Improved Cancer Immunochemotherapy via Optimal Co-delivery of Chemotherapeutic and Immunomodulatory Agents.

Abstract:

:It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX). Although antitumor immune responses were enhanced with a PTX-loaded nanocarrier, the accumulation of myeloid-derived suppressor cells (MDSCs) was also significantly increased, which may limit the overall efficacy of therapy. In the present work, we developed an improved dual-functional nanocarrier (PEG5k-Fmoc-NLG2) to co-load PTX and sunitinib (SUN, a multitarget receptor tyrosine kinase inhibitor) for improved cancer immunochemotherapy. We found that the recruited MDSCs negatively impacted the overall antitumor activity of the PTX-loaded PEG-NLG nanocarrier. Mechanistic study suggests that this is likely attributed to the PTX-mediated induction of a number of chemokines that are involved in the recruitment of MDSCs. We have further shown that the induction of these chemokines was drastically blocked by SUN. Co-delivery of PTX and SUN via the PEG5k-Fmoc-NLG9192 nanocarrier led to a further improvement in the therapeutic efficacy with a concomitant reduction in MDSCs.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Chen Y,Sun J,Huang Y,Lu B,Li S

doi

10.1021/acs.molpharmaceut.8b00717

subject

Has Abstract

pub_date

2018-11-05 00:00:00

pages

5162-5173

issue

11

eissn

1543-8384

issn

1543-8392

journal_volume

15

pub_type

杂志文章
  • Heat Treatment of Poloxamer-Stabilized Triglyceride Nanodispersions: Effects and Underlying Mechanism.

    abstract::Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized trimyristin nanoemulsion resulted in moderate...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00202

    authors: Göke K,Roese E,Bunjes H

    更新日期:2018-08-06 00:00:00

  • Selective Photokilling of Colorectal Tumors by Near-Infrared Photoimmunotherapy with a GPA33-Targeted Single-Chain Antibody Variable Fragment Conjugate.

    abstract::Antibody-based near-infrared photoimmunotherapy (NIR-PIT) is an attractive strategy for cancer treatment. Tumor cells can be selectively and efficiently killed by the targeted delivery of an antibody-photoabsorber complex followed by exposure to NIR light. Glycoprotein A33 antigen (GPA33) is highly expressed in most h...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00210

    authors: Wei D,Tao Z,Shi Q,Wang L,Liu L,She T,Yi Q,Wen X,Liu L,Li S,Yang H,Jiang X

    更新日期:2020-07-06 00:00:00

  • Assessment of a modular transfection system based upon cellular localization of DNA.

    abstract::Delivery of plasmid DNA for protein production in mammalian cells is not an efficient process. In this study, the theory that cellular localization of plasmid DNA increases transfection efficiency is examined with an emphasis on the understanding of the cellular association of the components of a ternary transfection ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp049969a

    authors: Guo C,Gemeinhart RA

    更新日期:2004-07-01 00:00:00

  • Dry hybrid lipid-silica microcapsules engineered from submicron lipid droplets and nanoparticles as a novel delivery system for poorly soluble drugs.

    abstract::We report on the fabrication and characterization of dry hybrid lipid-silica nanoparticle based microcapsules with an internal porous matrix structure for encapsulation of poorly soluble drugs, and their delivery properties (in vitro release and lipolysis and in vivo pharmacokinetics demonstrated for indomethacin as a...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp900063t

    authors: Simovic S,Heard P,Hui H,Song Y,Peddie F,Davey AK,Lewis A,Rades T,Prestidge CA

    更新日期:2009-05-01 00:00:00

  • Application of in silico, in vitro and preclinical pharmacokinetic data for the effective and efficient prediction of human pharmacokinetics.

    abstract::In the present age of pharmaceutical research and development, focused delivery of decision making data is more imperative than ever before. Resulting from several years' success, failure and consequential learning, this article also proffers advice and guidance on which in vitro and in vivo experiments to perform to ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300476z

    authors: Grime KH,Barton P,McGinnity DF

    更新日期:2013-04-01 00:00:00

  • Diels-Alder Hydrogels for Controlled Antibody Release: Correlation between Mesh Size and Release Rate.

