Biodegradable Plant Oil-Based Bioadhesive with Ultrastrong Wet-Tissue Adhesion for Instant Sealing Hemostasis.

The key to saving lives is to achieve instant and effective sealing hemostasis in the event of emergency bleeding. Herein, a plant oil-based EMTA/Zn2+ bioadhesive is prepared by a facile reaction of epoxidized soybean oil (ESO) with methacrylic acid (MAA) and tannic acid (TA), followed by the addition of zinc ions for coordination with TA. The EMTA/Zn2+ bioadhesive can be rapidly cured in situ at the wound site through photo-cross-linking under ultraviolet (UV) light-emitting diode (LED) irradiation within 30 s, achieving ultrastrong wet-tissue adhesion performance of 92.4 and 51.8 kPa to porcine skin and aortic skin after 7 days underwater, respectively. Especially, the EMTA/Zn2+ bioadhesive exhibits outstanding sealing performance in vitro with the high burst pressure of 525 mmHg (70 kPa) and 337.5 mmHg (45 kPa) to porcine skin and aortic skin, respectively. Moreover, the EMTA/Zn2+ bioadhesive not only has outstanding hemocompatibility and good biodegradability but also exhibits excellent cytocompatibility and antibacterial properties. Notably, the EMTA/Zn2+ bioadhesive has remarkable instant sealing hemostatic ability for hemorrhaging liver in vivo. Therefore, the prepared plant oil-based EMTA/Zn2+ bioadhesive can serve as a charming alternative candidate for instant sealing hemostasis in clinical applications, especially in traumatic internal organs and arterial bleeding.

Preparation of PMMA-Based Temperature/pH Responsive Nanoparticles Encapsulating 5-Fluorouracil and Methotrexate In Situ by One-Pot Dispersion Photopolymerization.

In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer-Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.

Rapid hemostatic antibacterial self-gelling powder based on methacryloylsulfonyl betaine and quaternized carboxymethyl chitosan.

Hemostatic powders can be used for deep wounds and wounds with irregular shapes that are frequently inaccessible to traditional hemostatic dressings like hemostatic gauze, sponges, and foams. In this study, sulfobetaine methacrylate (SBMA) and quaternized carboxymethyl chitosan (QCCS) were combined to create an antibacterial hemostatic hydrogel through photopolymerization under green LED irradiation, which was then changed into PSBMA/QCCS powder. PSBMA/QCCS powder could quickly form hydrogel with strong wet adhesion. The internal structure, water absorption capacity, and adhesion properties of the powder were evaluated. The coagulation ability, antimicrobial properties, and biocompatibility of the powder were also characterized. The PSBMA/QCCS powder could aggregate blood cells and platelets to enhance hemostasis. Meanwhile, PSBMA/QCCS powder also showed effective antibacterial ability against both gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli). In summary, PSBMA/QCCS powder is a promising hemostatic agent with the characteristics of quick hemostasis, tough wet adhesion, satisfactory biocompatibility, considerable antibacterial effect, and adaptability to any irregularly shaped wounds.

Nanogels co-loading paclitaxel and curcumin prepared in situ through photopolymerization at 532 nm for synergistically suppressing breast tumors.

Combined chemotherapy plays an increasingly important and practical role in the clinical treatment of malignant tumor. In this study, paclitaxel (PTX) and curcumin (Cur) are simultaneously encapsulated into nanogels (termed as NG-PC) in situ by microemulsion photopolymerization at 532 nm for synergistically suppressing breast tumors. NG-PC with a size of 180 nm and a low polydispersity index (PDI < 0.2) presents a controlled and cumulative release of PTX and Cur within 90 h. Moreover, NG-PC displays a remarkable killing effect against 4T1 and MCF-7 cells. In vivo antitumor evaluation on 4T1 tumor-bearing mice demonstrates that NG-PC has significantly higher ability to inhibit tumor growth, inducing necrosis, apoptosis and suppression of proliferation than that of a single drug. Our research provides a facile method to prepare a nano-drug delivery platform with excellent drug co-loading ability and synergistic antitumor effect.

