Electrostatic interaction of tumor-targeting adenoviruses with aminoclay acquires enhanced infectivity to tumor cells inside the bladder and has better cytotoxic activity

Kim, Soo-Yeon; Kwon, Whi‐An; Shin, Seung-Phil; Seo, Ho Kyung; Lim, Soo-Jeong; Jung, Yuh‐Seog; Han, Hyo-Kyung; Jeong, Kyung‐Chae; Lee, Sang-Jin

doi:10.1080/10717544.2017.1413450

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…In HIT, the electrostatic interactions between positively charged PF4 and negatively charged heparin drive the formation of the PF4-heparin complex [33]. The surface of adenoviruses is negatively charged [34]; therefore, one could postulate that PF4 released from platelets can potentially form an immunogenic complex with adenoviral particles, further bound by IgG antibodies. Such a multimolecular complex could subsequently bind to platelets through the Fc receptor, activating thrombocytes and causing an additional release of PF4, leading to VITT.…”

Section: Generation Of Antibodies Against Platelet Factormentioning

confidence: 99%

Thrombotic Thrombocytopenia after COVID-19 Vaccination: In Search of the Underlying Mechanism

2021

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The rollout of COVID-19 vaccines brings hope for successful pandemic mitigation and getting the transmission of SARS-CoV-2 under control. The vaccines authorized in Europe displayed a good safety profile in the clinical trials. However, during their post-authorization use, unusual thrombotic events associated with thrombocytopenia have rarely been reported for vector vaccines. This led to the temporary suspension of the AZD1222 vaccine (Oxford/AstraZeneca) in various European countries and the Ad26.COV2 vaccine (Janssen/Johnson&Johnson) in the United States, with regulatory bodies launching investigations into potential causal associations. The thromboembolic reactions were also rarely reported after mRNA vaccines. The exact cause of these adverse effects remains to be elucidated. The present paper outlines the hypotheses on the mechanisms behind the very rare thrombotic thrombocytopenia reported after the COVID-19 vaccination, along with currently existing evidence and future research prospects. The following are discussed: (i) the role of antibodies against platelet factor 4 (PF4), (ii) the direct interaction between adenoviral vector and platelets, (iii) the cross-reactivity of antibodies against SARS-CoV-2 spike protein with PF4, (iv) cross-reactivity of anti-adenovirus antibodies and PF4, (v) interaction between spike protein and platelets, (vi) the platelet expression of spike protein and subsequent immune response, and (vii) the platelet expression of other adenoviral proteins and subsequent reactions. It is also plausible that thrombotic thrombocytopenia after the COVID-19 vaccine is multifactorial. The elucidation of the causes of these adverse events is pivotal in taking precautionary measures and managing vaccine hesitancy. It needs to be stressed, however, that the reported cases are currently sporadic and that the benefits of COVID-19 vaccines vastly outweigh their potential risks.

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Section: Generation Of Antibodies Against Platelet Factormentioning

confidence: 99%

Thrombotic Thrombocytopenia after COVID-19 Vaccination: In Search of the Underlying Mechanism

2021

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“…The drug-clay complexes can regulate drug release properties by interacting with negatively charged drug molecules in water. Indeed, various delivery systems have been developed using Eudragit-coated liposome or aminoclay as efficient and versatile biocompatible carriers [33,34]. The charges of AC-L are made positive by the amino groups (-NH 3 ) of aminoclay and the charges of the anionic polymer nanoparticles of EAC-L are negative because of the carbonyl groups on the polymeric chain extremities.…”

Section: Discussionmentioning

confidence: 99%

Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model

Kim

Park

et al. 2020

J Nanobiotechnol

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Background Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. Results All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17). Conclusion We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

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“…The drug-clay complexes can regulate drug release properties by interacting with negatively charged drug molecules in water. Indeed, various delivery systems have been developed using Eudragit-coated liposome or aminoclay as e cient and versatile biocompatible carriers [30,31]. The charges of AC-L are made positive by the amino groups (-NH 3 ) of aminoclay and the charges of the anionic polymer nanoparticles of EAC-L are negative because of the carbonyl groups on the polymeric chain extremities.…”

Section: Discussionmentioning

confidence: 99%

Nanocomposites-Based Targeted Oral Drug Delivery Systems with Infliximab in a Murine Colitis Model

Kim

Park

et al. 2020

Preprint

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Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. We developed a colon-specific drug delivery system for the oral administration of IFX using ternary nanocomposite carriers. Nanocomposite carriers consisting of liposomes, aminoclay-coated liposomes (AC-L), Eudragit S100 AC-L (EAC-L) or those carrying IFX (IFX-L, AC-IFX-L, and EAC-IFX-L) were orally administered to mice with dextran sulfate sodium-induced colitis. We evaluated the effects of nanocomposite carriers on lymphocytes and monocytes in peripheral blood mononuclear cells (PBMC) of IBD patients. We studied the therapeutic effects of the nanocomposites themselves and nanocomposites with IFX at target sites in vivo and in vitro . All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions ( Tnfa , Il1b , and Il17 ). We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.

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Electrostatic interaction of tumor-targeting adenoviruses with aminoclay acquires enhanced infectivity to tumor cells inside the bladder and has better cytotoxic activity

Cited by 14 publications

References 26 publications

Thrombotic Thrombocytopenia after COVID-19 Vaccination: In Search of the Underlying Mechanism

Thrombotic Thrombocytopenia after COVID-19 Vaccination: In Search of the Underlying Mechanism

Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model

Nanocomposites-Based Targeted Oral Drug Delivery Systems with Infliximab in a Murine Colitis Model

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