Photothermal therapy of xenografted tumor by carbon nanoparticles-Fe(II) complex.

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). However, none of them has been applied in clinical treatment, because they have not been approved for clinical evaluations and the precise temperature control facility is scarce. In this study, we designed a temperature-responsive controller for PTT and used carbon nanoparticles-Fe(II) complex (CNSI-Fe) as photothermal conversion agent (PTA) for PTT of tumor in vitro and in vivo. CNSI-Fe was an innovative drug under the evaluations in clinical trials. CNSI-Fe showed excellent photothermal conversion ability in water to increase the water temperature by 40 °C within 5 min under irradiation of 808 nm laser at 0.5 W/cm2. The temperature was precisely controlled at 52 °C for both in vitro and in vivo tumor inhibition. CNSI-Fe with NIR irradiation showed higher tumor cell inhibition than CNSI. In tumor bearing mice, CNSI-Fe with NIR irradiation achieved an inhibition rate of 84.7 % and 71.4 % of them were completely cured. Mechanistically, CNSI-Fe under NIR irradiation induced the radical generation, oxidative damage and ferroptosis to kill tumor. In addition, CNSI-Fe showed good biosafety during PTT according to hematological, serum biological and histopathological examinations. These results indicated that the combination of chemotherapy and PTT provided higher antitumor efficiency using CNSI-Fe as PTA.

Powerful Orbital Hybridization of Copper-Silver Bimetallic Nanosheets for Electrocatalytic Nitrogen Reduction to Ammonia.

Electrochemical nitrogen reduction (eNRR) is a promising strategy to replace the energy- and capital-intensive Haber-Bosch process. Unfortunately, the low selectivity of the eNRR process impedes the industrial application of this approach. In this work, a highly efficient and stable NRR electrocatalyst is obtained via coreduction of Cu and Ag precursors using the holly leaves as reducing agents. The as-obtained Cu3Ag bimetallic nanosheets exhibit excellent NRR performance with an NH3 production rate of 31.3 µg h-1 mg-1cat. and a Faradaic efficiency of 31.3% at -0.2 V vs RHE. According to density functional theory (DFT) calculation, the outstanding performance of Cu3Ag bimetallic nanosheets could be caused by the fact that Ag optimizes the 3d orbital occupation of Cu and synergistically enhances the charge transfer during the NRR process, resulting in a suitable adsorption strength of the intermediates.

Carbon Nanoparticles-Fe(II) Complex for Efficient Tumor Inhibition with Low Toxicity by Amplifying Oxidative Stress.

The Fe element is essential for human beings, but overdose of Fe leads to unwanted toxicity. However, overwhelming Fe accumulation in tumor cells could arouse strong oxidative stress for cancer therapy. Therefore, the fast and specific accumulation of Fe in tumor cells without systemic toxicity is critical for this purpose. Herein, we report that a carbon nanoparticles-Fe(II) complex (CNSI-Fe) could efficiently load Fe into tumor cells and inhibit tumor growth with low toxicity in H22 tumor-bearing mice. Upon intratumoral injection, CNSI-Fe only induced meaningful Fe increase in the tumor to significantly inhibit tumor growth with competitive efficiency to cis-dichlorodiammineplatinum(II). Fe accumulation stimulated the hydroxyl radical generation and serious oxidative stress in the tumor. Due to the lack of Fe accumulation in other tissues, CNSI-Fe was of low systemic toxicity to tumor-bearing mice. With the clinical success of CNSI for decades, CNSI-Fe might be used for cancer therapy through "off label" use to benefit patients immediately.

Carbon nanoparticles suspension injection for photothermal therapy of xenografted human thyroid carcinoma in vivo.

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). Carbon nanoparticles suspension injection (CNSI) is a commercial imaging reagent for lymph node mapping. CNSI has similar structural characteristics to other carbon nanomaterials, and thus, might be applied as photothermal agent. Herein, we evaluated the photothermal conversion ability and therapeutic effects of CNSI on thyroid carcinoma. CNSI was composed by carbon nanoparticle cores and polyvinylpyrrolidone K30 as the dispersion reagent. CNSI absorbed NIR light efficiently following the Lambert-Beer law. The temperature of CNSI dispersion increased quickly under the NIR irradiation. CNSI killed the TCP-1 thyroid carcinoma cells under 808 nm laser irradiation at 0.5 W/cm2, while CNSI or NIR irradiation treatment alone did not demonstrate this effect. Temperature increases were observed in tumor injected with CNSI under NIR irradiation. After three irradiation treatments, the tumor growth was completely blocked and the disruption of cellular structure was observed. When the tumor temperatures reached 53°C during treatment, the tumors did not recur within the observation period of 3 months. Our results suggested that CNSI might be used for PTT through "off label" use to benefit the patients immediately.

