Tailored Polymers with Complement Activation Ability To Improve Antitumor Immunity.

Abstract:

:The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (COOH-PEOz-PLA). The copolymer self-assembled into micelles with hydroxyl groups shielding on the surface, which activated the complement system for the enhanced immune responses. Compared with the control nanoparticles (OCH3-NPs), COOH-NPs significantly enhanced lymph node-resident dendritic cell maturation, antigen-specific IgG production, antigen-specific CD4+ and CD8+ T-cell activation, and the amount of memory T-cell generation in vivo. Furthermore, immunization with COOH-NPs/OVA in E.G7-OVA tumor-bearing mice not only remarkably inhibited tumor growth but also prolonged the survival of tumor-bearing mice. These results indicated that COOH-NPs with the capability of complement activation efficiently boosted the immune responses for the antitumor effect. The study demonstrated the significance of taking advantage of a complement-activating vaccine platform for cancer immunotherapy.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Li C,Lu Y,Chen Q,Hu H,Zhao X,Qiao M,Chen D

doi

10.1021/acs.molpharmaceut.9b00195

subject

Has Abstract

pub_date

2019-06-03 00:00:00

pages

2648-2660

issue

6

eissn

1543-8384

issn

1543-8392

journal_volume

16

pub_type

杂志文章
  • In vivo and in silico pharmacokinetics and biodistribution of a melanocortin receptor 1 targeted agent in preclinical models of melanoma.

    abstract::The melanocortin 1 receptor (MC1R) is overexpressed in most melanoma metastases, making it a promising target for imaging of melanomas. In this study, the expression of MC1R in a large fraction of patients with melanoma was confirmed using mRNA and tissue microarray. Here, we have characterized the in vivo tumor and t...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400222j

    authors: Tafreshi NK,Silva A,Estrella VC,McCardle TW,Chen T,Jeune-Smith Y,Lloyd MC,Enkemann SA,Smalley KS,Sondak VK,Vagner J,Morse DL

    更新日期:2013-08-05 00:00:00

  • Molecular Computations of Preferential Interaction Coefficients of IgG1 Monoclonal Antibodies with Sorbitol, Sucrose, and Trehalose and the Impact of These Excipients on Aggregation and Viscosity.

    abstract::Preferential interactions of formulation excipients govern their overall interactions with protein molecules, and molecular dynamics simulations allow for the examination of the interactions at the molecular level. We used molecular dynamics simulations to examine the interactions of sorbitol, sucrose, and trehalose w...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b00545

    authors: Cloutier T,Sudrik C,Mody N,Sathish HA,Trout BL

    更新日期:2019-08-05 00:00:00

  • Laulimalide and synthetic laulimalide analogues are synergistic with paclitaxel and 2-methoxyestradiol.

    abstract::Some of the most significant therapeutic leads and agents used for the treatment of cancer target microtubule dynamics. Paclitaxel is an exceptional example that is currently used for treating a wide range of tumors. New, non-taxane microtubule stabilizers, including several epothilones, are advancing through clinical...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp060016h

    authors: Clark EA,Hills PM,Davidson BS,Wender PA,Mooberry SL

    更新日期:2006-07-01 00:00:00

  • An investigation into the dissolution properties of celecoxib melt extrudates: understanding the role of polymer type and concentration in stabilizing supersaturated drug concentrations.

    abstract::In this study, the dissolution properties of celecoxib (CX) solid dispersions manufactured from Eudragit 4155F and polyvinylpyrrolidone (PVP) were evaluated. Hot-melt extrusion (HME) technology was used to prepare amorphous solid dispersions of drug/polymer binary systems at different mass ratios. The drug concentrati...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp200157b

    authors: Abu-Diak OA,Jones DS,Andrews GP

    更新日期:2011-08-01 00:00:00

  • Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

    abstract::To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a mo...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400514t

    authors: Guo Y,Chu M,Tan S,Zhao S,Liu H,Otieno BO,Yang X,Xu C,Zhang Z

    更新日期:2014-01-06 00:00:00

  • Using Polar Ion-Pairs to Control Drug Delivery to the Airways of the Lungs.

