Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development

Download

index.pdf

Date

2017-02-10

Author

Bayyurt, Banu
Tincer, Gizem
Almacioglu, Kubra
Alpdundar, Esin
Gürsel, Mayda
GÜRSEL, İHSAN

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

269
views

0
downloads

Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine.

Subject Keywords

Pharmaceutical Science

URI

https://hdl.handle.net/11511/43004

Journal

JOURNAL OF CONTROLLED RELEASE

DOI

https://doi.org/10.1016/j.jconrel.2017.01.004

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Dual-adjuvant effect of pH-sensitive liposomes loaded with STING and TLR9 agonists regress tumor development by enhancing Th1 immune response Kocabas, Banu Bayyurt; Almacioglu, Kubra; Bulut, Esin Alpdundar; Gucluler, Gozde; Tincer, Gizem; Bayik, Defne; Gürsel, Mayda; GÜRSEL, İHSAN (Elsevier BV, 2020-12-01) Nucleic acid-based pattern recognition receptor agonists are effective adjuvants and immunotherapeutic agents. Rather than single applications, ligand combinations could synergistically potentiate immune responses by elevating cytokine and chemokine production via triggering multiple signaling pathways. However, short half-lives of such labile ligands due to nuclease attack and limited cellular uptake due to their structure significantly hamper their in vivo performances. More importantly, simultaneous deli...
Concentration-dependent differing actions of the nonsteroidal anti-inflammatory drug, celecoxib, in distearoyl phosphatidylcholine multilamellar vesicles Sade, Asli; Banerjee, Sreeparna; Severcan, Feride (Informa UK Limited, 2010-06-01) The interactions of the nonsteroidal anti-inflammatory drug, celecoxib, with 1,2-distearoyl-sn-glycero-3-phosphocholine multilamellar vesicles were studied as a function of temperature and different drug concentrations, using Fourier transform infrared spectroscopy, differential scanning calorimetry, and turbidity technique at 440 nm. Our studies reveal that celecoxib lowers the main phase-transition temperature and decreases the fluidity of the membranes at all concentrations. Celecoxib induced opposing ef...
SYNTHESIS AND ANTIFUNGAL ACTIVITY OF SOME NEW BENZIMIDAZOLE DERIVATIVES GOKER, H; ERTAN, R; AKGUN, H; YULUG, N (Wiley, 1991-05-01) Synthesis and antifungal evaluation of 5-ethoxycarbonyl-2-(substituted-benzyl or phenoxymethyl)benzimidazoles are reported. Structures of the compounds were elucidated with IR-, H-1-NMR-, C-13-NMR-, mass-spectra and elemental analysis. Preliminary results show that none of the synthesized benzimidazole derivatives has antifungal activity at the concentration of 100-mu-g/ml against Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis.
Differential response to doxorubicin in breast cancer subtypes simulated by a microfluidic tumor model Özçelikkale, Altuğ; Noe-Kim, Victoria; Elzey, Bennett D.; Dong, Zizheng; Zhang, Jian-Ting; Kim, Kwangmeyung; Kwon, Ick Chan; Park, Kinam; Han, Bumsoo (Elsevier BV, 2017-11-01) Successful drug delivery and overcoming drug resistance are the primary clinical challenges for management and treatment of cancer. The ability to rapidly screen drugs and delivery systems within physiologically relevant environments is critically important; yet is currently limited due to lack of appropriate tumor models. To address this problem, we developed the Tumor-microenvironment-on-chip (T-MOC), a new microfluidic tumor model simulating the interstitial flow, plasma clearance, and transport of the d...
Prospective evaluation of Vitamin K2, Raloxifene and their co-administration in osteoporotic rats Tasci, A. G.; BİLGİLİ, HASAN; Altunay, H.; Gecit, M. R.; Keskin, Dilek (Elsevier BV, 2011-07-17) In this study, therapeutic effects of Vitamin K2, Raloxifene and their co-administration on bone, uterus, blood and weight profiles were investigated with an ovariectomized rat model. Forty Wistar rats were divided into five groups (n = 8): Raloxifene (R), Vitamin K2 (K), Raloxifene + Vitamin K2 (R + K), ovariectomized controls (OVX) and Sham-operated controls (Sham). Treatment began 3 months after ovariectomy. Vitamin K2 and Raloxifene were administered 30 and 1.5 mg/kg/day separately and in combination fi...

Citation Formats

B. Bayyurt, G. Tincer, K. Almacioglu, E. Alpdundar, M. Gürsel, and İ. GÜRSEL, “Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development,” JOURNAL OF CONTROLLED RELEASE, pp. 134–144, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/43004.