Carbon nanoparticles suspension injection for the delivery of doxorubicin: Comparable efficacy and reduced toxicity.

Drug delivery systems for doxorubicin (DOX) have attracted tremendous interest nowadays for the improved efficacy and/or reduced toxicity. Due to the aromatic structures and hydrophobic domains, carbon nanoparticle suspension injection (CNSI), a clinical applied reagent for lymph node mapping, strongly adsorbs DOX and holds great potential in cancer therapy. Herein, we evaluated the therapeutic effects of CNSI-DOX to establish its delivery applications for cancer drugs. CNSI adsorbed DOX from solution quickly after the mixing, and the release of DOX from CNSI followed a pH-dependent way. CNSI-DOX and free DOX had nearly identical inhibitive effects on cancer cells, while the vehicle CNSI was nontoxic. CNSI-DOX largely prolonged the life span of ascites tumor bearing mice after the intraperitoneally injection and the ascites weights showed significant decreases. CNSI-DOX also inhibited the growth of subcutaneous xenografts following the same administration route. The therapeutic efficacy of CNSI-DOX was similar to that of free DOX in ascites tumor model, but slightly lower in subcutaneous xenografts model. The advantage of using CNSI was majorly reflected by the reduced toxicity of DOX according to the bodyweight changes, serum biochemical indicators and histopathological observations. The LD50 (median lethal dose) value of CNSI-DOX was 43.8 mg/kg bodyweight, nearly three times of that of free DOX (15.2 mg/kg bodyweight). Our results suggested that CNSI might be used for DOX delivery through "off label" use to benefit the patients immediately.

Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice.

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period. The body weight increases were similar among the exposed groups and the control group. The parameters of hematology and serum biochemistry remained nearly unchanged, with very few of them showing significant changes. The low toxicity of CNSI was also reflected by the unchanged histopathological characteristics of these organs. The injection of CNSI did not induce higher apoptosis levels either. The slight oxidative stress was observed in RES organs at high dosages at day 7 post-exposure. The implication to the clinical applications and toxicological evaluations of carbon nanomaterials is discussed.

Skeleton labeled 13C-carbon nanoparticles for the imaging and quantification in tumor drainage lymph nodes.

Carbon nanoparticles (CNPs) have been widely used in tumor drainage lymph node (TDLN) imaging, drug delivery, photothermal therapy, and so on. However, during the theranostic applications, the accumulation efficiency of CNPs in target organs is unknown yet, which largely hinders the extension of CNPs into clinical uses. Herein, we prepared skeleton-labeled 13C-CNPs that had identical properties to commercial CNPs suspension injection (CNSI) for the imaging and quantification in TDLN. 13C-CNPs were prepared by arc discharge method, followed by homogenization with polyvinylpyrrolidone. The size distribution and morphology of 13C-CNPs were nearly the same as those of CNSI under transmission electron microscope. The hydrodynamic radii of both 13C-CNPs and CNSI were similar, too. According to X-ray photoelectron spectroscopy and infrared spectroscopy analyses, the chemical compositions and chemical states of elements were also nearly identical for both labeled and commercial forms. The skeleton labeling of 13C was reflected by the shift of G-band toward lower frequency in Raman spectra. 13C-CNPs showed competitive performance in TDLN imaging, where the three lymph nodes (popliteal lymph node, common iliac artery lymph node, and paraaortic lymph node) were stained black upon the injection into the hind extremity of mice. The direct quantification of 13C-CNPs indicated that 877 µg/g of 13C-CNPs accumulated in the first station of TDLN (popliteal lymph node). The second station of TDLN (common iliac artery lymph node) had even higher accumulation level (1,062 µg/g), suggesting that 13C-CNPs migrated efficiently along lymphatic vessel. The value decreased to 405 µg/g in the third station of TDLN (paraaortic lymph node). Therefore, the 13C-CNPs provided quantitative approach to image and quantify CNSI in biological systems. The implication in biomedical applications and biosafety evaluations of CNSI is discussed.