    abstract::The rapid absorptive clearance of drugs delivered to the airways of the lungs means that many inhaled medicines have a short duration of action. The aim of this study was to investigate whether forming polar ion-pairs can modify drug absorption to slow down clearance from the airways. Salbutamol was used as a model dr...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b01166

    authors: Dutton B,Woods A,Sadler R,Prime D,Barlow DJ,Forbes B,Jones SA

    更新日期:2020-05-04 00:00:00

  • Inflammation Caused by Nanosized Delivery Systems: Is There a Benefit?

    abstract::Secondary macrophage cytotoxicity induced by nanoparticles was described before. The study aim was to investigate the role of secondary cytotoxic effect in a macrophage-lung cancer coculture model after nanoparticle treatment in the presence and absence of anti-inflammatory drugs. An in vitro coculture model composed ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b00530

    authors: Sarfraz M,Roa W,Bou-Chacra N,Löbenberg R

    更新日期:2016-09-06 00:00:00

  • Target delivery and cell imaging using hyaluronic acid-functionalized graphene quantum dots.

    abstract::This work demonstrates the way to achieve efficient and target specific delivery of a graphene quantum dot (GQD) using hyaluronic acid (HA) (GQD-HA) as a targeting agent. HA has been anchored to a GQD that accepts the fascinating adhesive properties of the catechol moiety, dopamine hydrochloride, conjugated to HA, whi...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400219u

    authors: Abdullah-Al-Nahain,Lee JE,In I,Lee H,Lee KD,Jeong JH,Park SY

    更新日期:2013-10-07 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

  • Evaluating 225Ac and 177Lu Radioimmunoconjugates against Antibody-Drug Conjugates for Small-Cell Lung Cancer.

    abstract::Interest in the use of 225Ac for targeted alpha therapies has increased dramatically over the past few years, resulting in a multitude of new isotope production and translational research efforts. However, 225Ac radioimmunoconjugate (RIC) research is still in its infancy, with most prior experience in hematologic mali...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00703

    authors: Lakes AL,An DD,Gauny SS,Ansoborlo C,Liang BH,Rees JA,McKnight KD,Karsunky H,Abergel RJ

    更新日期:2020-11-02 00:00:00

  • Predictable Heating and Positive MRI Contrast from a Mesoporous Silica-Coated Iron Oxide Nanoparticle.

    abstract::Iron oxide nanoparticles have great potential as diagnostic and therapeutic agents in cancer and other diseases; however, biological aggregation severely limits their function in vivo. Aggregates can cause poor biodistribution, reduced heating capability, and can confound their visualization and quantification by magn...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00866

    authors: Hurley KR,Ring HL,Etheridge M,Zhang J,Gao Z,Shao Q,Klein ND,Szlag VM,Chung C,Reineke TM,Garwood M,Bischof JC,Haynes CL

    更新日期:2016-07-05 00:00:00

  • Quantitative Imaging of the Hypoxia-Related Marker CAIX in Head and Neck Squamous Cell Carcinoma Xenograft Models.

    abstract::Tumor hypoxia plays a major role in radio- and chemotherapy resistance in solid tumors. Carbonic Anhydrase IX (CAIX) is an endogenous hypoxia-related protein, which is associated with poor patient outcome. The quantitative assessment of CAIX expression of tumors may steer cancer treatment by predicting therapy respons...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00950

    authors: Huizing FJ,Hoeben BAW,Franssen GM,Boerman OC,Heskamp S,Bussink J

    更新日期:2019-02-04 00:00:00

  • Polyarginine molecular weight determines transfection efficiency of calcium condensed complexes.

    abstract::Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression but poses a risk of increased cytotoxicity and immunogenicity compared to low molec...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3007117

    authors: Alhakamy NA,Berkland CJ

    更新日期:2013-05-06 00:00:00

  • Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.

