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Start Over Descriptor "Chemical conjugation" Journal biomaterials
4 results on '"Chemical conjugation"'

1. The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants.

Author

Liang, Zhihui, Bao, Hang, Yao, Zhiying, Li, Min, Chen, Chen, Zhang, Lei, Wang, Huiyang, Guo, Yiyang, Ma, Yubin, Yang, Xuecheng, Yu, Ge, Zhang, Jiancheng, Xue, Changying, Sun, Bingbing, and Mao, Chuanbin

Subjects
*T cells, *HEPATITIS associated antigen, *CYTOTOXIC T cells, *B cell differentiation, *T cell differentiation, *CPG nucleotides, *B cell receptors
Abstract

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5′ or 3′ end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3′-end exposure, the 5′-end exposure of CpG in combination adjuvants (Al-CpG-5′) enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5′ enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5′ allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting T fh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines. A combination adjuvant system is constructed by covalently conjugating engineered aluminum oxyhydroxide nanoparticles with different ends of CpG, in order to investigate their immunostimulatory effects. The results demonstrate that the combination adjuvants, with the 5′ end of CpG exposed, induce enhanced and balanced immune responses in both SARS-CoV-2 RBD and HBV vaccines. This finding provides insight for a more rational design of nanomaterial-based adjuvants for prophylactic and therapeutic vaccines. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2024
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2. Bioreducible polymer-conjugated oncolytic adenovirus for hepatoma-specific therapy via systemic administration

Author

Kim, Pyung-Hwan, Kim, Jaesung, Kim, Tae-il, Nam, Hye Yeong, Yockman, James W., Kim, Minjung, Kim, Sung Wan, and Yun, Chae-Ok

Subjects
*CONJUGATED polymers, *HEPATOCELLULAR carcinoma, *BIOCONJUGATES, *ADENOVIRUSES, *ARGININE, *BIOMEDICAL materials, *HEPATOTOXICOLOGY, *CANCER cells, *THERAPEUTICS
Abstract

Abstract: Systemic administration of adenovirus (Ad) vectors is complicated by host immune responses and viral accumulation in the liver, resulting in a short circulatory virus half-life, low efficacy, and host side effects. Ad surface modification is thus required to enhance safety and therapeutic efficacy. An arginine-grafted bioreducible polymer (ABP) was chemically conjugated to the Ad surface, generating Ad-ΔE1/GFP-ABP. A hepatocellular carcinoma [HCC]-selective oncolytic Ad complex, YKL-1001-ABP, was also generated. Transduction efficiency of Ad-ΔE1/GFP-ABP was enhanced compared to naked Ad-ΔE1/GFP. YKL-1001-ABP elicited an enhanced and specific killing effect in liver cancer cells (Huh7 and HepG2) expressing α-fetoprotein (AFP). Compared with naked Ad, systemic administration of ABP-conjugated Ad resulted in reduced liver toxicity and interleukin (IL)-6 production in vitro and in vivo. Ad-ΔE1/GFP-ABP was more resistant to the neutralizing effects of human serum compared to naked Ad-ΔE1/GFP. ABP conjugation extended blood circulation time 45-fold and reduced anti-Ad Ab neutralization. Moreover, systemic administration of YKL-1001-ABP markedly suppressed growth of Huh7 hepatocellular carcinoma. These results demonstrate that chemical conjugation of ABP to the Ad surface improves safety and efficacy, indicating that ABP-conjugated Ad is a potentially useful cancer therapeutic agent to target cancer via systemic administration. [Copyright &y& Elsevier]

Published
2011
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3. A multifunctional heptamethine near-infrared dye for cancer theranosis

Author

Hu Zheng, Lilong Zhang, Yu-Feng Liang, Xinze Ran, Chunmeng Shi, Shenglin Luo, Tianmin Cheng, Yongping Su, Xu Tan, Qingrong Qi, Lingling Weng, Qinyuan Guo, and Erlong Zhang

Subjects
Diagnostic Imaging, Male, Materials science, Indoles, Tumor inhibition, Biophysics, Contrast Media, Mice, Nude, Bioengineering, Nanotechnology, Antineoplastic Agents, Cancer targeting, Biomaterials, Rats, Sprague-Dawley, Broad spectrum, Mice, Neoplasms, medicine, Animals, Humans, Tumor xenograft, Cells, Cultured, Fluorescent Dyes, Cancer, Chemical conjugation, Carbocyanines, medicine.disease, Xenograft Model Antitumor Assays, Rats, Mice, Inbred C57BL, Mechanics of Materials, Personalized oncology, Ceramics and Composites, Molecular imaging, HeLa Cells
Abstract

Personalized oncology significantly relies on the development of cancer theranostic agents to integrate cancer therapeutics and diagnostics. Current most common strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer targeted ligands, contrast agents and therapeutic agents. Here we report the chemical synthesis and biological characterization of a new heptamethine dye, termed as IR-808DB, natively with multifunctional characteristics of cancer targeting, near-infrared fluorescence imaging, and efficient anticancer activity. The tumor inhibition effect of IR-808DB is higher than that of cyclophosphamide (CTX) toward a broad spectrum of tumor xenograft models. These findings provide IR-808DB a promising prospect as a new cancer theranostic agent that would enable integration of cancer targeted therapeutics and diagnostics without requirement of multi-component chemical conjugation.

Published
2012

4. A review of NIR dyes in cancer targeting and imaging

Author

Shenglin Luo, Erlong Zhang, Tianmin Cheng, Yongping Su, and Chunmeng Shi

Subjects
Diagnostic Imaging, Tumor targeting, Fluorescence-lifetime imaging microscopy, Materials science, Biophysics, Bioengineering, Nanotechnology, Cancer targeting, Sensitivity and Specificity, Biomaterials, Neoplasms, Medical imaging, Animals, Humans, Fluorescent Dyes, Spectroscopy, Near-Infrared, Molecular Structure, Near-infrared spectroscopy, technology, industry, and agriculture, Chemical conjugation, equipment and supplies, Small molecule, Molecular Imaging, Mechanics of Materials, Ceramics and Composites, Nanoparticles, Molecular imaging, Biomedical engineering
Abstract

The development of multifunctional agents for simultaneous tumor targeting and near infrared (NIR) fluorescence imaging is expected to have significant impact on future personalized oncology owing to the very low tissue autofluorescence and high tissue penetration depth in the NIR spectrum window. Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. Organic dyes have shown promising clinical implications as non-targeting agents for optical imaging in which indocyanine green has long been implemented in clinical use. Recently, significant progress has been made on the development of unique NIR dyes with tumor targeting properties. Current ongoing design strategies have overcome some of the limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. This potential is further realized with the use of these NIR dyes or NIR dye-encapsulated nanoparticles by conjugation with tumor specific ligands (such as small molecules, peptides, proteins and antibodies) for tumor targeted imaging. Very recently, natively multifunctional NIR dyes that can preferentially accumulate in tumor cells without the need of chemical conjugation to tumor targeting ligands have been developed and these dyes have shown unique optical and pharmaceutical properties for biomedical imaging with superior signal-to-background contrast index. The main focus of this article is to provide a concise overview of newly developed NIR dyes and their potential applications in cancer targeting and imaging. The development of future multifunctional agents by combining targeting, imaging and even therapeutic routes will also be discussed. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer.

Published
2011

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