[Preparation and evaluation of pharmacodynamic of the pectin-doxorubicin conjugate nanosuspensions].

This study was conducted to produce pectin-doxorubicin conjugate（PDC） nanosuspensions by high-pressure homogenization, and investigating the physico-chemical properties, the cumulative release rate in vitro and in vivo, and the anti-tumor activity. The major production parameters such as pressure, cycle numbers and types of stabilizers on the mean particle size and polydispersity index（PI） of PDC nanosuspensions were investigated. The cumulative release rate in phosphate buffer saline（PBS） at pH 5.1 or 7.0 were studied. The concentration of doxorubicin（DOX） in plasma of rabbit were recorded after intraperitoneal injection of PDC nanosuspensions(DOX was equivalent to 10 mg·kg-1) or DOX (10 mg·kg-1). We established an animal model of the nude mice with SKOV3 cell, and injected the PDC nanosuspensions(DOX was equivalent to 10, 5, 2.5 mg·kg-1) in the first day, and observed the growth state of nude mice. The particle size of PDC nanosuspensions was 118.8 ± 6.93 nm, PI was 0.14 ± 0.03, as well as the zeta potential was -27.2 ± 0.36 m V. It shows that no drug release was found in PBS at p H 7.4. About 40% cumulative release was determined in PBS at 5.1 after 30 h. The concentration of DOX in plasma of PDC group was 60 ng·mL-1, and was lower than that of DOX group. Compared with control group, high-dose-group decreased the weight of nude mice's ascites tumor and burrknot. PDC nanosuspensions can inhibit the growth of SKOV3 cell line in nude mice.In summary, PDC nanosuspensions are target-specific drugs with high efficiency and low toxicity in the ascites cancer model.

Effect of nano-hydroxyapatite suspension on cell proliferation and cycle in human periodontal ligament cells.

The study was aimed to provide insights into the effect of nano-hydroxyapatite (nHA) suspension on cell proliferation and cycle of human periodontal ligament cells, offering the evidence for nHA being used in periodontal therapy. Human periodontal ligament cells (HPDLCs) were cultured in different concentrations of nano-hydroxyapatite/sodium carboxymethyl cellulose (nHA-CMCNa) suspension in vitro. After that, cell proliferation ability was examined by MTT [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and flow cytometry. MTT assay demonstrated that the Relative Proliferation Rate (RPR) of 0.5% nHA-CMCNa group was significantly higher than other groups (p <0.05), which means that nHA-CMCNa might increase cell proliferation ability. Flow cytometry showed that cells in G1 phase decreased, whilst cells in S phase increased after cultured in nHA-CMCNa suspension for 48 h. The result suggested that part of cells finished G1 phase in advance and get into S phase earlier, which speed up the cell proliferation, nHA-CMCNa suspension had great effect on cell proliferation. The high concentration of nHA-CMCNa could shorten the time in G1 phase, impel part of cells into S phase, and accelerate proliferation rate of HPDLCs.

Preparation and characterization of poly(pluronic-co-L-lactide) nanofibers for tissue engineering.

In this work, a new kind of biodegradable poly(pluronic-co-L-lactide) (Pluronic-PLLA copolymers) was successfully prepared by melt-polycondensation method from L-lactide, Pluronic and isophorone diisocyanate (IPDI). The obtained copolymers were characterized by (1)H NMR, FT-IR, X-ray, and TGA/DTA. Meanwhile, three-dimensional (3-D) porous scaffolds based on Pluronic-PLLA were prepared by the electrospinning method, the factors of concentration, flow rate and voltage that influence the formation of the Pluronic-PLLA nanofibers were studied and the structure of Pluronic-PLLA nanofibers were investigated by scanning electron microscopy (SEM). MTT results revealed that the Pluronic-PLLA scaffolds had good biocompatibility and nontoxicity. Morphological study using fluorescence micrographs and scanning electron microscopy showed that in vitro osteoblast cell culture demonstrated the electrospun Pluronic-PLLA composite scaffolds could provide a suitable environment for good cell attachment. These results suggested that such Pluronic-PLLA nanofibers membranes might have prospective applications in tissue engineering field.

