Design, synthesis and immunological evaluation of self-assembled antigenic peptides from dual-antigen targets: a broad-spectrum candidate for an effective antibreast cancer therapy

BackgroundConsidering the narrow immune response spectrum of a single epitope, and the nanoparticles (NPs) as a novel adjuvant can achieve efficient delivery of antigenic peptides safely, a nano-system (denoted as DSPE-PEG-Man@EM-NPs) based on cathepsin B-responsive antigenic peptides was designed and synthesized.MethodsHighly affinitive antigenic peptides were delivered by self-assembled NPs, and targeted erythrocyte membranes acted as a peptide carrier to improve antigenic peptides presentation and to strengthen cytotoxic T-cells reaction. Cathepsin B coupling could release antigenic peptides rapidly in dendritic cells.ResultsEvaluations showed that DSPE-PEG-Man@EM-NPs had obvious inhibitory effects towards both MCF-7 and MDA-MB-231 human breast cancer cell lines.ConclusionOverall, this strategy provides a novel strategy for boosting cytotoxic T lymphocytes response, thereby expanding the adaptation range of tumor antigenic peptides and improving the therapeutic effect of tumor immunotherapy with nanomedicine.

Download Full-text

Disulfide-induced self-assembled targets: A novel strategy for the label free colorimetric detection of DNAs/RNAs via unmodified gold nanoparticles

Scientific Reports ◽

10.1038/srep45837 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 10

Author(s):

Ehsan Shokri ◽

Morteza Hosseini ◽

Mehdi D. Davari ◽

Mohammad R. Ganjali ◽

Maikel P. Peppelenbosch ◽

...

Keyword(s):

Gold Nanoparticles ◽

Colorimetric Detection ◽

Label Free ◽

Self Assembled ◽

Novel Strategy

Download Full-text

Smart Self-Assembled Organic Nanoprobe for Protein-Specific Detection: Design, Synthesis, Application, and Mechanism Studies

Analytical Chemistry ◽

10.1021/acs.analchem.7b02923 ◽

2017 ◽

Vol 89 (18) ◽

pp. 10085-10093 ◽

Cited By ~ 23

Author(s):

Tang Gao ◽

Shuqi Yang ◽

Xiaozheng Cao ◽

Jie Dong ◽

Ning Zhao ◽

...

Keyword(s):

Specific Detection ◽

Design Synthesis ◽

Self Assembled

Download Full-text

Recent advances of melamine self-assembled graphitic carbon nitride-based materials: Design, synthesis and application in energy and environment

Chemical Engineering Journal ◽

10.1016/j.cej.2020.126951 ◽

2021 ◽

Vol 405 ◽

pp. 126951

Author(s):

Qinghua Liang ◽

Binbin Shao ◽

Shehua Tong ◽

Zhifeng Liu ◽

Lin Tang ◽

...

Keyword(s):

Carbon Nitride ◽

Materials Design ◽

Graphitic Carbon ◽

Graphitic Carbon Nitride ◽

Design Synthesis ◽

Energy And Environment ◽

Recent Advances ◽

Self Assembled

Download Full-text

SCIDOT-05. DEVELOPING VARIABLE LYMPHOCYTE RECEPTORS THAT TARGET PATHOLOGICALLY EXPOSED NEURAL ECM TO TREAT GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.1146 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi273-vi273

Author(s):

Benjamin J Umlauf ◽

Paul A Clark ◽

Jason M Lajoie ◽

Julia V Georgieva ◽

Samantha Bremner ◽

...