Temperature/pH-responsive carmofur-loaded nanogels rapidly prepared via one-pot laser-induced emulsion polymerization.

Tumor microenvironment-responsive nanogels loading antitumor drugs can improve the chemotherapy efficiency due to their suitable size, great hydrophilicity, excellent biocompatibility, and sensitivity to specific stimulation. Herein, a simple and effective strategy of one-pot laser-induced emulsion polymerization at 532 nm was developed to prepare carmofur-loaded nanogels based on biocompatible and temperature/pH-sensitive monomers including polyethylene glycol diacrylate (PEGDA), N-vinylcaprolactam (NVCL), and 2-(dimethylamino) ethyl methacrylate (DMAEMA). The nanogels loading carmofur with dual-stimuli responsive drug release properties were rapidly obtained under laser irradiation (beam diameter 2.5 mm, laser power 60 mW) for only 100 s. These nanogels exhibited an average hydrodynamic diameter of 195.9 nm and a low polydispersity index of 0.115. The effect of monomer ratio on the size, morphology, double-bond conversion, and thermo/pH-sensitivity of nanogels was investigated. The cumulative carmofur release from nanogels at pH 5.0 within 48 h was nearly three times that at pH 7.4, while the release amount at 42 °C was twice that at 25 °C, showing the controlled and sustainable release with the change of pH and temperature. The in vitro release kinetics of carmofur was in accord with first-order release model.

Nanogels loading curcumin in situ through microemulsion photopolymerization for enhancement of antitumor effects.

Drug-loaded nanogels for cancer treatment can limit the free diffusion and distribution of drug molecules in the whole body to reduce undesirable side effects and improve the drug absorption efficiency of the tumor. In this study, curcumin as a model drug was encapsulated into nanogels in situ through microemulsion photopolymerization at 532 nm. Nanogels loaded with curcumin (NG-C) displayed a diameter of around 150 nm with good stability and a low polydispersity index of around 0.1. NG-C had a drug-loading capacity of 8.96 ± 1.16 wt%. The cumulative release of curcumin from NG-C was around 25%, 34% and 55% within 90 h in pH 7.4, 6.8 and 5.0 PBS buffer, respectively. NG-C presented prominent cytotoxicity toward Hep G2 and HeLa cancer cells in vitro. Moreover, NG-C exhibited much a stronger inhibition of tumor growth, necrosis, apoptosis, and the suppression of proliferation compared with curcumin on Hep G2 tumor-bearing nude mice.

Design and Applications of Tumor Microenvironment-Responsive Nanogels as Drug Carriers.

In recent years, the exploration of tumor microenvironment has provided a new approach for tumor treatment. More and more researches are devoted to designing tumor microenvironment-responsive nanogels loaded with therapeutic drugs. Compared with other drug carriers, nanogel has shown great potential in improving the effect of chemotherapy, which is attributed to its stable size, superior hydrophilicity, excellent biocompatibility, and responsiveness to specific environment. This review primarily summarizes the common preparation techniques of nanogels (such as free radical polymerization, covalent cross-linking, and physical self-assembly) and loading ways of drug in nanogels (including physical encapsulation and chemical coupling) as well as the controlled drug release behaviors. Furthermore, the difficulties and prospects of nanogels as drug carriers are also briefly described.

Effects of different water management strategies on the stability of cadmium and copper immobilization by biochar in rice-wheat rotation system.

Chemical immobilization of heavy metals is a simple, low-cost, and environment-friendly technology for remediation of heavy metals contaminated soils. However, changes in environmental conditions, such as water management, acid deposition, temperature fluctuation, etc., might result in release of metal ions from the fixation sites, and the long-term stability of immobilization remediation is unclear. This study attempted to investigate the impact of water management strategies (wetting-drying cycle and dry cycle) on the stability of heavy metal immobilization by one-time application of biochar during 3 consecutive years of rice-wheat crop in Cu/Cd-contaminated soil. The transformation and accumulation of Cd and Cu in soil-crop system and the morphololgy and composition of biochar were analyzed. The results revealed that wetting-drying cycle and drying treatments reduced the contents of available Cd and Cu in soil by 15.9%-17.7% and 23.9%-31.5% and by 19.8%-62.7% and 16.1%-65.0%, as well as increased soil pH by 0.11-0.31 and 0.17-0.56, respectively. In the wetting-drying cycle treatment, biochar was more favorable for decrease in Cd and Cu accumulation in crop, when compared with that in dry treatment; however, the differences were insignificant in the subsequent years. Although the different water management strategies had no obvious effect on the soil total C, physicochemical analysis of the biochar collected after pot experiments indicated that the obvious structural decomposition of biochar in the drying treatment may have resulted in the release of heavy metals immobilized in biochar. These findings help in better understanding of the long-term immobilization mechanism of biochar in soil-plant system.