Preparation and in vitro characterization of dexamethasone-loaded poly(D,L-lactic acid) microspheres embedded in poly(ethylene glycol)-poly({varepsilon}-caprolactone)-poly(ethylene glycol) hydrogel for orthopedic tissue engineering.

The corium is decreased to about half of its thickness in skin defects and wrinkles due to gravity and environment. In this study, dexamethasone/poly(d,l-lactic acid) (Mn = 160,000) microspheres were incorporated into poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (Mn = 3300) hydrogel to prepare an injectable hydrogel composite. The composite was designed to increase the thickness of the corium. Dexamethasone/poly(d,l-lactic acid) microspheres were prepared by oil-in-water emulsion/solvent evaporation technique. The properties of microspheres were investigated by size distribution measurement, scanning electron microscope and x-ray diffraction. Drug loading, encapsulation efficiency, and drug delivery behavior of microspheres were also studied in detail. Cell adhesion of microspheres was investigated by NIH3T3 cell in vitro. The properties of hydrogel composite were investigated by scanning electron microscope, rheological measurements and methyl thiazolyl tetrazolium assay. Drug release from composite was determined by HPLC-UV analysis. These results suggested that poly(d,l-lactic acid) microspheres encapsulating dexamethasone embedded in poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) hydrogel might have prospective application in orthopedic tissue engineering field.

Biodegradable self-assembled MPEG-PCL micelles for hydrophobic oridonin delivery in vitro.

The great potential of oridonin (ORI) for clinical application in cancer therapy is greatly limited due to its poor water-solubility. The purpose of this study was to increase the water solubility of oridonin using monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) as drug carrier. The ORI-loaded MPEG-PCL micelles were prepared by thin film hydration method. The obtained ORI-micelles could be lyophilized into powder form, which could be re-dissolved in water to form homogeneous solution. This study showed that ORI was successfully incorporated in the core-shell structure of MPEG-PCL micelles and maintained its anticancer activity. The average particle size was 25.55 +/- 0.10 nm and the mean zeta potential was -4.71 +/- 0.05 mV. The actual drug loading and encapsulation efficiency were 7.99 +/- 0.03% and 99.51 +/- 0.34%, respectively. ORI could be released from MPEG-PCL micelles in a sustained manner in vitro. The permeation profiles of ORI from ORI-micelles and ORI water saturated solution through excised mouse skin demonstrated that ORI-micelles showed much better transdermal penetration performance than ORI water saturated solution. The prepared ORI-micelles have great potential for both direct intravascular administration and being further developed as a transdermal drug delivery system in cancer chemotherapy.

The chromosomal protein HMGN2 mediates the LPS-induced expression of ß-defensins in mice.

Human ß-defensin-2 (HBD-2), an antimicrobial peptide produced by epithelial cells, plays an important role in the body's innate and adaptive immunity. High-mobility group N2 (HMGN2), a member of the HMG superfamily, binds to chromatin to modulate gene transcription. Previously, we have shown that HMGN2 acts as a positive modulator of the signal transduction cascade in the process of inducible human ß-defensin expression. In our current study, we found that down-regulation of HMGN2 reduces the expression level of murine ß-defensin-3 and -4 (mBD-3 and mBD-4), but not mBD-1 upon LPS stimulation in various tissues of pregnant ICR mice, as well as in embryonic and neonatal lungs and livers at different developmental time points. In the control group, murine HMGN2 expression decreased, while mBD-1 and mBD-4 expression increased slightly during development. In the LPS-treated groups, murine HMGN2 and mBD-1 expression did not change significantly, whereas mBD-3 and mBD-4 expression significantly increased in maternal, embryonic, and neonatal tissues, especially the mBD-3 expression. HMGN2 shRNA interference led to decreased mBD-3 and mBD-4 expression, while mBD-1 expression did not significantly change. These results demonstrate that HMGN2 is a component of the LPS-induced mouse ß-defensin response.

Penetration enhancement of lidocaine hydrochlorid by a novel chitosan coated elastic liposome for transdermal drug delivery.