Keyword(s):

Ex Vivo ◽

Cytotoxic T Cells ◽

High Specificity ◽

Recognition System ◽

Therapeutic Benefit ◽

Immunogenic Peptide ◽

Immunogenic Peptides ◽

Novel Strategy ◽

Lymphocyte Receptors

Abstract INTRODUCTION The median survival of gliobastoma (GBM) patients remains less than two years despite aggressive treatments. Current targeted GBM therapies demonstrate initial therapeutic benefit; however, patients relapse due to therapeutic resistance and failure to eliminate GBM cells at the invasive margin. Therefore, we propose a two-prong approach: first, target pathologic disruption of the blood brain barrier (BBB) via exposure of neural ECM rather than disease markers to overcome therapy-resistant GBM; and second, designing therapeutic payloads that extracellularly spread throughout the tumor volume. METHODS Variable Lymphocyte Receptors (VLRs, a lamprey-derived antigen recognition system) were identified with high specificity for neural ECM. Candidate VLRs underwent further refinement using ex vivo tissue staining. Utilizing pathologic disruption of BBB as an approach for targeting GBM was confirmed in vivo with intracranial murine glioblastoma models. Finally, an immunogenic peptide was attached via a cleavable linker to the neural ECM binding VLRs for conditional release extracellularly to spread throughout the tumor. RESULTS The lead neural ECM-binding VLR candidate, named P1C10, demonstrates diffuse binding to parenchymal neural ECM, without detectable binding to other tissues. P1C10 demonstrates nanomolar affinity for neural ECM, and preferentially accumulates in intracranial GL261 and U87 murine GBM models. Finally, P1C10-targeted doxorubicin-loaded liposomes significant increased survival of mice with intracranial GBM. In additional studies, treating murine GBM models with a P1C10 VLR linked to an immunogenic peptide reduced GBM proliferation and increased infiltration of cytotoxic T cells. CONCLUSIONS We present proof-of-concept demonstration for targeting intracranial GBM via neural ECM exposed at pathological BBB disrupted sites. Additionally, P1C10 neural ECM-targeting VLR delivers chemotherapy-loaded nanoparticles and immunogenic peptides designed to spread extracellularly throughout the tumor. Thus, this novel strategy links a physiological ECM targeting scheme with extracellular-released therapeutics to treat primary GBM, and has potential for delivering therapies to other CNS diseases with pathological BBB.

Download Full-text

Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling

Antioxidants ◽

10.3390/antiox9060519 ◽

2020 ◽

Vol 9 (6) ◽

pp. 519 ◽

Cited By ~ 1

Author(s):

Ahmed Dhahir Latif ◽

Tamás Jernei ◽

Ana Podolski-Renić ◽

Ching-Ying Kuo ◽

Máté Vágvölgyi ◽

...

Keyword(s):

Breast Cancer ◽

Mitochondrial Membrane ◽

Redox Balance ◽

Breast Cancer Cell Lines ◽

Antitumor Action ◽

Hybrid Compounds ◽

Mitochondrial Membrane Depolarization ◽

Ic50 Values ◽

Novel Strategy

Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC50 values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou–Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.

Download Full-text

Unchain My Blood: Lessons Learned from Self-Assembled Dendrimers as Nanoscale Heparin Binders

Biomolecules ◽

10.3390/biom9080385 ◽

2019 ◽

Vol 9 (8) ◽

pp. 385 ◽

Cited By ~ 1

Author(s):

Domenico Marson ◽

Erik Laurini ◽

Suzana Aulic ◽

Maurizio Fermeglia ◽

Sabrina Pricl

Keyword(s):

Biomedical Applications ◽

Anticoagulant Activity ◽

Lessons Learned ◽

Clinical Settings ◽

Computational Results ◽

Heparin Binding ◽

Design Synthesis ◽

Self Assembled ◽

Hybrid Methodology

This review work reports a collection of coupled experimental/computational results taken from our own experience in the field of self-assembled dendrimers for heparin binding. These studies present and discuss both the potentiality played by this hybrid methodology to the design, synthesis, and development of possible protamine replacers for heparin anticoagulant activity reversal in biomedical applications, and the obstacles this field has still to overcome before these molecules can be translated into nanomedicines available in clinical settings.

Download Full-text