prospect of shape‐engineered perovskite crystals toward developing micro‐sized optoelectronic devices and potentially investigating light–matter coupling in quantum optics.     

Chiral Octahydro‐Binaphthol Compound‐Based Thermally Activated Delayed Fluorescence Materials for Circularly Polarized Electroluminescence with Superior EQE of 32.6% and Extremely Low Efficiency Roll‐Off

Circularly polarized organic light‐emitting diodes (CP‐OLEDs) are particularly favorable for the direct generation of CP light, and they demonstrate a promising application in 3D display. However, up to now, such CP devices have suffered from low brightness, insufficient efficiency, and serious efficiency roll‐off. In this study, a pair of octahydro‐binaphthol ( OBN )‐based chiral emitting enantiomers, (R/S)‐OBN‐Cz , are developed by ingeniously merging a chiral source and a luminophore skeleton. These chirality–acceptor–donor (C–A–D)‐type and rod‐like compounds concurrently generate thermally activated delayed fluorescence with a small ΔE_ST of 0.037 eV, as well as a high photoluminescence quantum yield of 92% and intense circularly polarized photoluminescence with dissymmetry factors (|g_PL|) of ≈2.0 × 10^?3 in thin films. The CP‐OLEDs based on (R/S)‐OBN‐Cz enantiomers not only display obvious circularly polarized electroluminescence signals with a |g_EL| of ≈2.0 × 10^?3, but also exhibit superior efficiencies with maximum external quantum efficiency (EQE_max) up to 32.6% and extremely low efficiency roll‐off with an EQE of 30.6% at 5000 cd m^?2, which are the best performances among the reported CP devices to date.     

AIE Nanoparticles with High Stimulated Emission Depletion Efficiency and Photobleaching Resistance for Long‐Term Super‐Resolution Bioimaging

Stimulated emission depletion (STED) nanoscopy is a typical super‐resolution imaging technique that has become a powerful tool for visualizing intracellular structures on the nanometer scale. Aggregation‐induced emission (AIE) luminogens are ideal fluorescent agents for bioimaging. Herein, long‐term super‐resolution fluorescence imaging of cancer cells, based on STED nanoscopy assisted by AIE nanoparticles (NPs) is realized. 2,3‐Bis(4‐(phenyl(4‐(1,2,2‐triphenylvinyl)phenyl)amino)phenyl) fumaronitrile (TTF), a typical AIE luminogen, is doped into colloidal mesoporous silica to form fluorescent NPs. TTF@SiO₂ NPs bear three significant features, which are all essential for STED nanoscopy. First, their STED efficiency can reach more than 60%. Second, they are highly resistant to photobleaching, even under long‐term and high‐power STED light irradiation. Third, they have a large Stokes' shift of ≈150 nm, which is beneficial for restraining the fluorescence background induced by the STED light irradiation. STED nanoscopy imaging of TTF@SiO₂‐NPs‐stained HeLa cells is performed, exhibiting a high lateral spatial resolution of 30 nm. More importantly, long‐term (more than half an hour) super‐resolution cell imaging is achieved with low fluorescence loss. Considering that AIE luminogens are widely used for organelle targeting, cellular mapping, and tracing, AIE‐NPs‐based STED nanoscopy holds great potential for many basic biomedical studies that require super‐resolution and long‐term imaging.     

Molecular Engineering of an Organic NIR‐II Fluorophore with Aggregation‐Induced Emission Characteristics for In Vivo Imaging

Design and synthesis of new fluorophores with emission in the second near‐infrared window (NIR‐II, 1000–1700 nm) have fueled the advancement of in vivo fluorescence imaging. Organic NIR‐II probes particularly attract tremendous attention due to excellent stability and biocompatibility, which facilitate clinical translation. However, reported organic NIR‐II fluorescent agents often suffer from low quantum yield and complicated design. In this study, the acceptor unit of a known NIR‐I aggregation‐induced emission (AIE) luminogen (AIEgen) is molecularly engineered by varying a single atom from sulfur to selenium, leading to redshifted absorption and emission spectra. After formulation of the newly prepared AIEgen, the resultant AIE nanoparticles (referred as L897 NPs) have an emission tail extending to 1200 nm with a high quantum yield of 5.8%. Based on the L897 NPs, noninvasive vessel imaging and lymphatic imaging are achieved with high signal‐to‐background ratio and deep penetration. Furthermore, the L897 NPs can be used as good contrast agents for tumor imaging and image‐guided surgery due to the high tumor/normal tissue ratio, which peaks at 9.0 ± 0.6. This work suggests a simple strategy for designing and manufacturing NIR‐II AIEgens and demonstrates the potential of NIR‐II AIEgens in vessel, lymphatic, and tumor imaging.     

