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Our study aimed at studying mechanism of miR-214 packaged with lipidosome nanoparticles on prompting apoptosis of intestinal cancer through regulating p53 pathway. SW480 cells were divided into blank group, empty carrier group, agonist group and group with carrier and antagonist. The negative control group was set, and groups related to p53 pathway were set as agonist group, inhibitor group and group with antagonist and inhibitor. The effect of miR-214 packaged with lipidosome nanoparticles on proliferation and apoptosis of intestinal cancer cells and p53 pathway in intestinal cancer cells was observed. Expression level of miR-214 in group with carrier and antagonist was lower than in other groups. The proportion of active cells in the group with carrier and antagonist started to be reduced notably from the second day. There was no notable declining tendency active cells' proportion from other groups. The quantity of cell apoptosis in group with carrier and antagonist was higher than in the other groups. The expression level of cleaved Caspase-3 in the group with carrier and antagonist was notably higher than in the other groups. Moreover, expression of Bcl-2/Bax protein was reversed, while expression of p53 protein in the carrier and antagonist groups was notably higher than in the other groups. The antagonist of miR-214 packaged with lipidosome nanoparticles could target on p53 pathway. The activity of p53 pathway was reduced by miR-214, and expression of Bcl-2 was increased. The expressions levels of Bax and cleaved Caspase-3 were also reversed, and molecular mechanism was mainly related with restraining of p53 signal pathway.

Introduction: β-lactamase (LACTB) is a tumor suppressor gene in various tumors including melanoma. However, it remains challenging to efficiently deliver the LACTB gene into melanoma. Recently, we designed a nonviral nanocarrier iRGD/DOTAP/MPEG-PDLLA (iDPP) that could deliver gene targetedly to melanoma efficiently without obvious adverse effects., Methods: In this study, the tumor-targeted nanoparticle iDPP was prepared to deliver LACTB gene to treat melanoma in vitro and in vivo. First, the expression level of LACTB in 6 clinical specimens of melanoma patients was evaluated. Subsequently, the characteristics of iDPP/ LACTB nanocomplexes were studied. Afterwards, the in vitro and in vivo anti-tumor efficacy of the iDPP/ LACTB nanocomplexes were explored utilizing the B16-F10 mouse melanoma cell line and the B16-F10 subcutaneous melanoma model., Results: Compared with the normal epithelium, the expression level of LACTB in melanoma tissues was significantly downregulated. In vitro B16-F10 cell tests showed iDPP/ LACTB nanocomplexes could increase the mRNA levels of P21, Bid, Bax, Pidd1, and Sival genes and up-regulate the p53 signaling pathway of melanoma cells, thus promoting cell apoptosis and blocking the cell cycle. Injected intravenously, iDPP nanoparticles could deliver DNA to the subcutaneous melanoma targetedly. Based on in vivo mouse xenograft model, iDPP/ LACTB nanocomplexes could effectively inhibit tumor proliferation and induce tumor apoptosis, thus significantly inhibiting melanoma growth (tumor inhibition rate is about 68%) in the subcutaneous B16-F10 melanoma model., Conclusion: The downregulated LACTB might be a potential target for melanoma therapy. The iDPP/ LACTB nanocomplexes could inhibit the growth of the mouse melanoma without obvious side effects, which provide a new option for melanoma gene therapy research., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Introduction: Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency., Methods: Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy., Results: The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity., Discussion: This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy., Competing Interests: QS, YL, MS, MG, and MX have applied patents on the designed peptides in this study. The authors report no other conflicts of interest in this work., (© 2021 Sui et al.)

We report here a novel light-triggered nanosystem based on co-assembling nanoaggregates (NAs) of lipophilic photosensitizers and lipophilic prodrugs containing multiple thioethers. Upon laser irradiation, the oxidization of the multiple thioethers by photosensitizer-generated singlet oxygen could rapidly destroy the NA structure, resulting in faster drug release than those containing a single thioether.

