[Preparation and Characterization of Netupitant-loaded mPEG-PDLLA Nanoparticles].

OBJECTIVE: Methoxy poly (ethylene glycol)-poly (lactic acid) (mPEG-PDLLA) was used to increase water solubility of netupitant, thus to provide the experimental basis for development of the injection of netupitant. METHODS: Film hydration method was ultilized to prepare the netupitant-loaded mPEG-PDLLA nanoparticles (NT/mPEG-PDLLA-NPs). The preparation formulation and technology were optimized based on the single factor tests by investigating the effect of netupitant/mPEG-PDLLA mass ratio (m/m), filming temperature and time on the mean particle diameters and loading capacities. The size distributions and Zeta potentials of NT/mPEG-PDLLA-NPs were investigated using dynamic light scattering analysis, and the morphology was observed under the transmission electron microscope (TEM). The cytotoxicity of NT/mPEG-PDLLA-NPs evaluated by MTT method. RESULTS: The optimal NT/mPEG-PDLLA-NPs were achieved at the netupitant/mPEG-PDLLA mass ratio of 1/6 with filming temperature at 55 ℃ and filming time for 30 min. The resulting NT/mPEG-PDLLA-NPs displayed an opalescent and translucent appearance, with a high loading capacity of 14% and netupitant concentration of 10 mg/mL. NT/mPEG-PDLLA-NPs showed a spherical morphology, with a mean diameter of 58 nm and a nearly neutral Zeta potential of -0.29 mV. The NT/mPEG-PDLLA-NPs showed a cytotoxicity similar to free NT. CONCLUSION: Netupitant was successfully loaded into mPEG-PDLLA-NPs to significantly increased the water solubility, thus providing the experimental foundation for the further development of injection of netupitant.

Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

Efficient Inhibition of Ovarian Cancer by Gelonin Toxin Gene Delivered by Biodegradable Cationic Heparin-polyethyleneimine Nanogels.

The use of toxins for cancer therapy has great promise. Gelonin, a potent plant toxin, causes cell death by inactivating the 60S ribosomal subunit. Recently, we developed a novel gene delivery system using biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels. In the current study, the antitumor activity of a recombinant plasmid expressing gelonin (pGelonin) on human ovarian cancer was assessed. The application of HPEI nanogels, was also evaluated. Gelonin-cDNA was cloned into the pVAX1 plasmid vector and transfected into SKOV3 human ovarian cancer cells using biodegradable cationic HPEI nanogels. The expression of gelonin in vitro and in vivo was confirmed using RT-PCR and western blot analysis. Cell viability and apoptosis were examined using an MTT assay and flow cytometric analysis. For the in vivo study, an SKOV3 intraperitoneal ovarian carcinomatosis model was established, and nude mice were randomly assigned into four groups receiving i.p. administration of pGelonin/HPEI complexes, pVAX/HPEI complexes, HPEI alone and 5% glucose solution. The tumor weight was monitored, and a TUNEL assay and Ki-67 immunohistochemistry were performed to evaluate apoptosis and cell proliferation in the tumor tissue sections, respectively. Gelonin was efficiently expressed in SKOV3 cancer cells in vitro and in vivo using pGelonin incorporated with HPEI nanogels. The pGelonin/HPEI complexes inhibited cell viability and induced apoptosis in the cell culture. Treatment for intraperitoneal carcinomatosis with pGelonin/HPEI complexes reduced the tumor weight by ~58.55% compared to the control groups (P<0.05). The antitumor effect was accompanied by increased apoptosis and reduced cell proliferation (P<0.05). No significant side effects were observed with i.p. administration of the pGelonin/HPEI complexes. Our data indicate that HPEI nanogel-delivered pGelonin may have promising applications against human ovarian cancer.

NIR-II-Absorbing NDI Polymer with Superior Penetration Depth for Enhanced Photothermal Therapy Efficiency of Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary. Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice. Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects. Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.

Biomimetic Peridontium Patches for Functional Periodontal Regeneration.

The unique structure of the periodontium, including the alveolar bone, cementum, and periodontal ligament (PDL), presents difficulties for the regeneration of its intricate organization. Irreversible structural breakdown of the periodontium increases the risk of tooth loosening and loss. Although the current therapies can restore the periodontal hard tissues to a certain extent, the PDL with its high directionality of multiple groups with different orientations and functions cannot be reconstructed. Here, biomimetic peridontium patches (BPPs) for functional periodontal regeneration using a microscale continuous digital light projection bioprinting method is reported. Orthotopic transplantation in the mandibles shows effective periodontal reconstruction. The resulting bioengineered tissues closely resembles natural periodontium in terms of the "sandwich structures," especially the correctly oriented fibers, showing different and specific orientation in different regions of the tooth root, which has never been found in previous studies. Furthermore, after the assessment of clinically functional properties it is found that the regenerative periodontium can achieve stable tooth movement under orthodontic migration force with no adverse consequences. Overall, the BPPs promote reconstruction of the functional periodontium and the complex microstructure of the periodontal tissue, providing a proof of principle for the clinical functional treatment of periodontal defects.

Antitumoral efficacy by systemic delivery of heparin conjugated polyethylenimine-plasmid interleukin-15 complexes in murine models of lung metastasis.

Gene therapy shows promising application in cancer therapy, but the lack of an ideal gene delivery system is still a tough challenge for cancer gene therapy. Previously, we prepared a novel cationic nanogel, heparin-polyethylenimine (HPEI), which had potential application in gene delivery. In the present study, we constructed a plasmid with high expression efficiency of interleukin-15 (IL15) and investigated the effects HPEI-plasmid IL15 (HPEI-pIL15) complexes on the distribution level of the lung. We then evaluated the anticancer effect of HPEI-pIL15 complexes on lung metastases of B16-F10 melanoma and CT26 colon carcinoma. These results demonstrated that intravenous injection of the HPEI-pIL15 complex exhibited the highest plasmid distribution level in the lung compared with that of PEI2K-pIL15 and PEI25K-pIL15, and mice treated with HPEI-pIL15 had a lower tumor metastasis index compared with other treatment groups. Moreover, the number of natural killer cells, which were intermingled among the tumor cells, and the level of tumor necrosis factor-α and interferon-γ in the serum also increased in the pIL15-treated mice. Furthermore, the cytotoxic activity of spleen cells also increased significantly in the HPEI-pIL15 group. In addition, induction of apoptosis and inhibition of cell proliferation in lung tumor foci in the HPEI-pIL15 group was observed. Taken together, treating lung metastasis cancer with the HPEI nanogels delivered by plasmid IL15 might be a new and interesting cancer gene therapy protocol.

Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles.

In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

Preparation of core cross-linked PCL-PEG-PCL micelles for doxorubicin delivery in vitro.

Doxorubicin has been widely used in cancer treatment, but its severe side-effects restrict its clinical application greatly. So, we hope to design a novel delivery system to decrease its side-effects. In this paper, we prepared core cross-linked micelle based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (CCPCEC) at about 30 nm in diameter with a narrow distribution. The prepared core cross-linked PCL-PEG-PCL micelles were employed to load doxorubicin by pH-induced self-assembly method. Doxorubicin-loading did not obviously affect the micelle size or size distribution. Furthermore, these micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents and showed CMC in the range of 1 x 10(-3) to 2 x 10(-3) mg/mL. Cytotoxicity study confirmed great biocompatibility of the micelles and showed that the encapsulated doxorubicin in CCPCEC micelles enhanced the cytotoxicity of doxorubicin on C26 cell line in vitro. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free doxorubicin and much slower and sustained release of doxorubicin-loaded core cross-linked micelles. In addition, a faster DOX-release from micelles at pH 5.5 than that at pH 7.4 was also observed. These results suggested that this new biodegradable Core Cross-linked PCL-PEG-PCL Micelles might be potential carriers for drug delivery in cancer chemotherapy.

Fast Customization of Microneedle Arrays by Static Optical Projection Lithography.