A novel cross-linked nanoparticle with aggregation-induced emission properties for cancer cell imaging.

Fluorescent probes have been widely used in bioimaging as an efficient and convenient analytical tool. From the initial inorganic nanoparticles and small organic molecules to polymeric nanoparticles, scientific researchers have been trying to develop a probe with strong fluorescence and excellent biocompatibility. In this study, a tetraphenylethylene derivative with AIE properties and hyaluronic acid modified by methacrylic anhydride were combined to prepare a novel nanoparticle (HA-Ac-Pha-C) as a fluorescent probe by a photochemical cross-linking reaction. The fluorescence intensity and size of the nanoparticles were characterized by different techniques. It was confirmed that cross-linked nanoparticles not only showed stronger fluorescence, but also had better photostability while still maintaining 85.9% of the initial intensity after seven days. Moreover, cells and zebrafish imaging experiments also demonstrated that nanoparticles show specific fluorescence labeling for cancer cells and excellent biocompatibility in living organisms.

Hyaluronic Acid-Modified Fluorescent Probe for Dual Color Imaging of Living Cell.

Nanoprobes with biocompatibility and strong fluorescence have unique advantages in tumor detection and diagnosis. A nanoparticle with dual fluorescent signals for detecting and imaging of tumor cells was prepared, in which the outer layer of the particle is a hyaluronic acid-modified molecule with aggregation-induced emission properties, and the inner content is the boron-dipyrromethene (BODIPY) derivative. This nanoparticle has low critical micelle concentration, small size, and high fluorescence intensity. Cell imaging experiments showed that it is capable of stable cell imaging with a red and blue fluorescence conversion in response to cancer cells. Furthermore, the zebrafish experiment confirmed that it can be used for biological imaging. Nanoparticles with dual fluorescence response properties of the coated structure provide an effective way for detecting cancer cells.

Efficient removal of ethidium bromide from aqueous solution by using DNA-loaded Fe3O4 nanoparticles.

Ethidium bromide (EtBr) is widely used as DNA-staining dyes for the detection of nucleic acids in laboratories and known to be powerful mutagens and carcinogens. In the present paper, the removal of EtBr from aqueous solutions in a batch system using DNA-loaded Fe3O4 nanoparticles as a simple and efficient method was investigated. DNA was covalently loaded on the surface of Fe3O4 magnetic nanoparticles, which was confirmed by FT-IR analysis and zeta potential measurements. The morphology and crystal structure were characterized by SEM, TEM, and XRD. The influence factors on the removal efficiency such as initial EtBr concentration, contact time, adsorbent dose, pH, and temperature were also studied. The removal process of EtBr can be completed quickly within 1 min. The removal efficiency was more than 99% while the EtBr concentration was routinely used (0.5 mg L-1) in biology laboratories and the dosages of nanoparticles were 1 g L-1. For the different EtBr concentrations from 0.5 to 10 mg L-1 in aqueous solution, the goal of optimized removal was achieved by adjusting the dosage of DNA-loaded Fe3O4 nanoparticles. The optimum pH was around 7 and the operational temperature from 4 to 35 °C was appropriate. Kinetic studies confirmed that the adsorption followed second-order reaction kinetics. Thermodynamic data revealed that the process was spontaneous and exothermic. The adsorption of EtBr on DNA-loaded Fe3O4 nanoparticles fitted well with the Freundlich isotherm model. These results indicated that DNA-loaded Fe3O4 nanoparticles are a promising adsorbent for highly efficient removal of EtBr from aqueous solution in practice.