Combination of chemotherapeutics and immunomodulators can generate synergistic anticancer efficacy, exerting efficient chemoimmunotherapy for cancer treatment. Nanoparticulate delivery systems hold great promise to promote synergistic anticancer efficacy for the codelivery of drugs. However, there remain challenges to precisely coencapsulate and deliver combinational drugs at designed ratios due to the difference of compatibility between drugs and nanocarriers. In this study, coassembled nanoparticles of lipophilic prodrugs (LPs) were designed to codeliver chemotherapeutics and immunomodulators for cancer treatment. Such nanoassemblies (NAs) could act as platforms to ratiometrically coencapsulate chemotherapeutics and immunomodulators. Based on this method, NAs formed by the self-assembly of iRGD peptide derivatives, paclitaxel (PTX) LPs, and imiquimod (R837) LPs were demonstrated to target the tumor at unified pharmacokinetics, further inducing the effective tumor inhibition and tumor recurrence prevention. This work provided an alternative to prepare chemoimmunotherapeutic NAs with advantages of ratiometric drug coencapsulation and unified pharmacokinetics, which may advance the future cancer chemoimmunotherapy.

Nanoassemblies (NAs) of small-molecule lipophilic prodrugs have been widely investigated for efficient drug delivery in cancer therapy, but their kinetic stability has not attracted sufficient attention in the past studies. Herein, we reported that kinetic stability has a great influence on the drug release from the NAs of lipophilic prodrugs in physiologically relevant media. Based on the co-assembled FRET nanosystems of two lipophilic fluorescent prodrugs, we demonstrated that NAs constructed by lipophilic prodrugs containing shorter alkyl chains or those with higher unsaturated degrees displayed poorer kinetic stability, which further resulted in remarkably faster drug release in mouse plasma and various tissue homogenates. More importantly, these kinetically unstable NAs also induced rapid intracellular drug release, resulting in much more potent cytotoxicity. These findings highlight the crucial role of kinetic stability in determining the drug release from the NAs of lipophilic prodrugs, which would effectively guide their rational designs for cancer therapy.

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., Competing Interests: The authors report no conflicts of interest in this work.

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., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Gene therapy is emerging as a promising tool for cancer treatment. Down-regulation of survivin gene can lead to the cancer inhibition. However, the lack of efficient and safe gene delivery system is still a critical obstacle to clinical gene therapy. In this study, we use a biodegradable nanoparticle to deliver human survivin-T34A ( T34A ) to dominant-negatively regulate survivin gene for ovarian cancer therapy. This nanoparticle, self-assembled from monomethoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA) copolymer and N -[1-(2,3-dioleoyloxy) propyl]- N , N , N -trimethylammonium chloride (DOTAP), has high transfection capability and negligible cytotoxicity. The nanoparticle-delivered T34A gene can efficiently inhibit the growth of SKOV3 ovarian cancer cells through induction of apoptosis in vitro . After intraperitoneal injection, the nanoparticle-delivered T34A gene significantly inhibited the growth of intraperitoneal metastasis of SKOV3 ovarian cancer, with no obvious adverse effects. Our data suggest that the nanoparticle-delivered T34A gene has promising clinical applications in ovarian cancer treatment.

Background: Melittin, the main active peptide ingredient of bee venom, can cause severe cell membrane lysis due to its robust interaction with negatively charged phospholipids. So far, no effective anti-melittin vaccine has been developed to protect people from undesired melittin intoxication., Methods: Herein, we prepared a polydiacetylene (PDA) nanoparticle with cell membrane-mimic surface to complex melittin, forming an anti-melittin vaccine (PDA-melittin)., Results: PDA nanoparticles could effectively combine with melittin and neutralize its toxicity. PDA-melittin nanocomplex is demonstrated to enhance melittin uptake by DCs and stimulate strong melittin-specific immunity. Mice immunized with PDA-melittin nanocomplex showed higher survival rate after exposion to melittin than untreated mice., Conclusion: The PDA-melittin nanocomplex can efficiently and safely generate a specific immunity against melittin to protect body from melittin intoxication, providing a new method with potential clinical application for the treatment of melittin intoxication., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