    abstract::Eight-armed PEG, molecular mass 10 kDa, was functionalized with furyl and maleimide groups, respectively; the obtained macromonomers were cross-linked via Diels-Alder chemistry. The mesh size (ξ) of the prepared hydrogels was determined by swelling studies, rheology, and low field NMR spectroscopy. The in vitro releas...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00375

    authors: Kirchhof S,Abrami M,Messmann V,Hammer N,Goepferich AM,Grassi M,Brandl FP

    更新日期:2015-09-08 00:00:00

  • Genetically modified mesenchymal stem cells for improved islet transplantation.

    abstract::The use of adult stem cells for therapeutic purposes has met with great success in recent years. Among several types of adult stem cells, mesenchymal stem cells (MSCs) derived from bone marrow (BM) and other sources have gained popularity for basic research and clinical applications because of their therapeutic potent...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章,评审

    doi:10.1021/mp200135e

    authors: Wu H,Ye Z,Mahato RI

    更新日期:2011-10-03 00:00:00

  • Novel 99mTc-Labeled Glucose Derivative for Single Photon Emission Computed Tomography: A Promising Tumor Imaging Agent.

    abstract::In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with 99mTc for preparing 99mTc-CN5DG. 99mTc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00415

    authors: Zhang X,Ruan Q,Duan X,Gan Q,Song X,Fang S,Lin X,Du J,Zhang J

    更新日期:2018-08-06 00:00:00

  • Validation of Thiosemicarbazone Compounds as P-Glycoprotein Inhibitors in Human Primary Brain-Blood Barrier and Glioblastoma Stem Cells.

    abstract::P-glycoprotein (Pgp) is highly expressed on blood-brain barrier (BBB) and glioblastoma (GB) cells, particularly on cancer stem cells (SC). Pgp recognizes a broad spectrum of substrates, limiting the therapeutic efficacy of several chemotherapeutic drugs in eradicating GB SC. Finding effective and safe inhibitors of Pg...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b00018

    authors: Salaroglio IC,Abate C,Rolando B,Battaglia L,Gazzano E,Colombino E,Costamagna C,Annovazzi L,Mellai M,Berardi F,Capucchio MT,Schiffer D,Riganti C

    更新日期:2019-08-05 00:00:00

  • Oxidative stress induced by copper and iron complexes with 8-hydroxyquinoline derivatives causes paraptotic death of HeLa cancer cells.

    abstract::Here, we report the antiproliferative/cytotoxic properties of 8-hydroxyquinoline (8-HQ) derivatives on HeLa cells in the presence of transition metal ions (Cu(2+), Fe(3+), Co(2+), Ni(2+)). Two series of ligands were tested, the arylvinylquinolinic L1-L8 and the arylethylenequinolinic L9-L16, which can all interact wit...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400592n

    authors: Barilli A,Atzeri C,Bassanetti I,Ingoglia F,Dall'Asta V,Bussolati O,Maffini M,Mucchino C,Marchiò L

    更新日期:2014-04-07 00:00:00

  • Therapeutic delivery of siRNA silencing HIF-1 alpha with micellar nanoparticles inhibits hypoxic tumor growth.

    abstract::The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxi...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300193f

    authors: Liu XQ,Xiong MH,Shu XT,Tang RZ,Wang J

    更新日期:2012-10-01 00:00:00

  • Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer.

    abstract::PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate en...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00310

    authors: Singh Y,Durga Rao Viswanadham KK,Kumar Jajoriya A,Meher JG,Raval K,Jaiswal S,Dewangan J,Bora HK,Rath SK,Lal J,Mishra DP,Chourasia MK

    更新日期:2017-08-07 00:00:00

  • PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection.

    abstract::PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulatio...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00118

    authors: Cayatte C,Marin A,Rajani GM,Schneider-Ohrum K,Snell Bennett A,Marshall JD,Andrianov AK

    更新日期:2017-07-03 00:00:00

  • Hydrophobically Modified Polymer/α-Cyclodextrin Thermoresponsive Hydrogels for Use in Ocular Drug Delivery.