Customized microneedle arrays (CMNAs) hold great promise for precise transdermal delivery in a minimally invasive manner. Currently, the fast customization of microneedle arrays remains a great challenge. Here, we show a static optical projection lithography (SOPL) technology for fast 3D printing CMNAs. In this technology, the digital light is statically projected to induce the spatial polymerization of monomer solutions, and therefore microneedle formation can be precisely controlled by the intensity distribution of the projected light. The obtained CMNAs do not have the stair-like surface and layer-by-layer structure that are associated with the common 3D-printing technologies. This method enables fast fabrication of CMNAs with designed shape, size, and distribution in seconds without mechanical motion system. Up-conversion nanoparticles (UCNPs) were delivered into skin by the CMNAs, to form a personalized dot matrix for in vivo information storage. Under the irradiation of near-infrared (NIR) light, the UCNPs in skin displayed a visible dot matrix, presenting information encoded in the structure of CMNAs. This work demonstrates a SOPL technology for rapidly customizing high-quality microneedle arrays and a CMNA-mediated in vivo information storage strategy.

Acute toxicity and genotoxicity studies on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanomaterials.

In the present study, we prepared poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanomaterials by solvent-extraction method. The obtained PCEC nanomaterials were studied extensively for acute toxicity and genotoxicity using bacterial reverse mutation test (Ames test), chromosomal aberration test and mouse micronucleus test. All of the Sprague-Dawley rats did not show any mortality and clinical signs of toxicity after intravenous injection at the level of 2.4g/kg body weight. Thus, the LD(50) of PCEC nanomaterials was determined to be greater than 2.4g/kg. In Ames test, PCEC nanomaterials were negative in Salmonellatyphimurium strains TA97, TA98, TA100, TA102, and TA1535 with or without metabolic activation. PCEC nanomaterials did not induce chromosomal aberrations in cultured Chinese hamster lung cells up to 5000mug/mL with or without metabolic activation. Micronucleus assay demonstrated that PCEC nanomaterials did not significantly increase micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of ICR mice or suppress bone marrow, indicating they did not cause chromosome aberrations. In conclusion, our results indicated that PCEC nanomaterials did not cause any acute toxicity and genotoxicity in our experimental conditions. Its potential to be a candidate of drug carrier is worth being further investigated.

Co-delivery honokiol and doxorubicin in MPEG-PLA nanoparticles.

The combination chemotherapy is an important protocol in cancer therapy. Honokiol shows synergistic anticancer effect with doxorubicin. In this paper, honokiol and doxorubicin co-loaded MPEG-PLA nanoparticles were prepared. The particle size, morphology, in vitro release profile, cytotoxicity and cell proliferation study were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PLA nanoparticles simultaneously, and could be released out in an extended period in vitro. Meanwhile, honokiol and doxorubicin in MPEG-PLA nanoparticle could efficiently suppress cancer cell proliferation in vitro. The described honokiol and doxorubicin co-loaded MPEG-PLA nanoparticle might be a novel anticancer agent.

3D-engineered GelMA conduit filled with ECM promotes regeneration of peripheral nerve.

Autologous transplantation remains the golden standard for peripheral nerve repair. However, many drawbacks, such as the risk of reoperation or nerve injury remain associated with this method. To date, commercially available artificial nerve conduits comprise hollow tubes. By providing physical guiding and biological cues, tissue engineered conduits are promising for bridging peripheral nerve defects. The present study focuses on the preparation of artificial composite nerve conduits by 3D bio-printing. 3D-printed molds with a tubular cavity were filled with an Engelbreth-Holm-Swarm (EHS) Hydrogel mimicking the extracellular matrix (ECM) basement membrane. Chemically cross-linked gelatin methacryloyl (GelMA) was used to form the conduit backbone, while EHS Hydrogels improved nerve fiber growth while shortening repair time. Statistical significant difference had been found between the blank conduit and the composite conduit group on compound muscle action potential after 4 months. On the other hand, results between the composite conduit group and the autograft group were of no statistical differences. All results above showed that the composite conduit filled with EHS Hydrogel can promote the repair of peripheral nerve and may become a promising way to treat peripheral nerve defects.

3D printed titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment and its bone regeneration study.