Solid‐State Carbon Dots with Red Fluorescence and Efficient Construction of Dual‐Fluorescence Morphologies

Stable solid‐state red fluorescence from organosilane‐functionalized carbon dots (CDs) with sizes around 3 nm is reported for the first time. Meanwhile, a novel method is also first reported for the efficient construction of dual‐fluorescence morphologies. The quantum yield of these solid‐state CDs and their aqueous solution is 9.60 and 50.7%, respectively. The fluorescence lifetime is 4.82 ns for solid‐state CDs, and 15.57 ns for their aqueous solution. These CDs are detailedly studied how they can exhibit obvious photoluminescence overcoming the self‐quenching in solid state. Luminescent materials are constructed with dual fluorescence based on as‐prepared single emissive CDs (red emission) and nonfluorescence media (starch, Al₂O₃, and RnOCH₃COONa), with the characteristic peaks located at nearly 440 and 600 nm. Tunable photoluminescence can be successfully achieved by tuning the mass ratio of CDs to solid matrix (such as starch). These constructed dual‐fluorescence CDs/starch composites can also be applied in white light‐emitting diodes with UV chips (395 nm), and oxygen sensing.     

Lipid‐PEG‐Folate Encapsulated Nanoparticles with Aggregation Induced Emission Characteristics: Cellular Uptake Mechanism and Two‐Photon Fluorescence Imaging

Folate functionalized nanoparticles (NPs) that contain fluorogens with aggregation‐induced emission (AIE) characteristics are fabricated to show bright far‐red/near‐infrared fluorescence, a large two‐photon absorption cross section and low cytotoxicity, which are internalized into MCF‐7 cancer cells mainly through caveolae‐mediated endocytosis. One‐photon excited in vivo fluorescence imaging illustrates that these AIE NPs can accumulate in a tumor and two‐photon excited ex vivo tumor tissue imaging reveals that they can be easily detected in the tumor mass at a depth of 400 μm. These studies indicate that AIE NPs are promising alternatives to conventional TPA probes for biological imaging.     

All‐Solution‐Processed Pure Formamidinium‐Based Perovskite Light‐Emitting Diodes

All‐solution‐processed pure formamidinium‐based perovskite light‐emitting diodes (PeLEDs) with record performance are successfully realized. It is found that the FAPbBr₃ device is hole dominant. To achieve charge carrier balance, on the anode side, PEDOT:PSS 8000 is employed as the hole injection layer, replacing PEDOT:PSS 4083 to suppress the hole current. On the cathode side, the solution‐processed ZnO nanoparticle (NP) is used as the electron injection layer in regular PeLEDs to improve the electron current. With the smallest ZnO NPs (2.9 nm) as electron injection layer (EIL), the solution‐processed PeLED exhibits a highest forward viewing power efficiency of 22.3 lm W^?1, a peak current efficiency of 21.3 cd A^?1, and an external quantum efficiency of 4.66%. The maximum brightness reaches a record 1.09 × 10⁵ cd m^?2. A record lifetime T₅₀ of 436 s is achieved at the initial brightness of 10 000 cd m^?2. Not only do PEDOT:PSS 8000 HIL and ZnO NPs EIL modulate the injected charge carriers to reach charge balance, but also they prevent the exciton quenching at the interface between the charge injection layer and the light emission layer. The subbandgap turn‐on voltage is attributed to Auger‐assisted energy up‐conversion process.     