Injectable and self-healing polysaccharide-based hydrogel for pH-responsive drug release.

Injectable hydrogels with self-healing and pH-responsive property are appealing for biomedical applications. Herein, we developed a facile and green method to prepare a multifunctional polysaccharide-based hydrogel as a new carrier of drug. The hydrogels were prepared by forming reversible chemical bond between carboxyethyl-modified chitosan (CEC) and aldehyde modified hyaluronic acid (A-HA). The morphology and rheological property of the hydrogels with different solid content were systematically characterized. Owing to the dynamic equilibrium of the Schiff base bonds between amine groups on CEC and aldehyde groups on A-HA, the rapid self-healing performance of hydrogels was confirmed through qualitative and quantitative methods without any external stimulus. The pH-responsive behaviour was demonstrated by equilibrium swelling and in vitro Doxorubicin (Dox) release in PBS medium with various pH. In acidic condition, Dox can be release more rapidly compared with weak alkaline medium. Furthermore, the kill effect of Dox released from hydrogels for cancer cells was investigated. In vitro degradation and cytotoxicity examinations showed that the hydrogel is biodegradable and biocompatible. Therefore, such polysaccharide-based injectable self-healing and pH-responsive hydrogel is a promising candidate as drug delivery carrier.

Inhibition of proteases activity in intestine needs a sustainable acidic environment rather than a transient.

α-Chymotrypsin (α-CT) and trypsin are important components of the enzymatic barrier. They could degrade the therapeutic proteins and peptides, inhibit their activity consequently, and thereby reduce their oral bioavailability. Acidic agents, as one type of indirect protease inhibitors, have shown proof of concept in clinical trials. We report here the inactivated proteases due to acid influence can be reactivated immediately by environmental pH recovery regardless of how long the inactivation last. To keep the inactivation time of proteases for 4-5 h, we designed and prepared a sustained-release tablet containing citric acid (CA) which can effectively reduce the pH below 5.0 and maintain it for 5 h in the dissolution-reaction medium. The activity of α-CT and trypsin was quantified by analyzing the residual amount of their respective substrates BTEE and TAME. More than 80% of the substrates were survived in 5.0 h of incubation, whereas the common tablet inhibited the proteases activity for only two hours in the same experimental medium. It indicates that the sustained-release tablet loaded with CA can efficiently inhibit the α-CT and trypsin activity longer than the common tablet. The results will be beneficial for designing and formulating the peroral administration of peptide and protein drugs.

Structural influence of graft and block polycations on the adsorption of BSA.

Protein adsorption is considered as an important factor for the low transfection efficiency of polycations in vivo. In this study, two typical polycations of equal molecular weight with different structures were chosen to investigate their adsorption on bovine serum albumin (BSA), including the block copolymer named poly (N-vinylpyrrolidone)-b-poly (2-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA, i.e. PbP) and graft copolymer named PVP-g-PDMAEMA (PgP), respectively. Fluorescence spectroscopy was used to confirm the binding constants and binding sites between polycations and BSA in static state. The binding constants were 4.1×10(4)M(-1) vs 8.3×10(4)M(-1) and binding sites were 0.3 vs 1.1 for PbP and PgP, respectively, indicating PgP had stronger binding affinity with BSA. Surface plasmon resonance (SPR) was used to study the dynamical non-specific interaction between BSA and polycations as well as the polyplexes. The numbers of both PbP and PgP adsorbed on BSA increased with concentration of polycations increasing, and the number of PgP adsorbed on BSA is higher compared with PbP when their concentration is low. When their concentration is high, the number of PbP adsorbed on BSA is more than that of PgP. However, PgP/DNA polyplexes showed higher adsorption amount compared with PbP/DNA polyplexes at different N/P ratios.

Polycations with excellent gene transfection ability based on PVP-g-PDMAEMA with random coil and micelle structures as non-viral gene vectors.

