Comparison of two methods for tumour-targeting peptide modification of liposomes.

Liposomes decorated with tumour-targeting cell-penetrating peptides can enhance specific drug delivery at the tumour site. The TR peptide, c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL, is pH-sensitive and actively targets tumour cells that overexpress integrin receptor αvß3, such as B16F10 melanoma cells. Liposomes can be modified with the TR peptide by two different methods: utilization of the cysteine residue on TR to link DSPE-PEG2000-Mal contained in the liposome formula (LIPTR) or decoration of TR with a C18 stearyl chain (C18-TR) for direct insertion into the liposomal phospholipid bilayer through electrostatic and hydrophobic interactions (LIPC18-TR). We found that both TR and C18-TR effectively reversed the surface charge of the liposomes when the systems encountered the low pH of the tumour microenvironment, but LIPC18-TR exhibited a greater increase in the charge, which led to higher cellular uptake efficiency. Correspondingly, the IC50 values of PTX-LIPTR and PTX-LIPC18-TR in B16F10 cells in vitro were 2.1-fold and 2.5-fold lower than that of the unmodified PTX-loaded liposomes (PTX-LIP), respectively, in an acidic microenvironment (pH 6.3). In B16F10 tumour-bearing mice, intravenous administration of PTX-LIPTR and PTX-LIPC18-TR (8 mg/kg PTX every other day for a total of 4 injections) caused tumour reduction ratios of 39.4% and 56.1%, respectively, compared to 20.8% after PTX-LIP administration. Thus, we demonstrated that TR peptide modification could improve the antitumour efficiency of liposomal delivery systems, with C18-TR presenting significantly better results. After investigating different modification methods, our data show that selecting an adequate method is vital even when the same molecule is used for decoration.

Tool Frame Calibration for Robot-Assisted Ultrasonic Testing.

Tool frame calibration has been widely used in robot-assisted printing, welding, and grinding, but it is not suitable for ultrasonic testing because the robot is submerged in water. The purpose of this paper is to present a tool frame calibration method, which is suitable for improving the precision of ultrasonic testing. In uniform mediums, sound travels along a straight line like ray. A reflector is fixed in water to reflect ultrasound, which makes it possible to measure distances between incidence points on a reflector and tool center point (TCP) on an ultrasound transducer. In addition, the positions and poses of the end flange are recorded through a robot controller. Finally, an optimization method is applied to calculate the position and pose errors of the tool frame relative to the end flange according to such records. The presented method was implemented in an ultrasonic testing system. We selected 100 incidence points on the reflector to calculate the assembly errors of the transducer. The pulse amplitude rose obviously after calibration, which verifies that this is an effective method. Considering that ultrasonic transducers can be used as a measuring tool, this paper proposes a tool frame calibration method for ultrasonic testing robots without introducing other measuring devices, which draws the conclusion that tool frame can be calibrated through ultrasound.

Rational Design of a Targetable Fluorescent Probe for Visualizing H2S Production under Golgi Stress Response Elicited by Monensin.

As a eukaryotic organelle, the Golgi apparatus plays an essential role in various physiological activities such as stress response. The Golgi stress response is an important physiological process of conferring cytoprotection by regulating the synthesis and metabolism of bioactive molecules. Therefore, the development of new suitable in situ analytical techniques for monitoring related small molecular substances in the stress reaction of the Golgi apparatus is very helpful for further study of the regulatory mechanism of the Golgi apparatus. Recent studies have shown that endogenous hydrogen sulfide (H2S) also possesses crucial bioregulatory and protective performances in the stress response. Therefore, the high-fidelity in situ mapping of H2S production under the Golgi stress response plays an important role not only in revealing cytoprotection functions of H2S in the stress response but also in further understanding the regulatory mechanism of the Golgi stress response. In this work, we designed a simple Golgi-targetable H2S fluorescent probe (Gol-H2S) that responds accurately and sensitively to H2S in the Golgi apparatus of living cells and zebrafish. On the basis of its superior bioimaging performances, probe Gol-H2S was successfully applied to the in situ visualization of H2S production under the Golgi stress response elicited by monensin, a specific-Golgi stressor. The related process of the Golgi stress response was validated by stimulation and inhibition experiments. These findings fully demonstrate that H2S is an alternative biomarker of the Golgi stress response. Moreover, probe Gol-H2S can also be used as a potential tool for disclosing the detailed H2S-cytoprotection mechanisms under the regulation of the Golgi stress response in related diseases.