Highly Luminescent 2D‐Type Slab Crystals Based on a Molecular Charge‐Transfer Complex as Promising Organic Light‐Emitting Transistor Materials

A new 2:1 donor (D):acceptor (A) mixed‐stacked charge‐transfer (CT) cocrystal comprising isometrically structured dicyanodistyrylbenzene‐based D and A molecules is designed and synthesized. Uniform 2D‐type morphology is manifested by the exquisite interplay of intermolecular interactions. In addition to its appealing structural features, unique optoelectronic properties are unveiled. Exceptionally high photoluminescence quantum yield (Φ _F ≈ 60%) is realized by non‐negligible oscillator strength of the S₁ transition, and rigidified 2D‐type structure. Moreover, this luminescent 2D‐type CT crystal exhibits balanced ambipolar transport (µ _h and µ _e of ≈10^?4 cm² V^?1 s^?1). As a consequence of such unique optoelectronic characteristics, the first CT electroluminescence is demonstrated in a single active‐layered organic light‐emitting transistor (OLET) device. The external quantum efficiency of this OLET is as high as 1.5% to suggest a promising potential of luminescent mixed‐stacked CT cocrystals in OLET applications.     

NIR‐II‐Excited Intravital Two‐Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR‐I AIE Luminogen

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal‐to‐background ratio (SBR) is highly desirable for the study and theranostics of vascular‐related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long‐wavelength absorption and aggregation‐induced near‐infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two‐photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR‐II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR‐II excitation. This study highlights the importance of developing NIR‐II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.     

Self‐Assembled Au/CdSe Nanocrystal Clusters for Plasmon‐Mediated Photocatalytic Hydrogen Evolution

Plasmon‐mediated photocatalytic systems generally suffer from poor efficiency due to weak absorption overlap and thus limited energy transfer between the plasmonic metal and the semiconductor. Herein, a near‐ideal plasmon‐mediated photocatalyst system is developed. Au/CdSe nanocrystal clusters (NCs) are successfully fabricated through a facile emulsion‐based self‐assembly approach, containing Au nanoparticles (NPs) of size 2.8, 4.6, 7.2, or 9.0 nm and CdSe quantum dots (QDs) of size ≈3.3 nm. Under visible‐light irradiation, the Au/CdSe NCs with 7.2 nm Au NPs afford very stable operation and a remarkable H₂‐evolution rate of (10× higher than bare CdSe NCs). Plasmon resonance energy transfer from the Au NPs to the CdSe QDs, which enhances charge‐carrier generation in the semiconductor and suppresses bulk recombination, is responsible for the outstanding photocatalytic performance. The approach used here to fabricate the Au/CdSe NCs is suitable for the construction of other plasmon‐mediated photocatalysts.     

Liquid‐Alloy‐Assisted Growth of 2D Ternary Ga2In4S9 toward High‐Performance UV Photodetection

2D ternary systems provide another degree of freedom of tuning physical properties through stoichiometry variation. However, the controllable growth of 2D ternary materials remains a huge challenge that hinders their practical applications. Here, for the first time, by using a gallium/indium liquid alloy as the precursor, the synthesis of high‐quality 2D ternary Ga₂In₄S₉ flakes of only a few atomic layers thick (≈2.4 nm for the thinnest samples) through chemical vapor deposition is realized. Their UV‐light‐sensing applications are explored systematically. Photodetectors based on the Ga₂In₄S₉ flakes display outstanding UV detection ability (R _λ = 111.9 A W^?1, external quantum efficiency = 3.85 × 10⁴%, and D* = 2.25 × 10¹¹ Jones@360 nm) with a fast response speed (τ_ring ≈ 40 ms and τ_decay ≈ 50 ms). In addition, Ga₂In₄S₉‐based phototransistors exhibit a responsivity of ≈10⁴ A W^?1@360 nm above the critical back‐gate bias of ≈0 V. The use of the liquid alloy for synthesizing ultrathin 2D Ga₂In₄S₉ nanostructures may offer great opportunities for designing novel 2D optoelectronic materials to achieve optimal device performance.     

