Prevalence and unfavorable outcome of frailty in older adults with gastric cancer: a systematic review and meta-analysis.

BACKGROUND AND AIM: Previous studies reported inconsistent results on the prevalence and prognostic implications of frailty among older adults with gastric cancer. This systematic review synthesized available literature pertaining on this topic to establish the prevalence and unfavorable outcomes of frailty in older adults with gastric cancer. METHODS: A comprehensive search was conducted across multiple English databases including PubMed, Cochrane Library, CINAHL, Embase, and Web of Science as well as Chinese databases, namely, CNKI, Wan Fang, and CBM, from inception to July 4, 2023, to identify potential studies. Data related to the incidence of frailty and its unfavorable outcomes in older adults with gastric cancer were extracted. RevMan5.3 and R 4.2.2 were used to evaluate pooled prevalence, hazard ratios (HR), and 95% confidence interval (CI). RESULTS: This review comprehensively selected 13 studies, comprising 9 cohort studies and 4 cross-sectional studies, on 44,117 older adults diagnosed with gastric cancer. The incidence of frailty among older adults with gastric cancer ranged from 10 to 71%. The pooled prevalence of frailty was 29% (95% CI 0.21-0.39). Frailty was found to be associated with an elevated risk of postoperative complications (HR = 1.99, 95% CI 1.45-2.73), prolonged postoperative hospital stay (HR = 2.68, 95% CI 2.38-3.02), likelihood of readmission (HR = 3.28, 95% CI 1.77-6.08), and an increased mortality risk (HR = 1.60, 95% CI 1.36-1.90). CONCLUSIONS: Frailty was associated with a poor prognosis in older adults with gastric cancer. Clinical medical staff should focus on the frailty of older adults with gastric cancer, conduct large-scale, multicenter, and prospective studies and early screening of patients, and provide guidance for the implementation of prevention and treatment strategies.

Relation between frailty and adverse outcomes in elderly patients with gastric cancer: a scoping review.

Background: Playing an exemplary role, frailty have crucial effect on the preoperative evaluation of elderly patients. Previous studies have shown that frailty is associated with complications and mortality in patients with gastric cancer (GC). However, with the development of the concept of "patient-centered", the range of health-related outcomes is broad. The differences in relation between frailty and various adverse outcomes will be further explored. Method: The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases were searched for keywords, including frailty (such as frail) and gastric cancer (such as stomach neoplasms or stomach cancer or gastrectomy or gastric surgery). The search period is until August 2023. The included studies were observational or cohort studies with postoperative related adverse outcomes as primary or secondary outcome measures. Valid assessment tools were used. The Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess methodological quality in the included literature. Result: Fifteen studies were included, including 4 cross-sectional studies, 8 retrospective cohort studies, and 3 prospective cohort studies. Among them, 6 studies were rated as "Good" and 9 studies were rated as "Fair," indicating that the quality of the literature was high. Then, 10 frailty assessment tools were summarized and classified into two broad categories in accordance with frailty models. Results of the included studies indicated that frailty in elderly patients with GC was associated with postoperative complications, mortality, hospital days, readmissions, quality of life, non-home discharge, and admission to the intensive care unit. Conclusion: This scoping review concludes that high levels of preoperative frailty increase the risk of adverse outcomes in elderly patients with GC. Frailty will be widely used in the future clinical evaluation of elderly gastric cancer patients, precise risk stratification should be implemented for patients, and frailty management should be implemented well to reduce the occurrence of adverse treatment outcomes.

The clip-segment of the von Willebrand domain 1 of the BMP modulator protein Crossveinless 2 is preformed.

Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop.

Application of liposome encapsulation technique to improve anti-carcinoma effect of resveratrol.

AIM: The promising anti-tumor effect of resveratrol (RES) has aroused much interest in recent years, but its clinical application was seriously hindered due to its poor solubility in water. The aim of this study was to improve the water solubility of RES by liposome encapsulation technique for effective tumor treatment. METHODS: This study develops two liposomal formulations to solubilize RES by reverse-phase evaporation method with or without poly(ethylene glycol-2000)-grafted distearolyl phosphatidylethanolamine (DSPE-PEG(2000)). The effect of different formulation factors on the encapsulation efficiency (EE) and the particle sizes were investigated. These factors included the mass ratio of drug to soybean phosphatidylcholine (drug/SPC), the mass ratio of cholesterol to soybean phosphatidylcholine (chol/SPC), the volume ratio of water phase/organic phase and the microfluidization process. The drug release studies were performed in various media, simulating the desired application conditions. The cytotoxicity study was carried out by MTT assay on HeLa and Hep G2 cell lines. RESULTS: The RES EE of 95% was obtained when using drug/SPC (1:40 mass ratio), Chol/SPC (1:10 mass ratio), water phase/oil phase (1:2 volume ratio), microfluidization process (entrance pressure 6 kpa, two times of cycle time). The addition of DSPE-PEG(2000) into the formulation showed little effect on the formation and properties of RES liposome. The release of RES was pH-independent. RES liposomes and PEG-modified liposomes performed significant inhibition effects on both cells growth due to the solubilized RES. CONCLUSION: RES can be effectively loaded into liposomes and its anti-cancer effect was evidently improved by the application of liposome encapsulation technique.

Anti-hepatitis B virus X protein in sera is one of the markers of development of liver cirrhosis and liver cancer mediated by HBV.

Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the significance of circulating antibody to hepatitis B virus X antigen (anti-HBx) in sera remains unclear. In the present study, we examined the titers of anti-HBx (IgG) in the sera from 173 patients with chronic hepatitis B (CHB), 106 liver cirrhosis (LC), and 61 HCC by enzyme-linked immunosorbent assay (ELISA), respectively. Our data showed that the positive rates of anti-HBx were higher in sera of LC (40.6%) and HCC (34.4%) than those of CHB (10.4%), P < .05. In all 40 patients with anti-HBx+ out of 340 patients, 39 (97.5%) were HBsAg/HBeAg/anti-HBc+ and 1 (2.5%) was anti-HBs+ (P < .01), suggesting that anti-HBx in sera is a marker of HBV replication rather than a protective antibody. Thus, our findings reveal that circulating anti-HBx in sera is one of the markers of development of LC and HCC mediated by HBV.

Polymeric nanoparticles of cholesterol-modified glycol chitosan for doxorubicin delivery: preparation and in-vitro and in-vivo characterization.

OBJECTIVES: Polymeric nanoparticles have been extensively studied as drug carriers. Chitosan and its derivatives have attracted significant attention in this regard but have limited application because of insolubility in biological solution. In this work, we attempted to utilize cholesterol-modified glycol chitosan (CHGC) self-aggregated nanoparticles to increase aqueous solubility, and to reduce side effects and enhance the antitumour efficacy of the anticancer drug doxorubicin. Methods CHGC nanoparticles were loaded with doxorubicin by a dialysis method, and their characteristics were determined by transmission electron microscopy examination, light-scattering study, in-vitro drug-release study, pharmacokinetic study in rats and in-vivo antitumour activity in mice. KEY FINDINGS: The resulting doxorubicin-loaded CHGC nanoparticles (DCNs) formed self-assembled aggregates in aqueous medium. From the observation by transmission electron microscopy, DCNs were almost spherical in shape. The mean diameters of these nanoparticles determined by dynamic light scattering were in the range of 237-336 nm as the doxorubicin-loading content increased from 1.73% to 9.36%. In-vitro data indicated that doxorubicin release from DCNs was much faster in phosphate-buffered saline at pH 5.5 than at pH 6.5 and 7.4, and the release rate was dependent on the loading content of doxorubicin in these nanoparticles. It was observed that DCN-16 (drug loaded content: 9.36%) exhibited prolonged circulation time in rat plasma and showed higher antitumour efficacy against S180-bearing mice than free doxorubicin. CONCLUSIONS: These results indicated that CHGC nanoparticles had potential as a carrier for insoluble anticancer drugs in cancer therapy.

Crystallization and preliminary X-ray analysis of the complex of the first von Willebrand type C domain bound to bone morphogenetic protein 2.

Crossveinless 2 (CV2) is a member of the chordin family, a protein superfamily that modulates the activity of bone morphogenetic proteins such as BMP2. The BMPs represent a large group of secreted proteins that control many steps during embryonal development and in tissue and organ homeostasis in the adult organism. The gene encoding the first von Willebrand type C domain (VWC1) of CV2 was cloned, expressed in Escherichia coli and purified to homogeneity. The binary complex of CV2 VWC1 and BMP2 was purified and subjected to crystallization. Crystals of SeMet-labelled proteins were obtained in two different forms belonging to the tetragonal space groups P4(1)2(1)2 and I4(1), with unit-cell parameters a = b = 86.7, c = 139.2 A and a = b = 83.7, c = 139.6 A, respectively. Initial analysis suggests that a complete binary complex consisting of one BMP2 dimer bound to two CV2 VWC1 domains is present in the asymmetric unit.

Identification of a natural mutant of HBV X protein truncated 27 amino acids at the COOH terminal and its effect on liver cell proliferation.

AIM: To identify mutants of the hepatitis B virus (HBV) X (HBx) gene and investigate the effect of the natural mutant on liver cell proliferation. METHODS: We identified natural mutants of the HBx gene from 188 sera and 48 tissues of Chinese patients infected with HBV by PCR, respectively. Based on the identification of the mutants of HBx gene, we cloned the fragments of the mutants into the pcDNA3 vector. The biological activities of the mutants were investigated. RESULTS: We identified a natural mutant of the HBx gene with deletion from 382 to 401 base pairs from 3 sera out of 188 patients, which resulted in the expression deletion of the HBx protein from the 128th amino acid at the COOH terminal. The similar mutant with deletion from 382 base pair at the COOH terminal was identified from 5 cases of genomes out of 48 hepatocellular carcinoma tissues. Regarding the biological activities of the mutant, we found that the mutant of the HBx protein failed to induce apoptosis by transient transfection, but promoted proliferation of human liver immortalized L-O2 cells by stable transfection, compared with the wild-type HBx protein. The data showed that the proliferation of the mutant stably-transfected L-O2-X-Sera cells and fragment stably-transfected L-O2-XDelta127 cells was enhanced by the BrdU incorporation assay and flow cytometry analysis. Luciferase reporter gene assay showed that the transcriptional activities of NF-kappaB, survivin, and human telomerase reverse transcriptase were upregulated, and Western blot analysis revealed that the expression levels of c-Myc and proliferating cell nuclear antigen (PCNA) were upregulated in the cells. CONCLUSION: Our findings suggest that the natural HBx mutant truncated 27 amino acids at the COOH terminal promotes cell proliferation.

Self-assembled polyethylenimine-graft-poly(epsilon-caprolactone) micelles as potential dual carriers of genes and anticancer drugs.

A series of amphiphilic cationic graft polymers (PEC) were synthesized by coupling poly(epsilon-caprolactone) of differing molecular weights (MW) to low MW branched polyethylenimine via an amide group. IR, (1)H-NMR and GPC were employed to characterize the graft copolymers. The self-assembly characteristics of these copolymers in an aqueous solution were studied by fluorescence techniques. The critical micelle concentration (CMC) varied from 0.044 to 0.032g/L when the MW of poly(epsilon-caprolactone) increased from 1,800 to 5,500. The micelles formed electrostatic complexes with a reporter gene (pCMV-Luc) after an anticancer drug, Doxorubicin (DOX), was loaded by dialysis method. Gel retardation studies proved that micelles with or without DOX were able to complex with DNA completely at an equivalent N/P ratio of around 2.0, indicating that drug loading did not interfere in the interaction between the PEI shell and DNA. Particle size slightly decreased at higher N/P ratios of polyplexes, but increased with drug encapsulation. It was also noted that DNA/micelle complexes were significantly less toxic to HepG2 cells than blank PEC micelles, and improved gene transfection efficiency (about 3 orders of magnitude greater than PEI 25K alone at most) whether DOX was present in the system or not. These results suggest that this group of cationic graft polymers may be a potential candidate for the development of a drug delivery system that can examine the synergistic effects of combined drug and gene therapy.

Enhanced immune responses induced by vaccine using Sendai virosomes as carrier.

Sendai virosomes can deliver encapsulated contents into the cytoplasm directly in a virus fusion-dependent manner. In this paper, Sendai virosomes-formulated melanoma vaccine was constructed and its anti-tumor effects were investigated. The melanoma vaccine was prepared by encapsulating mixture antigen into the Sendai virosomes. The antigen, mixture proteins were extracted from B(16) melanoma cells. The cytotoxic T lymphocyte (CTL) response level was evaluated by (51)Cr release method, and the change of CD4(+) and CD8(+) expression as well as the concentration of IgG in serum of immunized mice was measured. The results showed that Sendai virosomes-formulated melanoma vaccine can effectively elicit not only systemic immune response but also strong CTL response. Sendai virosomes can be used as an effective vector for use in anti-tumor vaccine therapy.

[The role of nitric oxide in ethylene-induced stomatal closure in Vicia faba L].

The effects of nitric oxide (NO) and ethylene on Vicia faba L. stomatal movement were studied. The results showed that NO donor SNP (sodium nitroprusside) 10 micromol/L and ethylene 0.04% could induce stomatal closure distinctly and they could promote stomatal closure when treated together. When treated with AVG (an inhibitor of ethylene synthesis), c-PTIO (a specific scavenger of NO) and NaN(3) (an inhibitor of NR), the effects of NO- and ethylene-induced stomatal closure were inhibited but the inhibitor of nitric oxide synthase (NOS) had little effect. We presumed that there was coordinative effect between NO and ethylene in regulation of stomatal closure; ethylene could induce stomatal closure by regulating the production of nitrate reductase (NR)-dependent NO.

Na,K-ATPase mutations in familial hemiplegic migraine lead to functional inactivation.

The Na,K-ATPase is an ion-translocating transmembrane protein that actively maintains the electrochemical gradients for Na+ and K+ across the plasma membrane. The functional protein is a heterodimer comprising a catalytic alpha-subunit (four isoforms) and an ancillary beta-subunit (three isoforms). Mutations in the alpha2-subunit have recently been implicated in familial hemiplegic migraine type 2, but almost no thorough studies of the functional consequences of these mutations have been provided. We investigated the functional properties of the mutations L764P and W887R in the human Na,K-ATPase alpha2-subunit upon heterologous expression in Xenopus oocytes. No Na,K-ATPase-specific pump currents could be detected in cells expressing these mutants. The binding of radiolabelled [3H]ouabain to intact cells suggested that this could be due to a lack of plasma membrane expression. However, plasma membrane isolation showed that the mutated pumps are well expressed at the plasma membrane. 86Rb+-flux and ATPase activity measurements demonstrated that the mutants are inactive. Therefore, the primary disease-causing mechanism is loss-of-function of the Na,K-ATPase alpha2-isoform.

Indomethacin-loaded polymeric nanocarriers based on amphiphilic polyphosphazenes with poly (N-isopropylacrylamide) and ethyl tryptophan as side groups: Preparation, in vitro and in vivo evaluation.

The effects of copolymer composition, drug structure and initial drug feed on drug loading of polymeric micelles based on amphiphilic polyphosphazenes were investigated. It was found that the drug loading capacity of micelles based on this type of amphiphilic copolymers was mainly determined by copolymer composition and the chemical structure of drug. In addition to the compatibility between drug and micellar core, hydrogen bonding interaction between drug and hydrophilic corona may significantly influence drug loading as well. In vitro drug release in 0.1 M PBS (pH 7.4) suggested that indomethacin (IND) in the micelles was released through Fickian diffusion, and no significant difference in release rate was observed for micelles based on copolymers with various EtTrp content. Compared with in vitro IND release profile, in vivo pharmacokinetic study after subcutaneous administration provides a more sustained release behavior. Additionally, in comparison with free drug solution at the same dose, IND concentration in rat plasma showed a prolonged retention when the drug was delivered through polymeric micelles. In vivo pharmacodynamic study based on both carrageenan-induced acute and complete Freund's adjuvant-induced adjuvant arthritis model indicated that sustained therapeutic efficacy could be achieved through intraarticular injection of IND-loaded micelles. Most importantly, local delivery of IND can avoid the severe gastrointestinal stimulation, which was frequently associated with oral administration.

Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study.

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.

Cocultivation of umbilical cord blood CD34+ cells with retro-transduced hMSCs leads to effective amplification of long-term culture-initiating cells.

AIM: To establish a novel coculture system for ex vivo expansion of umbilical cord blood(UCB) hematopoietic progenitors using thrombopoietin (TPO)/Flt-3 ligand (FL)-transduced human marrow-derived mesenchymal stem cells (tfhMSCs) as feeder. METHODS: UCB CD34+ cells were isolated and cultured using four culture systems in serum-containing or serum-free medium. Suitable aliquots of cultured cells were used to monitor cell production, clonogenic activity, and long-term culture-initiating culture (LTC-IC) output. Finally, the severe-combined immunodeficient (SCID) mouse-repopulating cell (SRC) assay was performed to confirm ability of the cultured cells to reconstitute long-term hematopoiesis. RESULTS: There were no significant differences in the number of total nucleated cells among different culture systems in serum-containing medium during 21-d culture. However, on d 14, the outputs of CD34+ cells, CFU-C and CFU-GEMM in tfhMSCs coculture system were significantly enhanced. LTC-IC assay demonstrated that the tfhMSCs coculture system had the most powerful activity. The severe-combined immunodeficient (SCID) mouse repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. Furthermore, PCR analysis demonstrated the presence of human hematopoietic cells in the bone marrow and peripheral blood cells of NOD/SCID mice. CONCLUSION: The TPO/FL-transduced hMSCs, in combination with additive cytokines, can effectively expand hematopoietic progenitors from UCB in vitro and the tfhMSCs coculture system may be a suitable system for ex vivo manipulation of primitive progenitor cells under contact culture conditions.

Thymosin-loaded enteric microspheres for oral administration: preparation and in vitro release studies.

Thymosin, a water-soluble polypeptide compound, was encapsulated within enteric microspheres of acrylic acid resin II by modified oil in oil (o/o) emulsion solvent evaporation method. The mixture emulsifier composed of lecithin and Span 80 was critical to the formation of sphere-shaped thymosin microparticles. Optimizing process parameters, such as the volume ratio of organic solvent to water, initial drug feed and polymer concentration, resulted in high drug encapsulation efficiency of 89.7% (6% polymer concentration and 0.5% initial drug feed). In vitro release studies suggested that thymosin release from microspheres exhibited pH dependent profiles. For formulation with 6% polymer concentration and 0.5% initial drug feed, 68.7% thymosin was released within 4h in pH 6.8 PBS buffer, while only 6.5% was observed in acid medium.

Physicochemical characterization of polymeric micelles constructed from novel amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl 4-aminobenzoate as side groups.

An amphiphilic graft polyphosphazene (PNIPAm/EAB-PPP) composed of oligo-poly(N-isopropylacrylamide) (PNIPAm) as hydrophilic segments and ethyl 4-aminobenzoate (EAB) as hydrophobic groups was synthesized via ring-opening polymerization and subsequent substitution reaction. The molar ratio of the PNIPAm segment to EAB group was 1.85:0.15. The lower critical solution temperature (LCST) of copolymer was 32.6 degrees C as determined by turbidity method. Micellization behavior of PNIPAm/EAB-PPP in an aqueous phase was characterized by fluorescence technique, 1H NMR, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The critical micelle concentration (CMC) of the graft copolymer in aqueous solution was 0.1mg/ml. The number-averaged particle size of spherical micelles was 80 nm at 25 degrees C with a narrow distribution. TEM also revealed that inter-micellar aggregation was induced in the micelle solution at temperature above LCST of graft copolymer. The thermosensitive PNIPAm/EAB-PPP micelles may be of help to regulate the loading and release of hydrophobic drugs.

