Antibody nanocarriers for cancer management

Dang, Megan N.; Hoover, Elise C.; Scully, Mackenzie A.; Sterin, Eric H.; Day, Emily S.

doi:10.1016/j.cobme.2021.100295

Cited by 3 publications

(2 citation statements)

References 62 publications

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“…Here, we implemented antibody targeting of EC-expressed E-selectin using antibody-functionalized NPs. Compared to free antibodies, antibody–NP conjugates exhibit multivalent binding to targeted receptors, which increases avidity and efficacy, , and are therefore used in this study.…”

Section: Discussionmentioning

confidence: 99%

“…This includes the length of the linker used to attach the antibodies (which influences antibody accessibility and flexibility) as well as the density and directionality of the antibodies on the NP surface. Antibodies are typically conjugated to the surface of gold NPs using heterobifunctional poly(ethylene glycol) (PEG) linkers that contain a thiol or disulfide group at one end (to facilitate attachment to gold) and an N -hydroxysuccinimide (NHS), succinimidyl valerate (SVA), or a similar group at the other end (to facilitate binding to free amines present on antibodies) . While effective, this method results in non-directional antibody orientation, meaning that the antigen-binding region (Fab) of the antibody may face outward from the NP as desired, or it may face inward, rendering it less effective.…”

Section: Introductionmentioning

confidence: 99%

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E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells

Fereshteh

Dang

Wenck

et al. 2023

ACS Appl. Nano Mater.

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Extravasation of circulating tumor cells (CTCs) from the vasculature is a key step in cancer metastasis. CTCs bind to cell adhesion molecules (CAMs) expressed by endothelial cells (ECs) for flow arrest prior to extravasation. While a number of EC-expressed CAMs have been implicated in facilitating CTC binding, this work investigated the efficacy of inhibiting cancer cell binding to human lung microvascular ECs via antibody blocking of E-selectin using antibody-functionalized gold nanoshells (NS). The antibody-functionalized gold NS were synthesized using both directional and non-directional antibody conjugation techniques with variations in synthesis parameters (linker length, amount of passivating agents, and ratio of antibodies to NS) to gain a better understanding of these properties on the resultant hydrodynamic diameter, zeta potential, and antibody loading density. We quantified the ability of E-selectin antibody-functionalized NS to bind human lung microvascular endothelial cells (HMVEC-Ls) under non-inflamed and inflamed (TNF-α) conditions to inhibit binding of triple-negative MDA-MB-231s. E-selectin-targeted NS prepared using non-directional conjugation had higher antibody loading than those prepared via directional conjugation, resulting in the conjugates having similar overall binding to HMVEC-Ls at a given antibody concentration. E-selectin-targeted NS reduced MDA-MB-231 binding to HMVEC-Ls by up to 41% as determined using an in vitro binding assay. These results provide useful insights into the characteristics of antibody-functionalized NS prepared under different conditions while also demonstrating proof of concept that these conjugates hold potential to inhibit CTC binding to ECs, a critical step in extravasation during metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells

Fereshteh

Dang

Wenck

et al. 2023

ACS Appl. Nano Mater.

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Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide–Thiol Chemistry

Hoover,

Roy Chowdhury,

Ruggiero

et al. 2024

ACS Omega

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Polymeric nanoparticles (NPs) have shown great promise as highly modifiable platforms that can be applied across many different disease states. They are advantageous because they can encapsulate a range of hydrophobic and hydrophilic cargoes while having customizable surface properties. Depending on the desired biointerfacing capabilities, the surface of polymeric NPs can be modified with moieties, such as antibodies, peptides, nucleic acids, and more. The work presented here is intended to provide mechanistic insight into how different parameters influence the loading of antibodies, small interfering ribonucleic acids (siRNAs), or both on the surface of poly(lactic-co-glycolic acid) (PLGA) NPs via maleimide− thiol chemistry. Some of the conjugation parameters investigated include the buffer concentration, maleimide to protein ratio, and the addition of an excipient such as Tween-20. Through variation in the concentration of FZD7 antibodies added to the reaction mixture, we established tunable conjugation and found the upper limit of their loading density under the conditions tested. We also confirmed antibody conjugation through two different mechanisms: via a thiol-modified antibody or a thiol-modified poly(ethylene glycol) (PEG) linker. Conjugation of thiolated siRNA duplexes targeting β-catenin was also investigated through variations in both Tween-20 concentration and CaCl 2 buffer concentration. Finally, the coconjugation of both antibodies and siRNA duplexes was explored. Overall, this work outlines a basis for tunable biomolecule loading on polymer NPs using maleimide−thiol chemistry and reveals the incredible versatility of polymer NP platforms.