Local Targeting of Lung-Tumor-Associated Macrophages with Pulmonary Delivery of a CSF-1R Inhibitor for the Treatment of Breast Cancer Lung Metastases.

The lungs are major sites of metastases for several cancer types, including breast cancer (BC). Prognosis and quality of life of BC patients that develop pulmonary metastases are negatively impacted. The development of strategies to slow the growth and relieve the symptoms of BC lung metastases (BCLM) is thus an important goal in the management of BC. However, systemically administered first line small molecule chemotherapeutics have poor pharmacokinetic profiles and biodistribution to the lungs and significant off-target toxicity, severely compromising their effectiveness. In this work, we propose the local delivery of add-on immunotherapy to the lungs to support first line chemotherapy treatment of advanced BC. In a syngeneic murine model of BCLM, we show that local pulmonary administration (p.a.) of PLX-3397 (PLX), a colony-stimulating factor 1 receptor inhibitor (CSF-1Ri), is capable of overcoming physiological barriers of the lung epithelium, penetrating the tumor microenvironment (TME), and decreasing phosphorylation of CSF-1 receptors, as shown by the Western blot of lung tumor nodules. That inhibition is accompanied by an overall decrease in the abundance of protumorigenic (M2-like) macrophages in the TME, with a concomitant increase in the amount of antitumor (M1-like) macrophages when compared to the vehicle-treated control. These effects with PLX (p.a.) were achieved using a much smaller dose (1 mg/kg, every other day) compared to the systemic doses typically used in preclinical studies (40-800 mg/kg/day). As an additive in combination with intravenous (i.v.) administration of paclitaxel (PTX), PLX (p.a.) leads to a decrease in tumor burden without additional toxicity. These results suggested that the proposed immunochemotherapy, with regional pulmonary delivery of PLX along with the i.v. standard of care chemotherapy, may lead to new opportunities to improve treatment, quality of life, and survival of patients with BCLM.

A novel highly sensitive fluorescent probe for bioimaging biothiols and its applications in distinguishing cancer cells from normal cells.

In recent years, targeting drugs made by physical loading or chemical bonding of drugs on small molecular carriers have shown a very wide application prospect in the field of tumor and cancer treatment. How to achieve the release of drugs in cancer cells has become the core of this research. One of the most important bases for drug localization is to use the difference of small molecular biothiol concentration between cancer cells and normal cells. Details of the changes of biothiol levels in the growth and reproduction of cancer cells are still poorly understood, and the main reason is the lack of sensitive real-time imaging tools for biothiols in cancer cells. In this work, we reasonably designed and synthesized the combination of 4-hydroxy-1,8-naphthalimide and NBD-Cl as a concise fluorescent probe HN-NBD for imaging biothiols in live cells and zebrafish. In addition, due to the advantages of HN-NBD design, it is sufficiently sensitive to biothiols, and further imaging can distinguish cancer cells from normal cells. Probe HN-NBD would be of great significance to biomedical researchers for the study of biothiol-related diseases, the screening of new anticancer drugs, and the early diagnosis and treatment of cancers.

A simple highly specific fluorescent probe for simultaneous discrimination of cysteine/homocysteine and glutathione/hydrogen sulfide in living cells and zebrafish using two separated fluorescence channels under single wavelength excitation.

Biothiols such as cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and hydrogen sulfide (H2S) are widely found in mammalian cells. They are closely related to the production and metabolic pathways and play very important roles in physiological and pathological activities. Therefore, the quantitative detection of these biothiols is of great significance. Although many fluorescent probes have been successfully used to track biothiols in biological samples, the fluorescence method for simultaneously detecting these biothiols using separated fluorescence emission channels under single wavelength excitation is still immature. In this work, we prepared the conjugate of seminaphthorhodafluor (SNARF) dye and 7-nitro-1,2,3-benzoxadiazole (NBD) using as a simple long-wavelength fluorescent probe SNARF-NBD for specific detection of biothiols. Cys/Hcy and GSH/H2S were identified by two separated fluorescence emission channels under single wavelength excitation, which showed good selectivity and sensitivity. In addition, SNARF-NBD has low cytotoxicity and shows good imaging ability in living cells and zebrafish.