Tri‐s‐triazine‐Based Crystalline Carbon Nitride Nanosheets for an Improved Hydrogen Evolution

Tri‐s‐triazine‐based crystalline carbon nitride nanosheets (CCNNSs) have been successfully extracted via a conventional and cost‐effective sonication–centrifugation process. These CCNNSs possess a highly defined and unambiguous structure with minimal thickness, large aspect ratios, homogeneous tri‐s‐triazine‐based units, and high crystallinity. These tri‐s‐triazine‐based CCNNSs show significantly enhanced photocatalytic hydrogen generation activity under visible light than g‐C₃N₄, poly (triazine imide)/Li⁺ Cl^–, and bulk tri‐s‐triazine‐based crystalline carbon nitrides. A highly apparent quantum efficiency of 8.57% at 420 nm for hydrogen production from aqueous methanol feedstock can be achieved from tri‐s‐triazine‐based CCNNSs, exceeding most of the reported carbon nitride nanosheets. Benefiting from the inherent structure of 2D crystals, the ultrathin tri‐s‐triazine‐based CCNNSs provide a broad range of application prospects in the fields of bioimaging, and energy storage and conversion.     

Rupturing C60 Molecules into Graphene‐Oxide‐like Quantum Dots: Structure,Photoluminescence, and Catalytic Application

The large‐scale synthesis of graphene‐oxide‐like quantum dots (GOLQDs) is reported by oxidizing C₆₀ molecules using a modified Hummers method with a yield of ≈25 wt% readily achieved. The GOLQDs are highly soluble in water and in addition to hexagons have other carbon rings in the structure. They have an average height of ≈1.2 nm and a diameter distribution of 0.6–2.2 nm after drying on substrates. First‐principle calculations indicate that a possible rupturing route may include the insertion of oxygen atoms to C C bonds in the C₆₀ molecule, followed by rupture of that C C bonds. The GOLQD suspension has a strong photoluminescence (PL) with peak position dependent on excitation wavelength. The PL is related to the size and emissive traps caused by oxygen‐containing groups. The GOLQDs also catalyze the oxidation of benzyl alcohol with a high selectivity.     

DNA‐Mediated Self‐Assembly of Plasmonic Antennas with a Single Quantum Dot in the Hot Spot

DNA self‐assembly is a powerful tool to arrange optically active components with high accuracy in a large parallel manner. A facile approach to assemble plasmonic antennas consisting of two metallic nanoparticles (40 nm) with a single colloidal quantum dot positioned at the hot spot is presented here. The design approach is based on DNA complementarity, stoichiometry, and steric hindrance principles. Since no intermediate molecules other than short DNA strands are required, the structures possess a very small gap (≈ 5 nm) which is desired to achieve high Purcell factors and plasmonic enhancement. As a proof‐of‐concept, the fluorescence emission from antennas assembled with both conventional and ultrasmooth spherical gold particles is measured. An increase in fluorescence is obtained, up to ≈30‐fold, compared to quantum dots without antenna.     

Monolayer Silane‐Coated,Water‐Soluble Quantum Dots

A one‐step method to produce ≈12 nm hydrodynamic diameter water‐soluble CdSe/ZnS quantum dots (QDs), as well as CdS/ZnS, ZnSe/ZnMnS/ZnS, AgInS₂/ZnS, and CuInS₂/ZnS QDs, by ligand exchange with a near‐monolayer of organosilane caps is reported. The method cross‐links the surface‐bound silane ligands such that the samples are stable on the order of months under ambient conditions. Furthermore, the samples may retain a high quantum yield (60%) over this time. Several methods to functionalize aqueous QD dispersions with proteins and fluorescent dyes have been developed with reaction yields as high as 97%.     

Layer‐by‐Layer Nanoparticles as an Efficient siRNA Delivery Vehicle for SPARC Silencing

Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC‐siRNA in the bilayers of layer‐by‐layer (LbL) nanoparticles (NPs) with poly(L‐arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO‐siRNA and SPARC‐siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC‐gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT‐PCR. The multilayer SPARC‐siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC‐gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real‐time cell proliferation and MTT cell assay, indicated that the SPARC‐siRNA‐loaded LbL NPs are non‐toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non‐viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics.