Efficacy and safety of VEGF/VEGFR inhibitors for platinum-resistant ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Almost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC. METHODS: A comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity. RESULTS: In total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62-0.84, p < 0.0001) and PFS (HR = 0.52; 95% CI: 0.45-0.59, p < 0.0001) demonstrated a significant prolongation in the combination group compared to chemotherapy alone for PROC. In addition, combination therapy demonstrated a superior ORR compared to monotherapy (OR = 2.34; 95%CI: 1.27-4.32, p < 0.0001). Subgroup analysis indicated that the combination treatment of VEGF/VEGFR inhibitors and chemotherapy was significantly more effective than monochemotherapy in terms of OS (HR = 0.71; 95% CI: 0.61-0.84, p < 0.0001), PFS (HR = 0.49; 95% CI: 0.42-0.57, p < 0.0001), and ORR (OR = 2.97; 95% CI: 1.89-4.67, p < 0.0001). Although the combination therapy was associated with higher incidences of hypertension, mucositis, proteinuria, diarrhea, and hand-foot syndrome compared to monochemotherapy, these toxicities were manageable and well-tolerated. CONCLUSIONS: The meta-analysis demonstrated that combination therapy with VEGF/VEGFR inhibitors yielded better clinical outcomes for patients with PROC compared to monochemotherapy, especially when combined with chemotherapy. This analysis provides more treatment options for patients with PROC. SYSTEMATIC REVIEW REGISTRATION: [ https://www.crd.york.ac.uk/PROSPERO ], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42023402050.

Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis.

Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different bleeding risks. Previous studies have shown that coagulation factor XI is an ideal target for safe anticoagulant drug development. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively. DX-88mut selectively inhibited FXIa against a panel of serine proteases with an IC50 value of 14.840 ± 0.453 nM, dose-dependently prolonged APTT in mouse, rat and human plasma, and potently inhibited FeCl3-induced carotid artery thrombosis in mice at a dose of 1 µmol/kg. Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5 µmol/kg. Taken together, these results show that DX-88mut is a potential candidate for the development of a novel antithrombotic agent.

Comparative Transcriptome Analysis of Galeruca daurica Reveals Cold Tolerance Mechanisms.

Galeruca daurica (Joannis) is a pest species with serious outbreaks in the Inner Mongolian grasslands in recent years, and its larvae and eggs are extremely cold-tolerant. To gain a deeper understanding of the molecular mechanism of its cold-tolerant stress response, we performed de novo transcriptome assembly of G. daurica via RNA-Seq and compared the differentially expressed genes (DEGs) of first- and second-instar larvae grown and developed indoors and outdoors, respectively. The results show that cold tolerance in G. daurica is associated with changes in gene expression mainly involved in the glycolysis/gluconeogenesis pathway, the fatty acid biosynthesis pathway and the production of heat shock proteins (HSPs). Compared with the control group (indoor), the genes associated with gluconeogenesis, fatty acid biosynthesis and HSP production were up-regulated in the larvae grown and developed outdoors. While the changes in these genes were related to the physiological metabolism and growth of insects, it was hypothesized that the proteins encoded by these genes play an important role in cold tolerance in insects. In addition, we also investigated the expression of genes related to the metabolic pathway of HSPs, and the results show that the HSP-related genes were significantly up-regulated in the larvae of G. daurica grown and developed outdoors compared with the indoor control group. Finally, we chose to induce significant expression differences in the Hsp70 gene (Hsp70A1, Hsp70-2 and Hsp70-3) via RNAi to further illustrate the role of heat stress proteins in cold tolerance on G. daurica larvae. The results show that separate and mixed injections of dsHSP70A1, dsHsp70-2 and dsHsp70-3 significantly reduced expression levels of the target genes in G. daurica larvae. The super-cooling point (SCP) and the body fluid freezing point (FP) of the test larvae were determined after RNAi using the thermocouple method, and it was found that silencing the Hsp70 genes significantly increased the SCP and FP of G. daurica larvae, which validated the role of heat shock proteins in the cold resistance of G. daurica larvae. Our findings provide an important theoretical basis for further excavating the key genes and proteins in response to extremely cold environments and analyzing the molecular mechanism of cold adaptation in insects in harsh environments.

Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Antitumor Activity of Disulfiram and Cisplatin in Ovarian Cancer.

INTRODUCTION: Among gynecological cancers, ovarian cancer has a high mortality rate. Cisplatin-based chemotherapy is commonly used for the treatment of ovarian cancer. However, the clinical efficacy of cisplatin in ovarian cancer is limited due to the development of chemo-resistance during treatment. OBJECTIVE: In the study, we aimed to investigate the synergistic anti-cancer activity and targets of the FDA-approved drug disulfiram combined with cisplatin in ovarian cancer. METHODS: The cell viability was determined by Celltier-Glo luminescent assay. The synergistic anti-cancer activity was assessed by combination index. Cell cycle and apoptosis were detected by flow cytometry. The in vivo anti-tumor activity and side effects were evaluated using a xenografted mice model. The synergistic anti-cancer targets were identified by a mass spectrometry-based proteomics analysis. RESULTS: In this study, we first found that disulfiram synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant ovarian cancer cells, which was accompanied by the enhanced induction of cellular apoptosis. Secondly, the in vivo study demonstrated that the combination treatment of disulfiram and cisplatin dramatically inhibited tumor growth and had no apparent side effects in ovarian cancer xenografted mice. Finally, proteomics analysis identified SMAD3 as a potential target of disulfiram-cisplatin combined treatment, and the down-regulation of SMAD3 could increase cisplatin-induced cell death in ovarian cancer. CONCLUSION: Combination treatment of disulfiram and cisplatin synergistically inhibited the growth of ovarian cancer through down-regulating SMAD3. As a repurposed drug, disulfiram could be quickly transformed into a clinic to overcome cisplatin resistance for the treatment of ovarian cancer.

Nanocarriers containing platinum compounds for combination chemotherapy.

Platinum compounds-based drugs are used widely in the clinic for the treatment of many types of cancer. However, serious undesirable side effects and intrinsic or acquired resistance limit their successful clinic use. Nanocarrier-based combination chemotherapy is considered to be an effective strategy to resolve these challenges. This review introduces the recent advance in nanocarriers containing platinum compounds for combination cancer chemotherapy, including liposomes, polymer nanoparticles, polymer micelles, mesoporous silica nanoparticles, carbon nanohors, polymer-caged nanobins, carbon nanotube, nanostructured lipid carriers, solid lipid nanoparticles, and multilayered fiber mats in detail.

Rapid Quantitative Detection of Live Escherichia coli Based on Chronoamperometry.

The rapid quantitative detection of Escherichia coli (E. coli) is of great significance for evaluating water and food safety. At present, the conventional bacteria detection methods cannot meet the requirements of rapid detection in water environments. Herein, we report a method based on chronoamperometry to rapidly and quantitatively detect live E. coli. In this study, the current indicator i0 and the electricity indicator A were used to record the cumulative effect of bacteria on an unmodified glassy carbon electrode (GCE) surface during chronoamperometric detection. Through the analysis of influencing factors and morphological characterization, it was proved that the changes of the two set electrochemical indicator signals had a good correlation with the concentration of E. coli; detection time was less than 5 min, the detection range of E. coli was 104−108 CFU/mL, and the error range was <30%. The results of parallel experiments and spiking experiments showed that this method had good repeatability, stability, and sensitivity. Humic acid and dead cells did not affect the detection results. This study not only developed a rapid quantitative detection method for E. coli in the laboratory, but also realized a bacterial detection scheme based on the theory of bacterial dissolution and adsorption for the first time, providing a new direction and theoretical basis for the development of electrochemical biosensors in the future.

Evaluation of the Toxicity of Chemical and Biogenic Insecticides to Three Outbreaking Insects in Desert Steppes of Northern China.

The locusts Oedales asiaticus (Bey-Bienko) and Myrmeleotettix palpalis (Zubovski) (Orthoptera Acrididae) and the leaf beetle Galeruca daurica (Joannis) (Coleoptera, Chrysomelidae) are economically devastating insect species in the desert steppes of Northern China. Control is mainly and frequently dependent on highly toxic chemicals. To date, there have been no complete and comprehensive reports of insecticide applications to these key pests. In this study, laboratory bioassays were carried out to determine and compare the toxicity of twelve insecticides to three outbreaking insects, O. asiaticus, M. palpalis, and G. daurica, from three typical desert steppe regions, SZWQ, XHQ and WLTQQ, respectively. The responses of the two locust species and the leaf beetle were evaluated by topical application and leaf dip bioassay techniques across a range of concentrations to develop dosage-mortality regressions. The insecticides tested included six chemical insecticides (ß-cypermethrin, imidacloprid, phoxim, λ-cyhalothrin, methomyl, chlorantraniliprole) and six biogenic insecticides (spinosad, avermectin, rotenone, matrine, azadiracthin, and methoxyfenozide). The results showed that phoxim, λ-cyhalothrin, ß-cypermethrin and spinosad showed highly toxic activity to O.asiaticus, M. palpalis, and G. daurica, while methonyl, chlorantraniliprole, and rotenone were moderately toxic to both locust species and the leaf beetle. The LC50 values of matrine, azadiractin, and avermectin were more than 1 µg a.i./adult for O. asiaticus and M. palpalis, the LC50 values of which were higher 2 g/L for G. daurica. Our findings complement information from previous similar studies and will inform future studies relating to the control of outbreaking insects, such as O.asiaticus, M. palpalis, and G. daurica in desert steppes of northern China. This study is also expected to provide basic data on the use of chemical and biogenic insecticides for application in desert steppes.

Sessilibacter corallicola gen. nov., sp. nov., a sessile bacterium isolated from coral Porites lutea.

A Gram-stain-negative, non-spore-forming, motile, aerobic bacterium (strain C21T) was isolated from coral and identified using polyphasic identification approach. Global alignment of 16S rRNA gene sequences indicated that strain C21T shares 95.7 % sequence identity to its closest neighbour, Marinibactrum halimedae NBRC 110095T, followed by other type strains with identities of lower than 95 %. The average nucleotide identity and average amino acid identity values between strain C21T and M. halimedae NBRC 110095T were 69.6 and 64.8 %, respectively, indicating that strain C21T may represent a new species in a new genus. Phylogenetic analysis based on 16S rRNA gene and phylogenomic results indicated that strain C21T forms a distinct branch in the family Cellvibrionaceae. Cellular fatty acids and polar lipids could also readily distinguish strain C21T from closely related type strains. Therefore, strain C21T is suggested to represent a new species in a new genus, for which the name Sessilibacter corallicola gen. nov., sp. nov. is proposed. The type strain is C21T (=MCCC 1K03260T=KCTC 62317T).

Repurposing Disulfiram as a Chemo-Therapeutic Sensitizer: Molecular Targets and Mechanisms.

Currently, chemotherapy is still the main strategy for cancer treatment. However, chemotherapy resistance remains a challenge. Disulfiram (DSF) is an FDA-approved medicine for the treatment of alcoholism; however, it was later revealed to have anticancer properties. Importantly, numerous studies have shown that DSF can be employed as a chemotherapeutic sensitizer to enhance the anticancer efficacy of chemo-drugs in a variety of cancers. Furthermore, the combinations of DSF and chemo-drugs have been tested in clinical trials. In the review, we summarized the possible molecular targets and mechanisms of DSF to reverse chemo-resistance. We also further discussed the opportunities and challenges of DSF as a chemo-therapeutic sensitizer. In conclusion, DSF could be a potentially repurposed drug that sensitizes cancer cells to chemotherapy in the clinic.

[BOPPPS teaching method-based effective online teaching strategies and practices for Biopharmaceutical Engineering].

Due to the COVID-19 pandemic, the teaching of Biopharmaceutical Engineering course was carried out online and completed with satisfactory outcomes. In order to improve the efficiency of online teaching, ensure the substantive equivalence between online and offline teaching and achieve effective teaching, this article summarized the exploration and practical experience of online teaching, taking the Biopharmaceutical Engineering course as an example. This includes analysis of learner characteristics, selection of online teaching platform, development of teaching resources, optimization of teaching contents, BOPPPS teaching method-based design of teaching structure, and reflection of effective teaching. This paper is expected to provide a useful reference for online teaching.

Internalization and Transport of PEGylated Lipid-Based Mixed Micelles across Caco-2 Cells Mediated by Scavenger Receptor B1.

The aim of this study was to get insight into the internalization and transport of PEGylat-ed mixed micelles loaded by vitamin K, as mediated by Scavenger Receptor B1 (SR-B1) that is abundantly expressed by intestinal epithelium cells as well as by differentiated Caco-2 cells. Inhibition of SR-B1 reduced endocytosis and transport of vitamin-K-loaded 0%, 30% and 50% PEGylated mixed micelles and decreased colocalization of the micelles with SR-B1. Confocal fluorescence microscopy, fluorescence-activated cell sorting (FACS) analysis, and surface plasmon resonance (SPR) were used to study the interaction between the mixed micelles of different compositions (varying vitamin K loading and PEG content) and SR-B1. Interaction of PEGylated micelles was independent of the vitamin K content, indicating that the PEG shell prevented vitamin K exposure at the surface of the micelles and binding with the receptor and that the PEG took over the micelles' ability to bind to the receptor. Molecular docking calculations corroborated the dual binding of both vita-min K and PEG with the binding domain of SR-B1. In conclusion, the improved colloidal stability of PEGylated mixed micelles did not compromise their cellular uptake and transport due to the affinity of PEG for SR-B1. SR-B1 is able to interact with PEGylated nanoparticles and mediates their subsequent internalization and transport.

Nickel-Catalyzed Isomerization/Allylic Cyanation of Alkenyl Alcohols.

Herein reported is a nickel-catalyzed isomerization/allylic cyanation of alkenyl alcohols, which complements current methods for the allylic substitution reactions. The specific diphosphite ligand and methanol as the solvent are crucial for the success for this transformation. A gram-scale regioconvergent experiment and formal synthesis of quebrachamine demonstrate the high potential of this methodology.

Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydrocyanation of Silyl-Substituted 1,3-Diynes.

A regiodivergent nickel-catalyzed hydrocyanation of 1-aryl-4-silyl-1,3-diynes is reported. When appropriate bisphosphine and phosphine-phosphite ligands are applied, the same starting materials can be converted into two different enynyl nitriles with good yields and high regioselectivities. The DFT calculations unveiled that the structural features of different ligands bring divergent alkyne insertion modes, which in turn lead to different regioselectivities. Moreover, the synthetic value of the cyano-containing 1,3-enynes has been demonstrated with several downstream transformations.

Controlled Pulmonary Delivery of Carrier-Free Budesonide Dry Powder by Atomic Layer Deposition.

Ideal controlled pulmonary drug delivery systems provide sustained release by retarding lung clearance mechanisms and efficient lung deposition to maintain therapeutic concentrations over prolonged time. Here, we use atomic layer deposition (ALD) to simultaneously tailor the release and aerosolization properties of inhaled drug particles without the need for lactose carrier. In particular, we deposit uniform nanoscale oxide ceramic films, such as Al2O3, TiO2, and SiO2, on micronized budesonide particles, a common active pharmaceutical ingredient for the treatment of respiratory diseases. In vitro dissolution and ex vivo isolated perfused rat lung tests demonstrate dramatically slowed release with increasing nanofilm thickness, regardless of the nature of the material. Ex situ transmission electron microscopy at various stages during dissolution unravels mostly intact nanofilms, suggesting that the release mechanism mainly involves the transport of dissolution media through the ALD films. Furthermore, in vitro aerosolization testing by fast screening impactor shows a ∼2-fold increase in fine particle fraction (FPF) for each ALD-coated budesonide formulation after 10 ALD process cycles, also applying very low patient inspiratory pressures. The higher FPFs after the ALD process are attributed to the reduction in the interparticle force arising from the ceramic surfaces, as evidenced by atomic force microscopy measurements. Finally, cell viability, cytokine release, and tissue morphology analyses verify a safe and efficacious use of ALD-coated budesonide particles at the cellular level. Therefore, surface nanoengineering by ALD is highly promising in providing the next generation of inhaled formulations with tailored characteristics of drug release and lung deposition, thereby enhancing controlled pulmonary delivery opportunities.

Surface morphology and payload synergistically caused an enhancement of the longitudinal relaxivity of a Mn3O4/PtOx nanocomposite for magnetic resonance tumor imaging.

The construction of surface structures of manganese oxide nanoparticles (MONs) in order to promote their longitudinal relaxivity r1 to surpass those of commercially available Gd(iii) complexes is still a significant challenge. Herein, we successfully obtained Mn3O4/PtOx nanocomposites (NCs) with an r1 of 20.48 mM-1 s-1, four times higher than that of commercially available Gd-DTPA (5.11 mM-1 s-1). The r2/r1 ratio of these NCs is 1.46 lower than that of Gd-DTPA (2.38). This is the first time that such excellent T1 contrast performance has been achieved using MONs via synergistically utilizing the surface morphology and surface payload. These NCs are composed of porous Mn3O4"skeleton" nanostructures decorated with tiny PtOx nanoparticles (NPs) that are realized using laser ablation and irradiation in liquid and ion etching steps. Experimental results showed that the enlarged specific area of the porous Mn3O4/PtOx NCs and the payload of ultrafine PtOx NPs synergistically facilitated the T1 contrast capabilities. The former favors sufficient proton-electron interactions and the latter reduces the global molecular tumbling motion. These NCs also exhibit an evident computed tomography (CT) attenuation value of 24.13 HU L g-1, which is much better than that achieved using the commercial product iopromide (15.9 HU L g-1). The outstanding magnetic resonance (MR) imaging and CT imaging performances of the Mn3O4/PtOx NCs were proved through in vivo experiments. Histological examinations and blood circulation assays confirmed the good biosafety of the NCs. These novel findings showcase a brand-new strategy for fabricating excellent MON T1 contrast agents (CAs) on the basis of the surface structure and they pave the way for their practical clinical applications in dual-modal imaging.

Direct access to pentenedinitriles via Ni-catalyzed dihydrocyanation of 1,3-enynes.

A highly regio- and stereoselective dihydrocyanation of 1,3-enynes was implemented by nickel/diphosphine catalysts. This reaction represents the first example of Ni-catalyzed dihydrocyanation of 1,3-enynes using TMSCN and MeOH as HCN surrogates. In this transformation, the main key feature is a multistep combination by using a single catalyst system. We observed a critical influence of the HCN source on the dihydrocyanation reaction. Moreover, the double hydrocyanation products were conveniently converted to poly-substituted pyridines.

Highly Regio- and Stereoselective Ni-Catalyzed Hydrocyanation of 1,3-Enynes.

A highly regio- and stereoselective hydrocyanation of 1,3-enynes was implemented by nickel/diphosphine catalysts. A wide range of highly regio- and stereoselective alkenyl nitriles were efficiently prepared. In this transformation, both the tethered alkene and the ligand play key roles in the reactivity and selectivity. The origin of regioselectivity was understood preliminarily by DFT studies.

Influence of PEGylation of Vitamin-K-Loaded Mixed Micelles on the Uptake by and Transport through Caco-2 Cells.

The aim of the study is to investigate the uptake by and transport through Caco-2 cells of two mixed micelle formulations (based on egg phosphatidylcholine and glycocholic acid) of vitamin K, i.e., with and without DSPE-PEG2000. The uptake of vitamin K and fluorescently labeled mixed micelles with and without PEG coating showed similar kinetics and their uptake ratio remained constant over time. Together with the fact that an inhibitor of scavenger receptor B1 (BLT-1) decreased cellular uptake of vitamin K by ∼80% compared to the uptake in the absence of this inhibitor, we conclude that both types of micelles loaded with vitamin K can be taken up intactly by Caco-2 cells via this scavenger receptor. The amount of vitamin K in chylomicrons fraction from Caco-2 cell monolayers further indicates that mixed micelles (with or without PEGylation) are likely packed into chylomicrons after internalization by Caco-2 cells. Uptake of vitamin K from PEGylated mixed micelles increased four- to five-fold at simulated gastrointestinal conditions. In conclusion, PEGylated mixed micelles are stable upon exposure to simulated gastric conditions, and as a result, they do show overall a higher cellular uptake efficiency of vitamin K as compared to mixed micelles without PEG coating.

Mixed micellar system stabilized with saponins for oral delivery of vitamin K.

Poorly soluble vitamin K cannot be absorbed by patients suffering from cholestasis due to extremely low level of bile salts in the intestine. A formulation of vitamin K including glycocholic acid (i.e. Konakion® MM), does not increase bioavailability because it is unstable due to protonation of glycocholic acid at gastric pH. To develop a stable formulation, saponins were introduced as neutral surfactants to (partly) replace glycocholic acid. Experimental design was made to investigate the effect of the composition on particle size at neutral pH and upon acidification at pH 1.5. Two formulations that were within the optimized composition window were loaded with vitamin K and those showed superior stability at low pH as compared to Konakion® MM: sizes were between 43 and 46 nm at pH 7.3 and between 46 and 58 nm after 1 h incubation at pH 1.5, respectively, but large aggregates were formed at pH 1.5 in presence of Konakion® MM. Micelles were cytocompatible with Caco-2 cells at concentration of surfactants (saponins and glycocholic acid) up to 0.15 mg/ml. Uptake of vitamin K by Caco-2 cells was 4.2-4.9 nmol/mg protein for saponins-containing formulations and 7.1 nmol/mg protein for Konakion® MM. This, together with the superior stability at low pH, makes saponins-containing mixed micelles promising oral formulations for vitamin K.

Hypoxia-induced tumor cell resistance is overcome by synergistic GAPDH-siRNA and chemotherapy co-delivered by long-circulating and cationic-interior liposomes.

Chemotherapeutic drug resistance of tumor cells under hypoxic conditions is caused by the inhibition of apoptosis by autophagy and drug efflux via adenosine triphosphate (ATP)-dependent transporter activation, among other factors. Here, we demonstrate that disrupting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression can reduce the autophagy and ATP levels in tumor cells. To test whether GAPDH knockdown is sufficient to overcome drug resistance, a nanocarrier (asymmetry-membrane liposome) was designed to encapsulate GAPDH-siRNA with a low dose of paclitaxel (PTX). Liposomes were prepared using novel cryogenic inner-outer dual reverse phase emulsion liposome manufacturing technology to obtain a high loading of siRNA. The results of dynamic light scattering (DLS) indicated that the liposomes had an average hydrodynamic diameter of 250.5 nm and polydispersity index (PDI) of 0.210, which was confirmed by (Transmission Electron Microscope) TEM images. In in vitro tests, the siRNA liposomes presented a high specificity in the suppression of GAPDH expression and significant synergy in cytotoxicity with co-delivery of PTX against tumor cells (HeLa and MCF-7) under hypoxic conditions. Moreover, in vivo studies (a HeLa tumor xenograft model using female BALB/c nude mice) demonstrate that the liposomes could not only increase the concentration of drugs in tumors over time but also successfully boosted the chemotherapeutic efficacy of PTX (synergistic therapy with GAPDH-siRNA). Tumor cells appeared to lose their resistance against PTX therapy, becoming more sensitive to PTX when GAPDH-siRNA was simultaneously administered in long-circulating liposomes. Consequently, the novel delivery of GAPDH-siRNA using nanotargeted liposomes provides a useful and potential tool to overcome multidrug resistant (MDR) tumors and presents a bright prospect compared with the traditional chemotherapeutic strategies in clinic cancer therapy.