Spacer length and serum protein adsorption affect active targeting of trastuzumab-modified nanoparticles

Barth, Christina; Spreen, Hendrik; Mulac, Dennis; Keuter, Lucas; Behrens, Matthias; Humpf, Hans‐Ulrich; Langer, Klaus

doi:10.1016/j.bbiosy.2021.100032

Cited by 5 publications

(2 citation statements)

References 52 publications

(81 reference statements)

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“…60 As protein coronas may not only alter NP circulation time but also mask targeting moieties, a number of strategies preventing corona formation have been developed. [61][62][63][64] These include PEGylation, coating NP with other polymers (e.g., zwitterionic polymers), and careful NP design. [65][66][67] A fascinating alternative to polymeric NPs for improving circulation kinetic and biodistribution is the use of biological membranes that can completely shield the particles and protect them from protein corona formation and macrophage clearance.…”

Section: Protein Corona Formationmentioning

confidence: 99%

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

Kachanov,

Kostyusheva,

Brezgin

et al. 2024

Medicinal Research Reviews

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Over the past decade, in vivo gene replacement therapy has significantly advanced, resulting in market approval of numerous therapeutics predominantly relying on adeno‐associated viral vectors (AAV). While viral vectors have undeniably addressed several critical healthcare challenges, their clinical application has unveiled a range of limitations and safety concerns. This review highlights the emerging challenges in the field of gene therapy. At first, we discuss both the role of biological barriers in viral gene therapy with a focus on AAVs, and review current landscape of in vivo human gene therapy. We delineate advantages and disadvantages of AAVs as gene delivery vehicles, mostly from the safety perspective (hepatotoxicity, cardiotoxicity, neurotoxicity, inflammatory responses etc.), and outline the mechanisms of adverse events in response to AAV. Contribution of every aspect of AAV vectors (genomic structure, capsid proteins) and host responses to injected AAV is considered and substantiated by basic, translational and clinical studies. The updated evaluation of recent AAV clinical trials and current medical experience clearly shows the risks of AAVs that sometimes overshadow the hopes for curing a hereditary disease. At last, a set of established and new molecular and nanotechnology tools and approaches are provided as potential solutions for mitigating or eliminating side effects. The increasing number of severe adverse reactions and, sadly deaths, demands decisive actions to resolve the issue of immune responses and extremely high doses of viral vectors used for gene therapy. In response to these challenges, various strategies are under development, including approaches aimed at augmenting characteristics of viral vectors and others focused on creating secure and efficacious non‐viral vectors. This comprehensive review offers an overarching perspective on the present state of gene therapy utilizing both viral and non‐viral vectors.

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Section: Protein Corona Formationmentioning

confidence: 99%

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

Kachanov,

Kostyusheva,

Brezgin

et al. 2024

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…To mitigate the influence of steric hindrance, it is common to use spacers of different lengths to try and optimize the orientation of the imaging label with regard to the pharmacophore. This strategy has been successfully explored for i.e., for the gastrin releasing peptide receptor (GRPR [53,54]), PSMA [47,[55][56][57], human epidermal growth factor 2 (HER2 [58]) and the folate receptor α [59]. Alternatively, the spacer can be used to promote complementary interactions within the binding pocket, essentially making it an integral part of the pharmacophore.…”

Section: Plasma Protein Bindingmentioning

confidence: 99%

Lessons learned in application driven imaging agent design for image-guided surgery

Buckle,

Rietbergen,

de Wit -van der Veen

et al. 2024

Eur J Nucl Med Mol Imaging

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To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent’s pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.

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Trastuzumab for Active Targeting in Cancer Therapy

Marques,

da Costa,

Velho

et al. 2023

Handbook of Cancer and Immunology

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Spacer length and serum protein adsorption affect active targeting of trastuzumab-modified nanoparticles

Cited by 5 publications

References 52 publications

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

Lessons learned in application driven imaging agent design for image-guided surgery

Trastuzumab for Active Targeting in Cancer Therapy

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