Antibody Targeting of Nanoparticles to Tumor-Specific Receptors: Immunoliposomes

Rothdiener, Miriam; Beuttler, Julia; Messerschmidt, Sylvia K.E.; Kontermann, Roland E.

doi:10.1007/978-1-60761-609-2_20

Cited by 26 publications

(17 citation statements)

References 9 publications

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“…For example, co-delivery of Cum and Paclitaxel would be of great significance in future in that the synergistic antitumor effect of Cum and Paclitaxel has been already demonstrated in previous studies (Ganta et al, 2009;Hossain et al, 2012). Moreover, increasing the targeting ability of Cum-NPs by receptor-targeting peptides remains to be the most attractive research focus (Rothdiener et al, 2010;Franzen et al, 2011;Guo et al, 2011). It is hypothesized that a combination of passive targeting, with receptor targeting peptides, may significantly amplify the antitumor activity of the drug delivery system (Yu et al, 2010;Cutler et al, 2013;Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

Yin¹,

Zhang²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

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Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

Yin¹,

Zhang²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…34,37,41,42 Briefly, all lipids were mixed in a round bottom flask and dissolved in chloroform:methanol (9:1 v/v). A thin and uniform lipid film was obtained by evaporating the solvents under pressure for 30 minutes at 42°C.…”

Section: 40mentioning

confidence: 99%

“…36, 37 Fresh, preformed liposomes were incubated with prereduced scFv. ScFvs were reduced using TCEP (10 mM at a final concentration) 34,37 under N 2 at room temperature for 1 hour prior to the coupling.…”

Section: Immunoliposome Formulation and Characterizationmentioning

confidence: 99%

“…ScFvs were reduced using TCEP (10 mM at a final concentration) 34,37 under N 2 at room temperature for 1 hour prior to the coupling. We found that reduction of scFv was a necessary step, as we observed greatly reduced binding without reduction, although the majority of scFv was present as monomer (data not shown).…”

Section: Immunoliposome Formulation and Characterizationmentioning

confidence: 99%

“…Cultures were pelleted at 4,500× g for 10 minutes at 4°C and frozen until further use. Pellets were thawed and resuspended in ice-cold periplasmic preparation buffer (30 mM tris-HCl, 20% sucrose, and 1 mM EDTA 36, 37 The cells were lysed with 50 µg/mL lysozyme, 37 and the spheroblasts were stabilized with 5 mM MgSO 4 . Samples were centrifuged at 10,000× g for 15 minutes at 4°C, and supernatants were collected, respun, and passed over 0.45 µm filters.…”

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confidence: 99%

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Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Saeed

Brakel

Zalba

et al. 2016

IJN

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Therapy of melanoma using T-cells with genetically introduced T-cell receptors (TCRs) directed against a tumor-selective cancer testis antigen (CTA) NY-ESO1 demonstrated clear antitumor responses in patients without side effects. Here, we exploited the concept of TCR-mediated targeting through introduction of single-chain variable fragment (scFv) antibodies that mimic TCRs in binding major histocompatibility complex-restricted CTA. We produced scFv antibodies directed against Melanoma AntiGEn A1 (MAGE A1) presented by human leukocyte antigen A1 (HLA-A1), in short M1/A1, and coupled these TCR-like antibodies to liposomes to achieve specific melanoma targeting. Two anti-M1/A1 antibodies with different ligand-binding affinities were derived from a phage-display library and reformatted into scFvs with an added cysteine at their carboxyl termini. Protein production conditions, ie, bacterial strain, temperature, time, and compartments, were optimized, and following production, scFv proteins were purified by immobilized metal ion affinity chromatography. Batches of pure scFvs were validated for specific binding to M1/A1-positive B-cells by flow cytometry. Coupling of scFvs to liposomes was conducted by employing different conditions, and an optimized procedure was achieved. In vitro experiments with immunoliposomes demonstrated binding of M1/A1-positive B-cells as well as M1/A1-positive melanoma cells and internalization by these cells using flow cytometry and confocal microscopy. Notably, the scFv with nonenhanced affinity of M1/A1, but not the one with enhanced affinity, was exclusively bound to and internalized by melanoma tumor cells expressing M1/A1. Taken together, antigen-mediated targeting of tumor cells as well as promoting internalization of nanoparticles by these tumor cells is mediated by TCR-like scFv and can contribute to melanoma-specific targeting.

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Immunoliposomes for Specific Drug Delivery

Calin¹

2012

Antibody‐Mediated Drug Delivery Systems

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Antibody Targeting of Nanoparticles to Tumor-Specific Receptors: Immunoliposomes

Cited by 26 publications

References 9 publications

In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

Targeting melanoma with immunoliposomes coupled to anti-MAGE A1 TCR-like single-chain antibody

Immunoliposomes for Specific Drug Delivery

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