Crack Assessment of Wheel Hubs via an Ultrasonic Transducer and Industrial Robot.

Crack assessment when making fitness-for-service decisions requires a thorough examination of crack location and size in critical areas. An ultrasonic transducer is used for such assessments, but traditional methods cannot cope with complex rotators, such as wheel hubs. We present a model of robot-assisted crack growth assessment in wheel hubs. We integrate a six-degrees-of-freedom (DOF) industrial robot and a turntable to form a robot-assisted ultrasonic testing (UT) system that does not use traditional UT equipment. Ultrasonic beams are focused at certain depths appropriate for achieving maximum sensitivity. We quantitatively analysed wheel hubs with longitudinal and transverse series of pre-cracks, and concluded that our system autonomously detected cracks.

TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux.

Insufficient lysosomal removal of autophagic cargoes in cardiomyocytes has been suggested as a main cause for the impairment of the autophagic-lysosomal pathway (ALP) in many forms of heart disease including cardiac proteinopathy and may play an important pathogenic role; however, the molecular basis and the correcting strategy for the cardiac ALP insufficiency require further investigation. The present study was sought to determine whether myocardial expression and activity of TFEB, the recently identified ALP master regulator, are impaired in a cardiac proteinopathy mouse model and to determine the effect of genetic manipulation of TFEB expression on autophagy and proteotoxicity in a cardiomyocyte model of proteinopathy. We found that increased myocardial TFEB mRNA levels and a TFEB protein isoform switch were associated with marked decreases in the mRNA levels of representative TFEB target genes and increased mTORC1 activation, in mice with cardiac transgenic expression of a missense (R120G) mutant αB-crystallin (CryABR120G), a well-established model of cardiac proteinopathy. Using neonatal rat ventricular cardiomyocyte cultures, we demonstrated that downregulation of TFEB decreased autophagic flux in cardiomyocytes both at baseline and during CryABR120G overexpression and increased CryABR120G protein aggregates. Conversely, forced TFEB overexpression increased autophagic flux and remarkably attenuated the CryABR120G overexpression-induced accumulation of ubiquitinated proteins, caspase 3 cleavage, LDH leakage, and decreases in cell viability. Moreover, these protective effects of TFEB were dramatically diminished by inhibiting autophagy. We conclude that myocardial TFEB signaling is impaired in cardiac proteinopathy and forced TFEB overexpression protects against proteotoxicity in cardiomyocytes through improving ALP activity.

COP9 signalosome controls the degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity.

RATIONALE: Impaired degradation of misfolded proteins is associated with a large subset of heart diseases. Misfolded proteins are degraded primarily by the ubiquitin-proteasome system, but the ubiquitin ligases responsible for the degradation remain largely unidentified. The cullin deneddylation activity of the COP9 signalosome (CSN) requires all 8 CSN subunits (CSN1 through CSN8) and regulates cullin-RING ligases, thereby controlling ubiquitination of a large number of proteins; however, neither CSN nor cullin-RING ligases is known to regulate the degradation of cytosolic misfolded proteins. OBJECTIVE: We sought to investigate the role of CSN8/CSN in misfolded protein degradation and cardiac proteinopathy. METHODS AND RESULTS: Cardiac CSN8 knockout causes mouse premature death; hence, CSN8 hypomorphism (CSN8(hypo)) mice were used. Myocardial neddylated forms of cullins were markedly increased, and myocardial capacity of degrading a surrogate misfolded protein was significantly reduced by CSN8 hypomorphism. When introduced into proteinopathic mice in which a bona fide misfolded protein R120G missense mutation of αß-crystallin (CryAB(R120G)) is overexpressed in the heart, CSN8 hypomorphism aggravated CryAB(R120G)-induced restrictive cardiomyopathy and shortened the lifespan of CryAB(R120G) mice, which was associated with augmented accumulation of protein aggregates, increased neddylated proteins, and reduced levels of total ubiquitinated proteins and LC3-II in the heart. In cultured cardiomyocytes, both CSN8 knockdown and cullin-RING ligase inactivation suppressed the ubiquitination and degradation of CryAB(R120G) but not native CryAB, resulting in accumulation of protein aggregates and exacerbation of CryAB(R120G) cytotoxicity. CONCLUSIONS: (1) CSN8/CSN promotes the ubiquitination and degradation of misfolded proteins and protects against cardiac proteotoxicity, and (2) cullin-RING ligases participate in degradation of cytosolic misfolded proteins.