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Nanotaşiyicilarin Kanser Hücreleri̇ne Akti̇f Ve Pasi̇f Olarak Hedeflenmesi̇nde Kullanilan Yöntemler

Alkaç,

Keskin,

Çerçi

2024

Kocatepe Tıp Dergisi

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Nanoteknolojideki gelişmelerle beraber her geçen gün artan kullanım alanı ve kolaylığı ile nanomalzeme temelli ilaç taşıma sistemleri; ilaç moleküllerinin tümör dokusuna hedeflenmesi, tümör hücresindeki çoklu ilaç direncinin kırılması ve doza bağlı azalmış teröpatik etkinin iyileştirilmesinde potansiyel güçlü özelliklere sahiptir. Son yıllarda, birçok kanser türünü hedefleyen antikanser tedavi stratejilerinde, nanoteknolojiye dayalı yeni metotlar ve yaklaşımların geliştirilmesiyle nanomalzemelere karşı ilgi artmaktadır. Nanoteknolojideki gelişmelerin hızlı bir şekilde ilerlemesiyle birlikte nanomalzemelerin kanser terapötiklerine entegrasyonu ve kanser hücrelerinin yüzeylerinde bulunan belirteçlere spesifik hedeflenmesi kanser tedavisinde devrim niteliğinde iyileşmeler sağlamıştır. Nano taşıyıcı sistemlerinde ilaç yüklemesi sayesinde vücutta artan ilaç yüklenmesi nedeniyle oluşan toksisitenin azalmasını sağlayan iyileştirilmiş ilaç yarı ömür, kontrollü ve seçici ilaç salınımı için bileşenlerin boyutları, morfolojileri ve yüzey kimyaları çeşitli yöntemlerle değiştirilerek ilaç taşıma sistemleri yeniden tasarlanabilmektedir. Böylece özel yapım nanomateryaller, kanser hücrelerini öngörülebilir bir şekilde hedefleyerek yüklü ilaçları etkili bir şekilde kanser hücresine iletebilir. Şimdiye kadar, kanser tedavisinde nano ölçekli boyutları ve çok yönlü fizikokimyasal özellikleri nedeniyle geleneksel formülasyonlara göre hazırlanmış daha üstün farmakokinetik ve farmakodinamik profillere sahip akıllı ilaç salınım sistemlerinde kullanılması için polimerik nanomateryaller, metalik nanopartiküller, karbon bazlı materyaller, lipozomlar ve dendrimerler üretilmiştir. Bu derlemede, ilaç taşıma sistemlerinin oluşturulmasında temel olarak kullanılan nanopartiküller, miseller, karbon nanotüpler, dendrimerler, kuantum noktaları ve lipozomlar dahil olmak üzere çeşitli ilaç salınım sistemlerinin fizikokimyasal, farmakokinetik ve farmakodinamik özelliklerinin avantajları ve dezavantajlarının ortaya konması amaçlanmıştır. Bunun yanı sıra pasif ve aktif taşıma olmak üzere iki farklı ilaç taşıma yönteminin kanser tedavisindeki uygulama alanları tartışılarak nanotaşıyıcı sistemlerin gelecekteki klinik çalışmalarda kullanımları açısından konuyla ilgilenenler için bir perspektif oluşturmaktadır.

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Antibody nanocarriers for cancer management

Cited by 3 publications

References 62 publications

E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells

E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells

Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide–Thiol Chemistry

Nanotaşiyicilarin Kanser Hücreleri̇ne Akti̇f Ve Pasi̇f Olarak Hedeflenmesi̇nde Kullanilan Yöntemler

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