Biofabrication of personalized titanium scaffold mimicking that of the osteocyte microenvironment is challenging due to its complex geometrical cues. The effect of scaffolds geometrical cues and implantation sites on osteogenesis is still not clear. In this study, personalized titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment were precisely designed and fabricated by selected laser melting method. The effects of different geometric cues, including porosity, pore sizes and interconnection properties, on cellular behavior were investigated. Biomimetic mechanical properties of porous titanium alloy scaffold were predesigned and simulated by finite element analysis.In vitroexperiment revealed that homogeneous diamond-like structures mimicking that of the osteocyte microenvironment triggered osteocyte adhesion and migration behavior. Typical implantation sites, including rabbit femur, beagle femur, and beagle skull, were used to study the implantation sites effects on bone regeneration.In vivoexperimental results indicated that different implantation sites showed significant differences. This study helps to understand the scaffolds geometrical microenvironment and implantation sites effects on osteogenesis mechanism. And it is beneficial to the development of bone implants with better bone regeneration ability.

Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles.

PURPOSE: Honokiol showed potential application in cancer treatment, but its poor water solubility restricts its clinical application greatly. So, we designed a self-assembled monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelle to load honokiol to overcome its poor water solubility. METHODS: We synthesized MPEG-PCL diblock copolymer that could self-assemble into monodisperse micelles at the particle size of ca.18 nm in water. Honokiol was loaded into MPEG-PCL micelle by direct dissolution method assisted by ultrasound, without any surfactants, organic solvents, and vigorous stirring. RESULTS: The blank MPEG-PCL micelles (100 mg/mL) did not induce any hemolysis in vitro and showed very low toxicity ex vivo and in vivo. Honokiol could be molecularly incorporated into MPEG-PCL micelles at the drug loading of about 20% by direct dissolution method assisted by ultrasound. After loaded into MPEG-PCL micelles, honokiol maintained its molecular structure and anticancer activity in vitro. Honokiol could be sustained released from MPEG-PCL micelles in vitro. The honokiol loaded MPEG-PCL micelles could be lyophilized without any adjuvant. CONCLUSION: The prepared honokiol formulation based on self-assembled MPEG-PCL micelle was stable, safe, effective, easy to produce and scale up, and showed potential clinical application.

Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel.

In this work, a series of biodegradable triblock poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers were successfully synthesized by ring-opening copolymerization, and were characterized by (1)H NMR, FT-IR, GPC, and DSC. Aqueous solutions of PECE copolymers underwent thermosensitive sol-gel-sol transition as temperature increases when the concentration was above corresponding critical gel concentration (CGC). Sol-gel-sol phase transition diagrams were recorded using test tube inverting method, which depended on hydrophilic/hydrophobic balance in macromolecular structure, as well as some other factors, including topology of triblock copolymers and solution composition of the hydrogel. As a result, the sol-gel-sol transition temperature range could be varied, which might be very useful for its application as injectable drug delivery systems. The in vivo gel formation and degradation behavior was conducted by injecting aqueous PECE solution into KunMing mice subcutaneously. In vitro degradation behavior, in vitro drug release behavior, and cytotoxicity were also investigated in this paper. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PECE hydrogel is believed to be promising for in situ gel-forming controlled drug delivery system.

Targeted nanoparticle-mediated LHPP for melanoma treatment.

Background: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effective gene delivery systems. Methods: A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a LHPP plasmid, forming an iDPP/LHPP nanocomplex. The iDPP/LHPP nanocomplex was characterized by particle size distribution, zeta potential, morphology, cytotoxicity, and transfection efficiency. The antitumor efficacy of the nanocomplex against melanoma was studied both in vitro and in vivo. Further, the potential epigenetic changes in melanoma induced by iDPP/LHPP nanocomplex were evaluated. Results: The iDPP/LHPP nanocomplex showed high transfection efficiency and low toxicity. Moreover, the nanocomplex displayed a neutral charge that can meet the requirement of intravenous injection for targeted gene therapy. In vitro and in vivo experiments indicated that the iDPP/LHPP nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that LHPP played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription. Conclusion: This work demonstrates that the iDPP nanoparticle-delivered LHPP gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.

Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair.