[Preparation and characterization of indomethacin/poly(N-isopropylacrylamide)-beta-cyclodextrin complex with temperature-sensitivity].

AIM: To synthesize poly(N-isopropylacrylamide)/cyclodextrin conjugate (PNIPA-beta-CD) as thermosensitive drug carrier, incorporate indomethacin into the conjugate and evaluate the drug release from the carrier in vitro. METHODS: PNIPA-beta-CD was synthesized by introducing carboxyl terminated PNIPA into the primary hydroxy group of beta-CD. The obtained conjugate was characterized by FTIR, 1H NMR and DSC. The indomethacin/PNIPA-beta-CD complex was prepared by lyophilization. In vitro drug release from the complex was carried out at 25 degrees C and 37 degrees C respectively. RESULTS: Thermosensitive PNIPA-beta-CD was synthesized successfully. The LCST is 35 degrees C, as measured by turbidity method. The drug release from indomethacin/PNIPA-beta-CD complex was slower at 37 degrees C than that at 25 degrees C. CONCLUSION: Thermosensitive PNIPA-beta-CD with molecular inclusion capacity is a potential carrier for drug sustained release.

An overview of the pharmacokinetics of polymer-based nanoassemblies and nanoparticles.

Advancements in the design and synthesis of polymer-based nanoassemblies and nanoparticles, combined with achievements in nanotechnology and medicine, have resulted in remarkable applications of polymer nanosystems in the areas of nanomedicine and pharmaceutical sciences. However, a complete understanding of the absorption, distribution, metabolism, and elimination (ADME) processes of such polymer nanosystems in living systems has not been achieved. The influences of the pharmacokinetic parameters of polymer nanomaterials on the ADME processes are reviewed in this article, with discussions of the absorption and transportation of polymer nanoparticles across biological barriers, the factors affecting the bodily distribution of polymer nanocarriers, the transformation of polymer nanomaterials in vivo, the elimination pathway of polymer nanoparticles from biological systems, and perspectives of future pharmacokinetics and safety investigations of polymer-based nanoassemblies. A full and better understanding of the pharmacokinetic parameters of polymer-based nanomaterials is of vital importance in developing polymer nanosystems with optimal pharmacokinetics and biological safety for applications in nanomedicine and the pharmaceutical industry.

Folate-modified poly(2-ethyl-2-oxazoline) as hydrophilic corona in polymeric micelles for enhanced intracellular doxorubicin delivery.

The transmembrane transport of drug loaded micelles to intracellular compartment is quite crucial for efficient drug delivery. In the current study, we investigated the cellular internalization and anticancer activity of doxorubicin loaded micelles with folate modified stealthy PEOz corona. Folate-decorated micelles incorporating doxorubicin were characterized for particle size, degree of folate decoration, drug loading content and encapsulation efficiency, morphology, and surface charge. The targeting capability and cell viability were assessed using HeLa, KB, A549 and MCF-7/ADR cell lines. In vitro study clearly illustrated the folate receptor (FR) mediated targeting of FA modified micelles to FR-positive human HeLa, KB and MCF-7/ADR cells, while specific delivery to FR-negative A549 cells was not apparently increased at the same experimental conditions. Cytotoxicity assay showed 60% and 58% decrease in IC50 values for HeLa and KB cells, while only a slight decrease for A549 cells, following treatment with folate modified formulations. The enhanced intracellular delivery of FA modified micelles in MCF-7/ADR cells was also observed. In vivo antitumor tests revealed DOX entrapped FA-PEOz-PCL micelles effectively inhibited the tumor growth and reduced the toxicity to mice compared with free DOX. The current study showed that the targeted nano-vector improved cytotoxicity of DOX and suggested that this novel PEOz endowed stealthy micelle system held great promise in tumor targeted therapy.