    abstract::We report herein on the preparation of thermoresponsive hydrogels by taking advantage of the interaction of cyclodextrins (CDs) and a hydrophobically modified polymer. A hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC) gel formed thermoresponsive hydrogels when small amounts of α-CD were added to the s...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00291

    authors: Iohara D,Okubo M,Anraku M,Uramatsu S,Shimamoto T,Uekama K,Hirayama F

    更新日期:2017-08-07 00:00:00

  • Influence of charge and steric bulk in the C-24 region on the interaction of bile acids with human apical sodium-dependent bile acid transporter.

    abstract::The human apical sodium-dependent bile acid transporter (hASBT) is a potential target for drug delivery, but an understanding of hASBT substrate requirements is limited. The objective of this study was to evaluate the influence of ionic character and steric bulk in the C-24 region of bile acid conjugates in governing ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp0600135

    authors: Balakrishnan A,Wring SA,Coop A,Polli JE

    更新日期:2006-05-01 00:00:00

  • Dual Functional Peptide-Driven Nanoparticles for Highly Efficient Glioma-Targeting and Drug Codelivery.

    abstract::Compared with peripheral tumors, glioma is very difficult to treat, not only because it has general features of tumor but also because the therapy has been restricted by the brain-blood barrier (BBB). The two main features of tumor growth are angiogenesis and proliferation of tumor cells. RNA interference (RNAi) can d...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b00051

    authors: Kuang Y,Jiang X,Zhang Y,Lu Y,Ma H,Guo Y,Zhang Y,An S,Li J,Liu L,Wu Y,Liang J,Jiang C

    更新日期:2016-05-02 00:00:00

  • Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts.

    abstract::The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective g...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00386

    authors: Cordeiro T,Castiñeira C,Mendes D,Danède F,Sotomayor J,Fonseca IM,Gomes da Silva M,Paiva A,Barreiros S,Cardoso MM,Viciosa MT,Correia NT,Dionisio M

    更新日期:2017-09-05 00:00:00

  • Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.

    abstract::The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viabil...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp4005035

    authors: Sharma VD,Lees J,Hoffman NE,Brailoiu E,Madesh M,Wunder SL,Ilies MA

    更新日期:2014-02-03 00:00:00

  • Solubility Challenges in High Concentration Monoclonal Antibody Formulations: Relationship with Amino Acid Sequence and Intermolecular Interactions.

    abstract::The purpose of this work was to elucidate the molecular interactions leading to monoclonal antibody self-association and precipitation and utilize biophysical measurements to predict solubility behavior at high protein concentration. Two monoclonal antibodies (mAb-G and mAb-R) binding to overlapping epitopes were inve...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00336

    authors: Pindrus M,Shire SJ,Kelley RF,Demeule B,Wong R,Xu Y,Yadav S

    更新日期:2015-11-02 00:00:00

  • A novel hPepT1 stably transfected cell line: establishing a correlation between expression and function.

    abstract::Stably transfected MDCK/hPepT1-V5&His clonal cell lines expressing varying levels of epitope-tagged hPepT1 protein were established to quantify the relationship between transgene hPepT1 expression levels and its functional kinetics in facilitating peptide and peptide-like drug uptake and transport in vitro. The hPepT1...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp034011l

    authors: Herrera-Ruiz D,Faria TN,Bhardwaj RK,Timoszyk J,Gudmundsson OS,Moench P,Wall DA,Smith RL,Knipp GT

    更新日期:2004-03-01 00:00:00

  • Elucidating an Amorphous Form Stabilization Mechanism for Tenapanor Hydrochloride: Crystal Structure Analysis Using X-ray Diffraction, NMR Crystallography, and Molecular Modeling.

    abstract::By the combined use of powder and single-crystal X-ray diffraction, solid-state NMR, and molecular modeling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY, and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b01047

    authors: Nilsson Lill SO,Widdifield CM,Pettersen A,Svensk Ankarberg A,Lindkvist M,Aldred P,Gracin S,Shankland N,Shankland K,Schantz S,Emsley L

    更新日期:2018-04-02 00:00:00

  • New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma.