Nerve conduits provide an advanced tool for repairing the injured peripheral nerve that often causes disability and mortality. Currently, the efficiency of conduits in repairing peripheral nerve is unsatisfying. Here, we show a functional nanoparticle-enhanced nerve conduit for promoting the regeneration of peripheral nerves. This conduit, which consists of gelatin-methacryloyl (GelMA) hydrogels with drug loaded poly(ethylene glycol)- poly(3-caprolactone) (MPEG-PCL) nanoparticles dispersed in the hydrogel matrix, is rapidly fabricated by a continuous three-dimensional (3D) printing process. While the 3D-printed hydrogel conduit with customized size, shape and structure provides a physical microenvironment for axonal elongation, the nanoparticles sustained release the drug to facilitate the nerve regeneration. The drug, 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino) benzenesulfonamide, is a Hippo pathway inhibitor with multiple functions including improving the proliferation and migration of Schwann cells and up-regulating neurotrophic factors genes. The descried functional nerve conduit efficiently induced the recovery of sciatic injuries in morphology, histopathology and functions in vivo, showing the potential clinical application in peripheral nerve repair. STATEMENTS OF SIGNIFICANCE: Functional nerve conduit provides a promising strategy alternative to autografts. In this work, we rapidly customized a nanoparticle-enhanced conduit by the continuous bioprinting process. This nanoparticle in the conduit can release a Hippo pathway inhibitor to facilitate the nerve regeneration and function restoration. The efficacy of the conduits is comparable to that of autograft, suggesting the potential clinical applications.

Basic fibroblast growth factor loaded biodegradable PCL-PEG-PCL copolymeric nanoparticles: preparation, in vitro release and immunogenicity study.

In this article, human basic fibroblast growth factor (bFGF) loaded PCL-PEG-PCL (PCEC) nanoparticles were prepared by modified W1/O/W2 double emulsion solvent evaporation method. The bFGF encapsulated in PCEC nanoparticles could be released in sustained release behavior in vitro. After subcutaneous single-dose injection of bFGF loaded PCEC nanoparticles at 20 microg of bFGF per dose in mice, the anti-bFGF special autoantibody IgG continued to grow until 8 weeks after the immunization and was still kept at high level at week 11. At the same time, HK293 cell viability assay in vitro indicated that the cytotoxicity of blank PCEC nanoparticles was low but dose dependent. For some success in controlling tumor growth had been met by neutralizing bFGF reported previously, the bFGF loaded PCEC nanoparticles prepared in this paper might have potential application as anti-tumor vaccine.

A novel injectable local hydrophobic drug delivery system: Biodegradable nanoparticles in thermo-sensitive hydrogel.

In this article, a novel local hydrophobic drug delivery system: nanoparticles in thermo-sensitive hydrogel, was demonstrated. First, honokiol, as a model hydrophobic drug, loaded poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) nanoparticles were prepared by emulsion solvent evaporation method, and then were incorporated into thermo-sensitive F127 hydrous matrix. The obtained injectable hydrophobic drug delivery system can act as a depot for sustained release of honokiol in situ. The lower critical solution temperature (LCST) of the composite matrix increases with increase in the mass of incorporated nanoparticles, or with decrease in the amount of residual organic solvent in the system. Honokiol release profile in vitro was studied, and the results showed that honokiol could be sustained released from the system. The described injectable drug delivery system might have great potential application for local delivery of hydrophobic drugs such as honokiol.

Preparation of mannan modified anionic PCL-PEG-PCL nanoparticles at one-step for bFGF antigen delivery to improve humoral immunity.

In this article, blank anionic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) and anionic mannan modified PCEC (MPCEC) nanoparticles with nearly the same particle size and zeta potential were prepared by emulsion solvent evaporation method. Human basic fibroblast growth factor (bFGF) was absorbed onto anionic nanoparticles surface due to electrostatic interaction. The obtained bFGF-nanoparticles complexes were injected subcutaneously into C57BL/6 mice at 20 microg of bFGF/dose on week 0, 1, 2 and 3. The mice serum was collected on week 4, and bFGF-specific autoantibody total IgG, IgG1 and IgG2a titer in serum was determined by ELISA. The results indicated that the autoantibody IgG, IgG1 and IgG2a titer of the mice immunized by bFGF-MPCEC complexes were higher than that immunized by either bFGF-PCEC or bFGF-Alum. This phenomenon might be due to that mannan functionalized MPCEC nanoparticles could be targeted to dendritic cells (DCs) to improve humoral immunity. The prepared anionic mannan modified PCEC nanoparticles (MPCEC) might have great potential application in vaccine delivery systems.