A facile one-pot synthetic strategy was explored to synthesize carbon/calcium phosphate/Fe3O4 composite nanoparticles (carbon/CaP/Fe3O4 composite NPs). Taking advantage of the unique structure including mesoporous, small CaP and Fe3O4 subunits homogeneously distributed in a carbon matrix, carbon/CaP/Fe3O4 NPs integrate high drug loading, pH/NIR-sensitive, photothermal and magnetic properties into one nanoplatform for cancer theranostics.

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin-polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy.

Rationally designed nanoparticles that can bind toxins show great promise for detoxification. However, the conventional intravenous administration of nanoparticles for detoxification often leads to nanoparticle accumulation in the liver, posing a risk of secondary poisoning especially in liver-failure patients. Here we present a liver-inspired three-dimensional (3D) detoxification device. This device is created by 3D printing of designer hydrogels with functional polydiacetylene nanoparticles installed in the hydrogel matrix. The nanoparticles can attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently. Our results show that the toxin solution completely loses its virulence after treatment using this biomimetic detoxification device. This work provides a proof-of-concept of detoxification by a 3D-printed biomimetic nanocomposite construct in hydrogel, and could lead to the development of alternative detoxification platforms.

Some bladder disease therapies can benefit from intravesical drug delivery, which involves direct instillation of drug into the bladder via a catheter, to attain high local concentrations of the drug with minimal systemic effects. Deguelin is a potential anticancer agent, however, its poor water solubility and neurotoxicity restrict its clinical application. To address these challenges, we investigated the promising application of deguelin in the intravesical therapy of bladder cancer by designing a novel intravesical drug delivery system for deguelin. It was found that deguelin could efficiently kill bladder cancer cells and inhibit angiogenesis. Intravesically administrated deguelin had better tolerance than systemically applied deguelin. Encapsulation of deguelin in cationic DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) hybrid nanoparticles (DMP) created the deguelin loaded DMP nanoparticles (D/DMP). They had a mean particle size of 35 nm and zeta potential of 21 mV, rendering deguelin completely dispersible in aqueous media. Encapsulation of deguelin in cationic DMP nanoparticles enhanced the anticancer activity of deguelin in vitro. In addition, D/DMP nanoparticles were incorporated into a thermo-sensitive Pluronic F127 hydrogel, forming a novel D/DMP-F system, which remained in a flowing liquid state at lower than 25 °C, but underwent gelation at higher temperatures. The DMP nanoparticles in the F127 hydrogel system (DMP-F) could significantly extend the hydrophobic drug residence time and increase the drug concentration within the bladder. These results suggested that DMP-F was a good intravesical drug delivery system and D/DMP-F may have promising applications in intravesical therapy of bladder cancer.

Nanotechnology provides researchers with new tools for cancer treatment. Biodegradable polymeric nanoparticles, as an advanced drug delivery system, have promising applications in cancer treatment. Poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymers are biodegradable and amphiphilic, and show potential application in drug delivery. In recent years, PCL/PEG copolymeric nanoparticles, as a potential nanoplatform for anticancer agent delivery, received increasing attention. This paper reviews PCL/PEG copolymer nanoparticles for anticancer agent delivery, including overcoming water insolubility of hydrophobic drug, targeting chemotherapeutic drug to tumor, and delivering genes, vaccines, and diagnostic agents.

Background: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose., Methods and Results: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis., Conclusion: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.

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.