    abstract::In this work, we have developed covalent and low molecular weight docetaxel delivery systems based on conjugation with N-acetyl-d-galactosamine and studied their properties related to hepatocellular carcinoma cells. The resulting glycoconjugates have an excellent affinity to the asialoglycoprotein receptor (ASGPR) in ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00980

    authors: Petrov RA,Mefedova SR,Yamansarov EY,Maklakova SY,Grishin DA,Lopatukhina EV,Burenina OY,Lopukhov AV,Kovalev SV,Timchenko YV,Ondar EE,Ivanenkov YA,Evteev SA,Vaneev AN,Timoshenko RV,Klyachko NL,Erofeev AS,Gorelkin PV,Bel

    更新日期:2021-01-04 00:00:00

  • Role of surface exposed tryptophan as substrate generators for the antibody catalyzed water oxidation pathway.

    abstract::The reaction of singlet oxygen with water to form hydrogen peroxide was catalyzed by antibodies and has been termed as the antibody catalyzed water oxidation pathway (ACWOP) (Nieva and Wentworth, Trends Biochem. Sci. 2004, 29, 274-278; Nieva et al. Immunol. Lett. 2006, 103, 33-38). While conserved and buried tryptopha...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300418r

    authors: Sreedhara A,Lau K,Li C,Hosken B,Macchi F,Zhan D,Shen A,Steinmann D,Schöneich C,Lentz Y

    更新日期:2013-01-07 00:00:00

  • In vivo biodistribution of prion- and GM1-targeted polymersomes following intravenous administration in mice.

    abstract::Due to the aging of the population, the incidence of neurodegenerative diseases, such as Parkinson's and Alzheimer's, is expected to grow and, hence, the demand for adequate treatment modalities. However, the delivery of medicines into the brain for the treatment of brain-related diseases is hampered by the presence o...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp200621v

    authors: Stojanov K,Georgieva JV,Brinkhuis RP,van Hest JC,Rutjes FP,Dierckx RA,de Vries EF,Zuhorn IS

    更新日期:2012-06-04 00:00:00

  • Development of a poly(d,l-lactic-co-glycolic acid) nanoparticle formulation of STAT3 inhibitor JSI-124: implication for cancer immunotherapy.

    abstract::Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for t...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp900145g

    authors: Molavi O,Mahmud A,Hamdy S,Hung RW,Lai R,Samuel J,Lavasanifar A

    更新日期:2010-04-05 00:00:00

  • In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System.

    abstract::An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and su...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b01141

    authors: Borgheti-Cardoso LN,Kooijmans SAA,Fens MHAM,van der Meel R,Vicentini FTMC,Fantini MCA,Bentley MVLB,Schiffelers RM

    更新日期:2017-05-01 00:00:00

  • Orally Bioavailable and Effective Buparvaquone Lipid-Based Nanomedicines for Visceral Leishmaniasis.

    abstract::Nanoenabled lipid-based drug delivery systems offer a platform to overcome challenges encountered with current failed leads in the treatment of parasitic and infectious diseases. When prepared with FDA or EMA approved excipients, they can be readily translated without the need for further toxicological studies, while ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00097

    authors: Smith L,Serrano DR,Mauger M,Bolás-Fernández F,Dea-Ayuela MA,Lalatsa A

    更新日期:2018-07-02 00:00:00

  • Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    abstract::An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp5006036

    authors: Polster CS,Wu SJ,Gueorguieva I,Sperry DC

    更新日期:2015-04-06 00:00:00

  • Generation and characterization of a new solid form of trehalose.

    abstract::We have identified and characterized a new solid form of trehalose, the δ form (Tδ) using (13)C solid-state NMR spectroscopy (SSNMR). Tδ is formed from dehydrations of trehalose dihydrate (T(h)) performed at or below 100 °C, and it is generated concurrently with the α form of trehalose (Tα) and amorphous trehalose (T(...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400104b

    authors: Pyszczynski SJ,Munson EJ

    更新日期:2013-09-03 00:00:00

  • Intrinsic dynamics of DNA-polymer complexes: a mechanism for DNA release.

    abstract::The transfer of genetic material into cells using nonviral vectors offers unique potential for therapeutics; however, the efficacy of delivery depends upon a poorly understood, multistep pathway, limiting the prospects for successful gene delivery. Mechanistic insight into DNA association and release has been hampered...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3002864

    authors: Prevette LE,Nikolova EN,Al-Hashimi HM,Banaszak Holl MM

    更新日期:2012-09-04 00:00:00