Site-Directed Conjugation of Antibodies to Apoferritin Nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells

Dostálová, Simona; Černá, Tereza; Hynek, David; Koudelková, Zuzana; Vaculovič, Tomáš; Kopel, Pavel; Hraběta, Jan; Heger, Zbyněk; Vaculovičová, Markéta; Eckschlager, Tomáš; Stiborová, Marie; Adam, Vojtěch

doi:10.1021/acsami.6b04286

Cited by 63 publications

(69 citation statements)

References 59 publications

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“…The peptide (KHRFNKD) immobilized with biotin to an avidin-QCM surface showed improved IgG binding relative to physical adsorption. Dostalova et al 112 used the Fc binding peptide HWRGWVC to immobilize antiprostate specific membrane antigen antibodies to gold coated doxorubicin nanocarriers with solution-phase orientation. The inclusion of the peptide gave a 1.4-fold improvement in signal during the immunoassay.…”

Section: Fc-binding Peptides and Aptamersmentioning

confidence: 99%

Orientation and characterization of immobilized antibodies for improved immunoassays (Review)

et al. 2017

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Orientation of surface immobilized capture proteins, such as antibodies, plays a critical role in the performance of immunoassays. The sensitivity of immunodiagnostic procedures is dependent on presentation of the antibody, with optimum performance requiring the antigen binding sites be directed toward the solution phase. This review describes the most recent methods for oriented antibody immobilization and the characterization techniques employed for investigation of the antibody state. The introduction describes the importance of oriented antibodies for maximizing biosensor capabilities. Methods for improving antibody binding are discussed, including surface modification and design (with sections on surface treatments, three-dimensional substrates, self-assembled monolayers, and molecular imprinting), covalent attachment (including targeting amine, carboxyl, thiol and carbohydrates, as well as “click” chemistries), and (bio)affinity techniques (with sections on material binding peptides, biotin-streptavidin interaction, DNA directed immobilization, Protein A and G, Fc binding peptides, aptamers, and metal affinity). Characterization techniques for investigating antibody orientation are discussed, including x-ray photoelectron spectroscopy, spectroscopic ellipsometry, dual polarization interferometry, neutron reflectometry, atomic force microscopy, and time-of-flight secondary-ion mass spectrometry. Future perspectives and recommendations are offered in conclusion.

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Section: Fc-binding Peptides and Aptamersmentioning

confidence: 99%

Orientation and characterization of immobilized antibodies for improved immunoassays (Review)

et al. 2017

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“…53 In our previous work, we proved that the encapsulation of Dox inside Apo has similar influence on cancer cells as free Dox, whereas normal, noncancer cells are significantly protected from Dox influence. 21 Therefore, in the present experiment we tested the internalization of ApoDox stored at various conditions using only the androgen-dependent metastatic prostate cancer cell line LNCaP.…”

Section: Apodox Stored In Pbs (mentioning

confidence: 99%

“…These nanosized carriers can target diseased tissue and cells via passive targeting (due to their size) 20 or active targeting (due to specific moieties on their surface). 21 Various materials have been tested for targeted Dox delivery, including inorganic, 22 polymeric, 23 lipid-based, 24 or proteins. 25 The first US Food and Drug Administration-approved nanoformulation was liposome-encapsulated Dox (Doxil ® / Caelyx ® or Myocet ® ).…”

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confidence: 99%

“…We proved that surface-modified ApoDox retained the high toxicity of Dox for targeted cancer cells while sparing 50% of nonmalignant cells. 21 In this work, we evaluated the long-term stability of ApoDox. For 12 weeks, we continuously monitored changes in undesirable premature Dox release during storage, its optical properties, and the size and ζ-potential of the Apo nanocarrier, as well as its toxicity for prostate cell lines.…”

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confidence: 99%

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Apoferritin as an ubiquitous nanocarrier with excellent shelf life

Dostálová¹,

Vašíčková²,

Hynek³

et al. 2017

IJN

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Due to many adverse effects of conventional chemotherapy, novel methods of targeting drugs to cancer cells are being investigated. Nanosize carriers are a suitable platform for this specific delivery. Herein, we evaluated the long-term stability of the naturally found protein nanocarrier apoferritin (Apo) with encapsulated doxorubicin (Dox). The encapsulation was performed using Apo’s ability to disassemble reversibly into its subunits at low pH (2.7) and reassemble in neutral pH (7.2), physically entrapping drug molecules in its cavity (creating ApoDox). In this study, ApoDox was prepared in water and phosphate-buffered saline and stored for 12 weeks in various conditions (−20°C, 4°C, 20°C, and 37°C in dark, and 4°C and 20°C under ambient light). During storage, a very low amount of prematurely released drug molecules were detected (maximum of 7.5% for ApoDox prepared in PBS and 4.4% for ApoDox prepared in water). Fourier-transform infrared spectra revealed no significant differences in any of the samples after storage. Most of the ApoDox prepared in phosphate-buffered saline and ApoDox prepared in water and stored at −20°C formed very large aggregates (up to 487% of original size). Only ApoDox prepared in water and stored at 4°C showed no significant increase in size or shape. Although this storage caused slower internalization to LNCaP prostate cancer cells, ApoDox (2.5 μM of Dox) still retained its ability to inhibit completely the growth of 1.5×10 4 LNCaP cells after 72 hours. ApoDox stored at 20°C and 37°C in water was not able to deliver Dox inside the nucleus, and thus did not inhibit the growth of the LNCaP cells. Overall, our study demonstrates that ApoDox has very good stability over the course of 12 weeks when stored properly (at 4°C), and is thus suitable for use as a nanocarrier in the specific delivery of anticancer drugs to patients.

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“…Hybrid lipid-polymer nanoformulations combine the advantages of both models, allowing controlled drug release and enhanced bio-functionality 15 . Recent evidence shows that nanoformulations provide significant advantage to prostate cancer molecular therapies and chemotherapies allowing improvement in drug delivery and imaging 16–18 . This is particularly true for docetaxel where nanoformulations outperform systemic therapy 19, 20 .…”

Section: Introductionmentioning

confidence: 99%

Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

Wang

Alshaker

Böhler

et al. 2017

Sci Rep

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Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose. Our CSLPHNPs showed high serum stability and a long shelf life. CSLPHNPs demonstrated a steady uptake by tumor cells, sustained intracellular drug release and in vitro efficacy superior to free therapies. In a mouse model of human prostate cancer, CSLPHNPs showed excellent tumor targeting and significantly lower side effects compared to free drugs, importantly, reversing lymphopenia induced by FTY720. Overall, we demonstrate that nanoparticle encapsulation can improve targeting, provide low off-target toxicity and most importantly reduce FTY720-induced lymphopenia, suggesting its potential use in clinical cancer treatment.

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Site-Directed Conjugation of Antibodies to Apoferritin Nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells

Cited by 63 publications

References 59 publications

Orientation and characterization of immobilized antibodies for improved immunoassays (Review)

Orientation and characterization of immobilized antibodies for improved immunoassays (Review)

Apoferritin as an ubiquitous nanocarrier with excellent shelf life

Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

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