In this article, we demonstrated a novel injectable polymer matrix: honokiol (HK) loaded poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel for the drug local delivery. First, HK, as a model hydrophobic drug, was loaded into PCL-PEG-PCL nanoparticles by emulsion solvent evaporation method to overcome its poor water solubility. Then, the HK-loaded PCEC nanoparticles (HK-PCEC) were incorporated into thermosensitive PEG-PCL-PEG hydrogel, which was sol at low temperature and could gel as a depot for sustained release of drug in situ after topical injection. The HK-PCEC incorporated PECE hydrogel (HK-PCEC-PECE) was biodegradable and could be gradually eliminated from the injection site in about 2 weeks after subcutaneously injected into mice. The in vitro release studies indicated that HK could be released from HK-PCEC and HK-PCEC-PECE in a sustained manner. Such biodegradable smart drug-delivery system might have great potential application in injectable hydrophobic drug local delivery system.

Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by (1)H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG-PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG-PLA nanoparticles in this paper might be a novel formulation for honokiol delivery., (Copyright 2009 Elsevier B.V. All rights reserved.)

Honokiol (HK) can efficiently inhibit the growth of tumors. However, its clinical applications have been restricted by its extreme hydrophobicity. We hope to improve its water solubility by nanotechnology. And we wonder whether a novel honokiol nanoparticles-loaded thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel (HK-hydrogel) could improve the therapeutic efficacy on malignant pleural effusion (MPE). To evaluate the therapeutic effects of HK-hydrogel on MPE, MPE-bearing mice were administered intrapleurally with HK-hydrogel, HK nanoparticles (HK-NP), blank hydrogel, or normal saline (NS) at days 4 and 11 after Lewis lung carcinoma (LLC) cells inoculation, respectively. Pleural tumor foci and survival time were observed, and antiangiogenesis of HK-hydrogel was determined by CD31. Histological analysis and assessment of apoptotic cells were also conducted in tumor tissues. HK-hydrogel reduced the number of pleural tumor foci, while prolonging the survival time of MPE-bearing mice, more effectively, as compared with control groups. In addition, HK-hydrogel successfully inhibited angiogenesis as assessed by CD31 (P < 0.05). Histological analysis of pleural tumors exhibited that HK-hydrogel led to the increased rate of apoptosis. This work is important for the further application of HK-hydrogel in the treatment of MPE.

Biodegradable poly(epsilon-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer nanoparticles showed potential application in drug delivery systems. In this article, monodisperse poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) (PCL/PEG/PCL, PCEC) nanoparticles, approximately 40 nm, were prepared by solvent extraction method using acetone as the organic solvent. These PCL/PEG/PCL nanoparticles did not induce hemolysis in vitro and did not show toxicity in vitro or in vivo. The prepared PCL/PEG/PCL nanoparticles were employed to load doxorubicin by a pH-induced self-assembly method. In vitro release study indicated that doxorubicin release from nanoparticles at pH 5.5 was faster than that at pH 7.0. The encapsulation of doxorubicin in PCL/PEG/PCL nanoparticles enhanced the cytotoxicity of doxorubicin on a C-26 cell line in vitro. Meanwhile, compared with free doxorubicin, doxorubicin in nanoparticles could more efficiently treat mice bearing subcutaneous C-26 tumors. The doxorubicin-loaded PCL/PEG/PCL nanoparticles might be a novel doxorubicin formulation for cancer therapy.

In this article, poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone) (PCFC) copolymer was synthesized by ring-opening polymerization and characterized by 1H-NMR and GPC. Cationic PCFC nanoparticles were prepared at one-step by modified emulsion solvent evaporation method using cetyltrimethylammonium bromide as the stabilizer. The cytotoxicity of PCFC nanoparticles was studied here with and without serum. The obtained cationic PCFC nanoparticles were employed to condense and adsorb DNA onto its surface. And it could protect plasmid GFP (pGFP) from enzymatic degradation and acidic degradation in a certain period. Release behavior of pGFP from the pGFP/PCFC nanoparticles complex was also studied in vitro. The obtained cationic PCEC nanoparticles might have great potential application in DNA delivery.