    abstract::The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH pept...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400248f

    authors: Flook AM,Yang J,Miao Y

    更新日期:2013-09-03 00:00:00

  • 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

  • Autophagy-related gene expression analysis of wild-type and atg5 gene knockout mouse embryonic fibroblast cells treated with polyethylenimine.

    abstract::The molecular mechanisms of autophagy in polyethylenimine (PEI)-treated cells are not well understood because of the use of nonspecific autophagy inhibitors. Here, we applied autophagy-related gene expression analysis to pinpoint the molecular mechanisms of autophagy in PEI-treated wild-type and atg5 gene knockout (at...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp500111u

    authors: Lin CW,Jan MS,Kuo JH

    更新日期:2014-09-02 00:00:00

  • Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases.

    abstract::In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to pe...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b01167

    authors: Wyatt EA,Davis ME

    更新日期:2020-02-03 00:00:00

  • Physicochemical characterization of molecular assemblies of miltefosine and amphotericin B.

    abstract::This study describes the interactions between two amphiphilic molecules with antileishmanial activity, amphotericin B (AmB) and miltefosine [hexadecylphosphocholine (HePC)], the latter being effective by the oral route. The effect of HePC on the aggregation state of AmB in aqueous solution and the interactions between...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp0601143

    authors: Ménez C,Legrand P,Rosilio V,Lesieur S,Barratt G

    更新日期:2007-03-01 00:00:00

  • Differential expression of the 18 kDa translocator protein (TSPO) by neoplastic and inflammatory cells in mouse tumors of breast cancer.

    abstract::Tumor-associated inflammation has been linked to angiogenesis, metastasis and poor prognosis. The 18 kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR), is expressed in activated immune cells such as macrophages, but also in a number of cancer cell lines such as those of breast...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp100433c

    authors: Zheng J,Boisgard R,Siquier-Pernet K,Decaudin D,Dollé F,Tavitian B

    更新日期:2011-06-06 00:00:00

  • MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells.

    abstract::Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO)...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp9001393

    authors: Guthi JS,Yang SG,Huang G,Li S,Khemtong C,Kessinger CW,Peyton M,Minna JD,Brown KC,Gao J

    更新日期:2010-02-01 00:00:00

  • Skin Delivery of Hydrophilic Biomacromolecules Using Marine Sponge Spicules.

    abstract::We report the development of sponge Haliclona sp. spicules, referred to as SHS, and its topical application in skin delivery of hydrophilic biomacromolecules, a series of fluorescein isothiocyanate-dextrans (FDs). SHS are silicious oxeas which are sharp-edged and rod-shaped (∼120 μm in length and ∼7 μm in diameter). S...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00468

    authors: Zhang S,Ou H,Liu C,Zhang Y,Mitragotri S,Wang D,Chen M

    更新日期:2017-09-05 00:00:00

  • pH-Responsive Nanophotosensitizer for an Enhanced Photodynamic Therapy of Colorectal Cancer Overexpressing EGFR.

    abstract::Photodynamic therapy (PDT) has been shown to kill cancer cells and improve survival and quality of life in cancer patients, and numerous new approaches have been considered for maximizing the efficacy of PDT. In this study, a new multifunctional nanophotosensitizer Ce6/GE11-(pH)micelle was developed to target epiderma...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00925

    authors: Chu WY,Tsai MH,Peng CL,Shih YH,Luo TY,Yang SJ,Shieh MJ

    更新日期:2018-04-02 00:00:00

  • Efficient Targeting Drug Delivery System for Lewis Lung Carcinoma, Leading to Histomorphological Abnormalities Restoration, Physiological and Psychological Statuses Improvement, and Metastasis Inhibition.