A weighted difference of L1 and L2 on the gradient minimization based on alternating direction method for circular computed tomography.

Iterative reconstruction algorithms for computed tomography (CT) through total variation (TV) regularization can provide accurate and stable reconstruction results. TV minimization is the L1-norm of gradient-magnitude images and can be regarded as a convex relaxation method to replace the L0 norm. In this study, a fast and efficient algorithm, which is named a weighted difference of L1 and L2 (L1 - αL2) on the gradient minimization, was proposed and investigated. The new algorithm provides a better description of sparsity for the optimization-based algorithms than TV minimization algorithms. The alternating direction method is an efficient method to solve the proposed model, which is utilized in this study. Both simulations and real CT projections were tested to verify the performances of the proposed algorithm. In the simulation experiments, the reconstructions from the proposed method provided better image quality than TV minimization algorithms with only 7 views in 180 degrees, which is also computationally faster. Meanwhile, the new algorithm enabled to achieve the final solution with less iteration numbers.

Optimization-based image reconstruction in computed tomography by alternating direction method with ordered subsets.

Nowadays, diversities of task-specific applications for computed tomography (CT) have already proposed multiple challenges for algorithm design of image reconstructions. Consequently, efficient algorithm design tool is necessary to be established. A fast and efficient algorithm design framework for CT image reconstruction, which is based on alternating direction method (ADM) with ordered subsets (OS), is proposed, termed as OS-ADM. The general ideas of ADM and OS have been abstractly introduced and then they are combined for solving convex optimizations in CT image reconstruction. Standard procedures are concluded for algorithm design which contain 1) model mapping, 2) sub-problem dividing and 3) solving, 4) OS level setting and 5) algorithm evaluation. Typical reconstruction problems are modeled as convex optimizations, including (non-negative) least-square, constrained L1 minimization, constrained total variation (TV) minimization and TV minimizations with different data fidelity terms. Efficient working algorithms for these problems are derived with detailed derivations by the proposed framework. In addition, both simulations and real CT projections are tested to verify the performances of two TV-based algorithms. Experimental investigations indicate that these algorithms are of the state-of-the-art performances. The algorithm instances show that the proposed OS-ADM framework is promising for practical applications.

A two-step filtering-based iterative image reconstruction method for interior tomography.

The optimization-based method that utilizes the additional sparse prior of region-of-interest (ROI) image, such as total variation, has been the subject of considerable research in problems of interior tomography reconstruction. One challenge for optimization-based iterative ROI image reconstruction is to build the relationship between ROI image and truncated projection data. When the reconstruction support region is smaller than the original object, an unsuitable representation of data fidelity may lead to bright truncation artifacts in the boundary region of field of view. In this work, we aim to develop an iterative reconstruction method to suppress the truncation artifacts and improve the image quality for direct ROI image reconstruction. A novel reconstruction approach is proposed based on an optimization problem involving a two-step filtering-based data fidelity. Data filtering is achieved in two steps: the first takes the derivative of projection data; in the second step, Hilbert filtering is applied in the differentiated data. Numerical simulations and real data reconstructions have been conducted to validate the new reconstruction method. Both qualitative and quantitative results indicate that, as theoretically expected, the proposed method brings reasonable performance in suppressing truncation artifacts and preserving detailed features. The presented local reconstruction method based on the two-step filtering strategy provides a simple and efficient approach for the iterative reconstruction from truncated projections.