In this article, a novel composite drug delivery system, honokiol nanoparticles in biodegradable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP), was prepared. CS/beta-GP solution was liquid at room temperature and turned into gel as temperature increased. With increase in beta-GP concentration, the sol-gel transition temperature decreased accordingly. Honokiol nanoparticles with diameter of about 30 nm were prepared by emulsion solvent evaporation method. The sol-gel transition temperature of CS/beta-GP system decreased as F-127 presented in honokiol nanoparticles. In vitro release profiles were studied, the results showed that honokiol could be slowly released from CS/beta-GP gel over at least 2 weeks and the release rate was greatly influenced by initial drug loading. The described injectable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP) might have potential application as local drug delivery for honokiol.

Biodegradable polyetherester copolymer (PCL/PEG/PCL, PCEC) was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene glycol) (PEG). The PCEC nanoparticles were prepared by solvent diffusion method or w/o/w double emulsion method. The obtained particles' morphology was observed on scanning electron microscopy, and the particle size distribution was determined using Malvern laser particle sizer. Bovine serum albumin was used as the model water-soluble protein drug, which was successfully encapsulated in PCEC nanoparticles, the drug release behavior was studied in detail. The hydrolytic degradation behavior of the PCEC nanoparticles was also studied.

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.

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.

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.

Xun Jin,1 Peilan Zhang,1 Li Luo,1 Hao Cheng,1 Yunzu Li,1 Ting Du,1 Bingwen Zou,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Thoracic Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. Keywords: bladder cancer, drug delivery, nanoparticles, intravesical therapy

Xun Jin,1,* Bingwen Zou,2,* Li Luo,1,* Chuanhong Zhong,3 Peilan Zhang,1 Hao Cheng,1 Yanfang Guo,1 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 2Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, 3Department of Neurosurgery, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer chemotherapy can benefit from the combination of different anticancer drugs. Here, we prepared doxorubicin (Dox)- and thioridazine (Thio)-coloaded methoxy poly(ethylene glycol)-poly(L-lactic acid) (MPEG-PLA) nanoparticles (NPs) for breast cancer therapy. These NPs have an average particle size of 27 nm. The drug loading efficiencies of Thio and Dox are 4.71% and 1.98%, respectively. Compared to the treatment of Thio or Dox alone, the combination of Thio and Dox exhibited a synergistic effect in inhibiting the growth of 4T1 breast cancer cells in vitro. In addition, the Thio- and Dox-coloaded MPEG-PLA NPs could efficiently suppress the growth of breast cancer cells in vivo. This study suggests that Thio- and Dox-coloaded MPEG-PLA NPs might have potential applications in breast cancer treatment. Keywords: thioridazine, doxorubicin, codelivery, nanoparticles, breast cancer

Background: Infiltration of a long-lasting anaesthetic is helpful during the post-operative period. The recently developed local drug delivery system, biodegradable nanoparticles in a thermo-sensitive hydrogel (nanogel system), may possibly provide an extended duration of drugs. Therefore, we evaluated whether prolonged infiltration anaesthesia could be achieved by loading lidocaine into this delivery system. Methods: Thirty male rats were randomized into five groups of six rats each: saline; 2% hydrochloride lidocaine solution; lidocaine-loaded nanogel system and its compositing formulations, namely lido–nano gel; lido–nano; and lidogel. Durations of local anaesthesia with subcutaneously injected agents were measured by tail flick latency tests in a randomized, blind fashion. Results: Lido–nano gel produced effective anaesthesia for 360±113 min, compared with 150±33 min by lidogel, 180±37 min by lido–nano, and 110±45 min by lidocaine solution ( P<0.001, means±SD), and elicited complete sensory blockade for 300±114 min, compared with 75±37 min by lidogel, 105±53 min by lido–nano, and 60±33 min by lidocaine solution ( P<0.001, means±SD) without severe skin/systemic toxicity. Conclusion: Lidocaine-loaded biodegradable nanoparticles in hydrogel produced prolonged infiltration anaesthesia in rats without severe toxicity, indicating a possible way to develop long-lasting local anaesthetics. [ABSTRACT FROM AUTHOR]