The low transfection efficiency of polycations is still a major problem for successful gene therapy. To address this issue, in this study, hydrophilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate] (PVP-g-PDMAEMA) and amphiphilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate]-block-poly(methylmethacrylate) (PVP-g-PDMAEMA-b-PMMA) were synthesized via the atom transfer radical polymerization (ATRP) method, and their properties as gene vectors were investigated subsequently. PVP-g-PDMAEMA formed random coils in water and PVP-g-PDMAEMA-b-PMMA self-assembled into spherical core-shell micelles with a very low critical micelle concentration of only 6.3 × 10-3 mg mL-1. PVP-g-PDMAEMA-b-PMMA/pDNA polyplexes demonstrated an excellent gene transfection efficiency, which showed not only much higher gene transfection efficiency than PVP-g-PDMAEMA/pDNA polyplexes, but obviously surpassed 25k PEI at low N/P ratio around 3 on 293T cell lines. Hence, the results suggested that PVP-g-PDMAEMA-b-PMMA could be a highly efficient gene vector.

Modified bovine serum albumin as an effective charge-reversal platform for simultaneously improving the transfection efficiency and biocompatibility of polyplexes.

The charge-reversal strategy is usually employed in gene delivery to facilitate the endosomal escape of gene carriers and the release of the payload into cytoplasm. However, most of the charge-reversal materials are far from perfect biocompatible materials due to the cytotoxicity of themselves or their hydrolyzed products. In this study, an excellent charge-reversal material named modified bovine serum albumin (mBSA) was prepared. The charge reversal of biocompatible mBSA is a physical process and can instantly occur, which was confirmed by zeta potential, size detection and morphological studies. The introduction of mBSA can not only reduce the zeta potential of binary complexes (pDNA-PEI) but also increase the nuclease resistance ability of the pDNA-PEI binary complexes. In addition, cell viabilities tested by MTT assay and gene transfection assay demonstrated that mBSA can reduce the cytotoxicity of pDNA-PEI polyplexes and improve their gene transfection efficiency (serum free and 10% FBS medium) both in 293T and HepG2 cells at the same time. The experimental results of cell internalization and intracellular distribution of pDNA-PEI-mBSA ternary complexes confirmed that the improvement of transfection efficiency originated from the enhancement of endosomal escape of polyplexes. Therefore, mBSA has been proven to be a perfect charge-reversal platform to simultaneously improve the transfection efficiency and biocompatibility of polyplexes.

Structural impact of graft and block copolymers based on poly(N-vinylpyrrolidone) and poly(2-dimethylaminoethyl methacrylate) in gene delivery.

Cationic polymers (polycations) are promising gene vectors that are conveniently synthesized and easily modified. In order to study the relationship between structures and properties of the polycations in gene delivery, a graft copolymer called poly(N-vinylpyrrolidone)-g-poly(2-dimethylaminoethyl methacrylate) (PVP-g-PDMAEMA, i.e. PgP) and a block copolymer called PVP-b-PDMAEMA (PbP) with equal molecular weight of PDMAEMA and PVP were prepared by two advanced living radical polymerization reactions including atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) techniques. Compared with PbP, PgP could condense pDNA more effectively into polyplexes with smaller size, higher zeta potential and better stability. The transfection efficiency of PgP at a low N/P ratio of 4 : 1 was not only higher than that of PbP, but also much higher than that of the commercially available PEI as the gold standard of polycations and lipofectamine. In addition, both PgP and PbP had less BSA absorption compared with PEI, indicating that PVP could resist BSA absorption. In order to understand the mechanism behind the high transfection efficiency of PgP, cellular uptake and endosomal escape of PgP/pDNA and PbP/pDNA polyplexes were investigated. The results demonstrated that the improvement of the transfection efficiency of PgP originated from the promotion of the cellular uptake and endosome/lysosome escape. This study will provide useful information on designing effective non-viral vectors for gene delivery.

3D hydrogels with high resolution fabricated by two-photon polymerization with sensitive water soluble initiators.