Enantioselective N-heterocyclic carbene-catalyzed synthesis of indenopyrones.

The chiral N-heterocyclic carbene-catalyzed [4 + 2] cyclization of α-chloroaldehydes and arylidene indanediones was developed, giving the corresponding indenopyrones in good yields with high diastereoselectivities and enantioselectivities.

Efficient and robust 3D CT image reconstruction based on total generalized variation regularization using the alternating direction method.

Iterative reconstruction algorithms for computed tomography (CT) through total variation regularization based on piecewise constant assumption can produce accurate, robust, and stable results. Nonetheless, this approach is often subject to staircase artefacts and the loss of fine details. To overcome these shortcomings, we introduce a family of novel image regularization penalties called total generalized variation (TGV) for the effective production of high-quality images from incomplete or noisy projection data for 3D reconstruction. We propose a new, fast alternating direction minimization algorithm to solve CT image reconstruction problems through TGV regularization. Based on the theory of sparse-view image reconstruction and the framework of augmented Lagrange function method, the TGV regularization term has been introduced in the computed tomography and is transformed into three independent variables of the optimization problem by introducing auxiliary variables. This new algorithm applies a local linearization and proximity technique to make the FFT-based calculation of the analytical solutions in the frequency domain feasible, thereby significantly reducing the complexity of the algorithm. Experiments with various 3D datasets corresponding to incomplete projection data demonstrate the advantage of our proposed algorithm in terms of preserving fine details and overcoming the staircase effect. The computation cost also suggests that the proposed algorithm is applicable to and is effective for CBCT imaging. Theoretical and technical optimization should be investigated carefully in terms of both computation efficiency and high resolution of this algorithm in application-oriented research.

System matrix analysis for sparse-view iterative image reconstruction in X-ray CT.

Iterative image reconstruction (IIR) with sparsity-exploiting methods, such as total variation (TV) minimization, used for investigations in compressive sensing (CS) claim potentially large reductions in sampling requirements. Quantifying this claim for computed tomography (CT) is non-trivial, as both the singularity of undersampled reconstruction and the sufficient view number for sparse-view reconstruction are ill-defined. In this paper, the singular value decomposition method is used to study the condition number and singularity of the system matrix and the regularized matrix. An estimation method of the empirical lower bound is proposed, which is helpful for estimating the number of projection views required for exact reconstruction. Simulation studies show that the singularity of the system matrices for different projection views is effectively reduced by regularization. Computing the condition number of a regularized matrix is necessary to provide a reference for evaluating the singularity and recovery potential of reconstruction algorithms using regularization. The empirical lower bound is helpful for estimating the projections view number with a sparse reconstruction algorithm.

Distributed CT image reconstruction algorithm based on the alternating direction method.

With the development of compressive sensing theory, image reconstruction from few-view projections has been paid considerable research attention in the field of computed tomography (CT). Total variation (TV)-based CT image reconstruction has been shown experimentally to be capable of producing accurate reconstructions from sparse-view data. Motivated by the need of solving few-view reconstruction problem with large scale data, a general block distribution reconstruction algorithm based on TV minimization and the alternating direction method (ADM) has been developed in this study. By utilizing the inexact ADM, which involves linearization and proximal point techniques, the algorithm is relatively simple and hence convenient for the derivation and distributed implementation. And because the data as well as the computation are distributed to individual nodes, an outstanding acceleration factor is achieved. Experimental results demonstrate that the proposed method can accelerate the alternating direction total variation minimization (ADTVM) algorithm with nearly no loss of accuracy, which means compared with ADTVM, the proposed algorithm has a better accuracy with same running time.

Edge guided image reconstruction in linear scan CT by weighted alternating direction TV minimization.