An effective transdermal delivery system for local anaesthetic was developed with lidocaine hydrochloride (LID) as model drug. Chitosan coated elastic liposome (CCEL) were proposed and its in vitro/in vivo skin permeation properties were evaluated. Elastic liposome composed of soya lecithin with sodium deoxycholate (SDC) as edge activator, was prepared by rotary evaporation-sonication method. Chitosan (CH) (0.1-0.5%, w/v) coated elastic liposome by electrostatic attraction of negative elastic liposome and positive CH. CH coating changed the elastic liposome surface charge and increased the vesicle size. The drug encapsulation efficiency (EE) decreased with the increase of CH content. CH coated elastic liposome demonstrated an improved physicochemical stability at 4 degrees C in a 3 months storage period. After coated, CCEL displayed a prolonged drug release profile in vitro release study. The in vitro/in vivo studies showed that CCEL were able to give a statistically significant improvement of skin permeation of LID and significantly reduced pain in comparison with elastic liposome and CH solution.

Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis patients and peri-implantitis

High mobility group chromosomal protein B1 (HMGB1) and N2 (HMGN2), two members of High mobility group (HMG) family, play important role in inflammation. The purposes of this study were to investigate the expression of HMGB1 and HMGN2 in periodontistis. The expression of HMGB1 and HMGN2 mRNA in gingival tissues and gingival crevicular fluid (GCF) in chronic periodontitis (CP), generalized aggressive periodontitis (G-AgP) patients and healthy subjects was detected by real-time PCR. The protein level of HMGB1 and HMGN2 in peri-implant crevicular fluid (PICF), peri-implant crevicular fluid of peri-implantitis (PI-PICF) and normal patients was determined by Western blotting. Furthermore, IL-1â, IL-6, IL-8, TNF-á and HMGB1 levels in GCF, PI-PICF and healthy-PICF samples from different groups were determined by ELISA. HMGN2 expression was increased in inflamed gingival tissues and GCF from CP and G-ApG groups compared to control group. HMGB1 expression was the highest in the gingival tissues and GCF from CP patients and was accompanied by increased concentrations of IL-1â, IL-6, IL-8 proinflammaory cytokines. To our knowledge, this is the first study reporting that the expression of HMGB1 and HMGN2 was increased in the gingival tissues and GCF in CP and G-AgP and the PICF in PICF. Our data suggest that HMGB1 may be a potential target for the therapy of periodontitis and PI.

Preparation and characterization of nano-hydroxyapatite/poly(vinyl alcohol) composite membranes for guided bone regeneration.

In this study, nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite membranes were prepared by solvent casting and evaporation method. The morphology, mechanical properties, water absorption behavior, contact angle measurement and biocompatibility of these membranes were examined by SEM, FTIR, XRD, MTT assay and etc. The results demonstrate that the surface of composite membranes is suitable for the adhesion and proliferation of osteogenic cells, and that n-HA and PVA are in uniform distribution when the content of n-HA is less than 20 wt%. Tests of swelling behavior and water contact angle show that the incorporation of n-HA into PVA matrix significantly reduces its hydrophilicity. Mechanical tests reveal that the addition of n-HA nanoparticles reduces tensile strength and elongation rate but increases Young's modulus of composite membranes. Cell attachment test and MTT assay prove that n-HA/PVA composite membranes have good biocompatibility. Therefore, the n-HA/PVA composite membranes possess potential application for guided bone regeneration (GBR).

Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis patients and peri-implantitis.

BACKGROUND AND OBJECTIVE: High mobility group chromosomal protein B1 (HMGB1) and N2 (HMGN2), two members of high mobility group (HMG) family, play important role in inflammation. The purpose of this study was to investigate the expression of HMGB1 and HMGN2 in periodontistis. MATERIALS AND METHODS: The expression of HMGB1 and HMGN2 mRNA in gingival tissues and gingival crevicular fluid (GCF) in chronic periodontitis (CP), generalised aggressive periodontitis (G-AgP) patients and healthy subjects was detected by real-time PCR. The protein level of HMGB1 and HMGN2 in peri-implant crevicular fluid (PICF), peri-implant crevicular fluid of peri-implantitis (PI-PICF) and normal patients was determined by Western blotting. Furthermore, IL-1ß, IL-6, IL-8, TNF-α and HMGB1 levels in GCF, PI-PICF and healthy-PICF samples from different groups were determined by ELISA. RESULTS: HMGN2 expression was increased in inflamed gingival tissues and GCF from CP and G-ApG groups compared to control group. HMGB1 expression was the highest in the gingival tissues and GCF from CP patients and was accompanied by increased concentrations of IL-1ß, IL-6, IL-8 proinflammaory cytokines. CONCLUSION: To our knowledge, this is the first study reporting that the expression of HMGB1 and HMGN2 was increased in the gingival tissues and GCF in CP and G-AgP and the PICF in PICF. Our data suggest that HMGB1 may be a potential target for the therapy of periodontitis and PI.

Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis patients and peri-implantitis.

High mobility group chromosomal protein B1 (HMGB1) and N2 (HMGN2), two members of High mobility group (HMG) family, play important role in inflammation. The purposes of this study were to investigate the expression of HMGB1 and HMGN2 in periodontistis. The expression of HMGB1 and HMGN2 mRNA in gingival tissues and gingival crevicular fluid (GCF) in chronic periodontitis (CP), generalized aggressive periodontitis (G-AgP) patients and healthy subjects was detected by real-time PCR. The protein level of HMGB1 and HMGN2 in peri-implant crevicular fluid (PICF), peri-implant crevicular fluid of peri-implantitis (PI-PICF) and normal patients was determined by Western blotting. Furthermore, IL-1ß, IL-6, IL-8, TNF-α and HMGB1 levels in GCF, PI-PICF and healthy -PICF samples from different groups were determined by ELISA. HMGN2 expression was increased in inflamed gingival tissues and GCF from CP and G-ApG groups compared to control group. HMGB1 expression was the highest in the gingival tissues and GCF from CP patients and was accompanied by increased concentrations of IL-1ß, IL-6, IL-8 proinflammaory cytokines. To our knowledge, this is the first study reporting that the expression of HMGB1 and HMGN2 was increased in the gingival tissues and GCF in CP and G-AgP and the PICF in PICF. Our data suggest that HMGB1 may be a potential target for the therapy of periodontitis and PI.

Synthesis, characterization, and in vitro and in vivo evaluation of a novel pectin-adriamycin conjugate.

Adriamycin (ADM) has been widely used in the treatment of many types of solid malignant tumor. However, cardiotoxicity, multidrug resistance and a short half-life in vivo are significant problems that limit its clinical application. To resolve these problems, a novel pectin-adriamycin conjugate (PAC) was synthesized by attaching ADM to low-methoxylated pectin via an amide linkage. The ADM content and weight-average molecular weight (Mw) of PAC were greater than 25% (w/w) and 50,360 g/mol, respectively. PAC was highly stable in plasma, but 33.2% of ADM was released from PAC after incubation for 30 h with lysosomes derived from rat liver. PAC was distributed uniformly in the cytoplasm of most A549 cells and accumulated in the nucleus of a few A549 cells after incubation for 30 h. At concentrations equivalent to 0.125-1.000 microg of ADM/mL, PAC did not inhibit the growth of either A594 or B16 cells to the same extent as free ADM or a mixture of ADM and pectin. Interestingly, at all concentrations, PAC inhibited the growth of 2780cp cells in vitro significantly more effectively than ADM or the mixture of ADM and pectin. The anticancer effect of PAC in vivo was evaluated with C57BL/6 mice bearing pulmonary metastases of B16 cells. Compared with ADM and the mixture of ADM and pectin, PAC suppressed tumor growth significantly and prolonged the mean survival time of the B16-inoculated mice. PAC has great potential for development as a tumor targeting polymer-drug.

[Preparation and lymphatic targeting research of targeting antitumor drug: pectin-adriamycin conjugates].

Pectin, a polysaccharide extracted from the cell wall of plants, was used as the drug carrier to synthesize the pectin-adriamycin conjugates (P(A)n). The structure of the conjugates was confirmed by UV and IR. The degree of esterification (DE) of the pectin was assessed, and it was found that DE significantly influenced the carboxy group contents, inherent viscosity and galacturonic acid contents of the pectin. The results of drug release test in vitro showed that the conjugate was stable in normal saline, but was gradually enzymolyzed to release the adriamycin in blood plasma and in lymph nodes. The results of lymphatic targeting study of P(A), demonstrated that the modification of DE or drug coupling capacity of pectin significantly influenced the lymphatic targeting characteristics of P (A)n. The adriamycin concentration of lymph nodes was 208 times higher than that of plasma after local injection of the P(A)n, of which the adriamycin content was 27.9% and the pectin was deesterificated 120 minutes by the use of hypothermy alkaline deesterification method.