Hydrogels with precise 3D configuration (3D hydrogels) are crucial for biomedical applications such as tissue engineering and drug delivery, which require the improvement of the spatial resolution on both the microscopic and the nanometric scale. In this study, a water soluble two-photon polymerization (TPP) initiator (WI) with high initiating efficiency was prepared by using a poloxamer (PF127) to encapsulate 2,7-bis(2-(4-pentaneoxy-phenyl)-vinyl)anthraquinone via a hydrophilic-hydrophobic assembly. The threshold energy for WI was 6.29 mW at a linear scanning speed of 10 µm s-1, which was much lower than those reported previously. A lateral spatial resolution of 92 nm was achieved as the resolution breakthrough of 3D hydrogels. Finally, the microstructure with high accuracy simulating the morphology of adenovirus was fabricated at the laser power close to the threshold energy of TPP, further demonstrating the ultrahigh resolution of 3D hydrogels.

Ternary complexes of poly(vinyl pyrrolidone)-graft-poly(2-dimethylaminoethyl methacrylate), DNA and bovine serum albumin for gene delivery.

Novel well-defined hydrophilic cationic polymers with different length of polycation chain for gene delivery, poly(vinyl pyrrolidone)-graft-poly(2-dimethylaminoethyl methacrylate)s (PPDs), were synthesized by atom transfer radical polymerization (ATRP). The chemical structures and compositions of these polymers were characterized by FT-IR, (1)H-NMR and GPC. The experimental results of dynamic light scattering (DLS), ζ-potential and transmission electron microscopy (TEM) indicated that PPD could condense plasmid DNA (pDNA) to form nanocomplexes. Agarose gel retardation assays demonstrated that PPD could encapsulate plasmid DNA completely when the N/P ratio is equal to or above 3. MTT assay and in vitro gene transfection results indicated that PPD/pDNA complexes exhibited high transfection efficiency concomitant with obvious cytotoxicity. Furthermore, bovine serum albumin (BSA) was utilized to assembly with the binary complexes of PPD/pDNA to screen the residual surface positive charges of complexes in order to decrease cytotoxicity of the binary complexes. Physicochemical properties were characterized and the results indicated that the coating of BSA was able to decrease the zeta potential of the nano-sized PPD/pDNA complexes nearly to electroneutrality without interfering with DNA condensation ability. The ternary complexes of BSA/PPD/pDNA demonstrated no cytotoxicity and also maintained high gene transfection efficiency in HepG2 cells in 10% serum compared with that in serum-free condition.

Binary and ternary complexes based on polycaprolactone-graft-poly (N, N-dimethylaminoethyl methacrylate) for targeted siRNA delivery.

Small interfering RNA (siRNA) is a powerful gene silencing tool and has promising prospects in basic research and the development of therapeutic reagents. However, the lack of an effective and safe tool for siRNA delivery hampers its application. Here, we introduced binary and ternary complexes that effectively mediated siRNA-targeted gene silencing. Both complexes showed excellent siRNA loading even at the low N/P/C ratio of 3:1:0. FACS and confocal microscopy demonstrated that nearly all cells robustly internalized siRNAs into the cytoplasm, where RNA interference (RNAi) occurred. Luciferase assay and Western blot verified that silencing efficacy reached >80%, and introducing folate onto the ternary complexes further enhanced silencing efficacy by about 10% over those without folate at the same N/P/C ratio. In addition, the coating of PGA-g-mPEG decreased the zeta potential almost to electroneutrality, and the MTT assay showed decreased cytotoxicity. In vivo distribution measurement and histochemical analysis executed in C57BL/6 and Hela tumor-bearing BALB/c nude mice showed that complexes accumulated in the liver, lungs, pancreas and tumors and were released slowly for a long time after intravenous injection. Furthermore, ternary complexes showed higher siRNA fluorescence intensity than binary complexes at the same N/P ratio in tumor tissues, those with folate delivered more siRNAs to tumors than those without folate, and more folate induced more siRNA transport to tumors. In addition, in vivo functional study showed that both binary and ternary complexes mediated down-regulation of ApoB in liver efficiently and consequently blocked the secretion of fatty acids into the blood, resulted in lipid accumulation in liver, liver steatosis and hepatic dysfunction. In conclusion, these complexes provided a powerful means of administration for siRNA-mediated treatment of liver-related diseases and various cancers, especial for pancreatic and cervical cancer.