Linear scan computed tomography (CT) is a promising imaging configuration with high scanning efficiency while the data set is under-sampled and angularly limited for which high quality image reconstruction is challenging. In this work, an edge guided total variation minimization reconstruction (EGTVM) algorithm is developed in dealing with this problem. The proposed method is modeled on the combination of total variation (TV) regularization and iterative edge detection strategy. In the proposed method, the edge weights of intermediate reconstructions are incorporated into the TV objective function. The optimization is efficiently solved by applying alternating direction method of multipliers. A prudential and conservative edge detection strategy proposed in this paper can obtain the true edges while restricting the errors within an acceptable degree. Based on the comparison on both simulation studies and real CT data set reconstructions, EGTVM provides comparable or even better quality compared to the non-edge guided reconstruction and adaptive steepest descent-projection onto convex sets method. With the utilization of weighted alternating direction TV minimization and edge detection, EGTVM achieves fast and robust convergence and reconstructs high quality image when applied in linear scan CT with under-sampled data set.

Effect of multi-interface electron transfer on water splitting and an innovative electrolytic cell for synergistic hydrogen production and degradation.

The cleaning and utilization of industry wastewater are still a big challenge. In this work, we mainly investigate the effect of electron transfer among multi-interfaces on water electrolysis reaction. Typically, the CoS2, Co3S4/CoS2 (designated as CS4-2) and Co3S4/Co9S8/CoS2 (designated as CS4-8-2) samples are prepared on a large scale by one-step molten salt method. It is found that because of the different work functions (designated as WF; WF(Co3S4) = 4.48eV, WF(CoS2) = 4.41eV, WF(Co9S8) = 4.18 eV), the effective heterojunctions at the multi-interfaces of CS4-8-2 sample, which obviously improve interface charge transfer. Thus, the CS4-8-2 sample shows an excellent oxygen evolution reaction (OER) activity (134 mV/10 mA cm-2, 40 mV dec-1). The larger double-layer capacitance (Cdl = 17.1 mF cm-2) of the CS4-8-2 sample indicates more electrochemical active sites, compared to the CoS2 and CS4-2 samples. Density functional theory (DFT) calculation proves that due to interface polarization under electric field, the multi-interfaces effectively promote electron transfer and regulate electron structure, thus promoting the adsorption of OH- and dissociation of H2O. Moreover, an innovative norfloxacin (NFX) electrolytic cell (EC) is developed through introducing NFX into the electrolyte, in which efficient NFX degradation and hydrogen production are synergistically achieved. To reach 50 mA cm-2, the required cell voltage of NFX-EC has decreased by 35.2%, compared to conventional KOH-EC. After 2h running at 1 V, 25.5% NFX was degraded in the NFX EC. This innovative NFX-EC is highly energy-efficient, which is promising for the synergistic cleaning and utilization of industry wastewater.

Regulating band structure, charge transfer and separation, oxygen adsorption and activation by surface ion modification.

As a most promising environmental technology, the substantial enhancement of photocatalytic efficiency is still a big challenge for practical applications. In this work, the surface of Bi2O2CO3 (BOC) nanotubes are modified by Cl and I. The as-obtained samples at different hydrothermal temperatures (T) are designated as T-X-BOC (X = Cl, I). X-ray diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy and X-ray photoelectron spectroscopy (XPS) prove that Cl and I merely chemically adsorb on the BOC surface, rather than dope into the crystal lattice. The surface modification of Cl and I slightly increases light absorption range, while significantly promotes the photoelectron migration from bulk to the surface that greatly enhances the carrier separation efficiency. Density functional theory (DFT) calculations further prove that surface Cl and I have adjusted band structure and surface charge distribution. Besides, the surface Cl and I favor the O2 adsorption and trap the surface photoelectrons, thus promoting the formation of •O2-; while the surface Cl and I impede the surface adsorption of H2O, thus refraining the generation of •OH. In the degradation of rhodamine B (RhB), holes and •O2- radicals play the crucial role. Under ultraviolet light irradiation (λ < 420 nm) for 45 min, the RhB degradation ratios over 150-Cl-BOC (94%) and 150-I-BOC (85%) are 4.2 and 3.7 times higher than that of original BOC (18%), respectively. This work demonstrates that the simple surface halogenation modification greatly improves the photocatalytic activity.

Replacing cholesterol with asiatic acid to prolong circulation and enhance anti-metastatic effects of non-PEGylated liposomes.

Cholesterol is an indispensable component of most liposomes, heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo. On the other hand, as an active ingredient, AA can decrease TGF-ß secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.