    abstract::Lung cancer is a kind of malignant tumor with high morbidity and metastasis tendency. Gambogic acid (GA) has demonstrated significant antitumor activity in vitro, but its poor water-solubility and adverse effects restrict its application in vivo and in clinic. In this study, a passive-targeting GA delivery system was ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00161

    authors: Yang Y,Cai H,Yuan X,Xu H,Hu Y,Rui X,Wu J,Chen J,Li J,Gao X,Yin D

    更新日期:2018-05-07 00:00:00

  • Role of prostaglandin pathway and alendronate-based carriers to enhance statin-induced bone.

    abstract::This study investigated the role of the prostaglandin (PG) pathway in locally applied, simvastatin-induced oral bone growth. The possibility of enhancing long-term bone augmentation with an alendronate-based carrier was initiated. Mandibles of 44 mature female rats were treated bilaterally with the following combinati...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp200045p

    authors: Lee Y,Liu X,Nawshad A,Marx DB,Wang D,Reinhardt RA

    更新日期:2011-08-01 00:00:00

  • Poloxamer-Decorated Polymer Nanoparticles for Lung Surfactant Compatibility.

    abstract::Lung-delivered polymer nanoparticles provoked dysfunction of the essential lung surfactant system. A steric shielding of the nanoparticle surface with poloxamers could minimize the unwanted interference of polymer nanoparticles with the biophysical function of lung surfactant. The extent of poly(styrene) and poly(lact...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00477

    authors: Beck-Broichsitter M,Bohr A,Ruge CA

    更新日期:2017-10-02 00:00:00

  • The effect of multiple N-methylation on intestinal permeability of cyclic hexapeptides.

    abstract::Recent progress in peptide synthesis simplified the synthesis of multiple N-methylation of peptides. To evaluate how multiple N-methylation affects the bioavailability of peptides, a poly alanine cyclic hexapeptide library (n = 54), varying in the number of N-methyl (N-Me) groups (1-5 groups) and their position, was s...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp1003306

    authors: Ovadia O,Greenberg S,Chatterjee J,Laufer B,Opperer F,Kessler H,Gilon C,Hoffman A

    更新日期:2011-04-04 00:00:00

  • Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer's Disease, Parkinson's Disease, and Intracerebral Hemorrhage.

    abstract::Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has als...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00474

    authors: Farr AC,Xiong MP

    更新日期:2021-02-01 00:00:00

  • Reduction Responsive Self-Assembled Nanoparticles Based on Disulfide-Linked Drug-Drug Conjugate with High Drug Loading and Antitumor Efficacy.

    abstract::Most anticancer drugs are poorly soluble and nonspecific, which restricts their clinical application. Drug conjugates, as a prodrug strategy, provide the possibility to overcome these shortcomings, especially combined with nanotechnology. Drug conjugate nanoparticles possess the advantages of high drug loading capacit...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00631

    authors: Song Q,Wang X,Wang Y,Liang Y,Zhou Y,Song X,He B,Zhang H,Dai W,Wang X,Zhang Q

    更新日期:2016-01-04 00:00:00

  • Cationic poly-L-lysine dendrimers: pharmacokinetics, biodistribution, and evidence for metabolism and bioresorption after intravenous administration to rats.

    abstract::Cationic poly-L-lysine 3H-dendrimers with either 16 or 32 surface amine groups (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation 3 and 4, respectively) have been synthesized and their pharmacokinetics and biodistribution investigated after intravenous administration to rats. The species...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp060032e

    authors: Boyd BJ,Kaminskas LM,Karellas P,Krippner G,Lessene R,Porter CJ

    更新日期:2006-09-01 00:00:00

  • Development of Liposomal Gemcitabine with High Drug Loading Capacity.

    abstract::Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and nonspecific side effects; however, it has been difficult to achieve liposomal Gem with high drug load...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b01284

    authors: Tamam H,Park J,Gadalla HH,Masters AR,Abdel-Aleem JA,Abdelrahman SI,Abdelrahman AA,Lyle LT,Yeo Y

    更新日期:2019-07-01 00:00:00