A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

Wang, Shanmei; He, Xian; Li, Nan; Yu, Feng; Hu, Yang; Wang, Liu-Sheng; Zhang, Peng; Du, Yuxuan; Du, Shan-Shan; Yin, Zhimin; Wei, Yaru; Mulet, Xavier; Coia, Gregory; Wu, Dong; He, Jia; Wu, Min; Li, Huiping

doi:10.2147/ijn.s77268

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…Another example for the use of nanobodies in the development of lung-targeting drugs is the targeting of pulmonary surfactant protein A (SPA) [115]. Due to the exclusive expression of SPA on alveolar epithelial type II cells, it can serve as a molecule for specific targeting of lung diseases.…”

Section: Nanobodies Against Lung Diseasesmentioning

confidence: 99%

“…Due to the exclusive expression of SPA on alveolar epithelial type II cells, it can serve as a molecule for specific targeting of lung diseases. In one study, the authors selected two nanobodies, Nb6 and Nb17, that showed high specificity for SPA [115]. To evaluate the lung-targeting ability of Nb17, the authors performed in vivo imaging using murine models and showed fast accumulation of Nb17 in the lungs, and complete clearance from the blood circulation within 6 h after injection.…”

Section: Nanobodies Against Lung Diseasesmentioning

confidence: 99%

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The Therapeutic Potential of Nanobodies

2019

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Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety-characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

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Section: Nanobodies Against Lung Diseasesmentioning

confidence: 99%

Section: Nanobodies Against Lung Diseasesmentioning

confidence: 99%

The Therapeutic Potential of Nanobodies

2019

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“…In our previous study, we successfully constructed an Nb library for rat pulmonary surfactant protein A and identified Nb17 as a specific Nb for rat pulmonary SP-A. Nb17 is very specific, shows high affinity to the target protein, and has a satisfactory safety profile 22 . The current study was based on our previous experience on Nb17 and took the advantages of the very high homology (98%) of rat and human pulmonary SP-A protein to identify Nb4, which specifically binds human pulmonary SP-A.…”

Section: Discussionmentioning

confidence: 99%

“…Human pulmonary tissue frozen sections were used for biopanning of our previously constructed phage-display Nb library 22 . The frozen tissue sections were washed 10 times with sterile PBS and then incubated with 2 mL solution containing the Nb library at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

Identification of a nanobody specific to human pulmonary surfactant protein A

He¹,

Wang

Yin³

et al. 2017

Sci Rep

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Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10−7 M. Nb4 (19 kDa) was stable at 30 °C–37 °C and pH 7.0–7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn’t react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn’t cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung.

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“…In addition, to develop lung-targeting drugs, Nbs targeting pulmonary surfactant protein A (SPA) have been isolated. The authors showed fast accumulation of selected Nbs in the lungs (Wang et al 2015). Nbs against different coronavirus species have been isolated and characterized to block interaction between virus and host cell.…”

Section: Neutralizing Vhh Against Viral Zoonosismentioning

confidence: 99%

Perspective on therapeutic and diagnostic potential of camel nanobodies for coronavirus disease-19 (COVID-19)

et al. 2021

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In this paper, we focus on the camelid nanobodies as a revolutionary therapy that can guide efforts to discover new drugs for Coronavirus disease . The small size property makes nanobodies capable of penetrating efficiently into tissues and recognizing cryptic antigens. Strong antigen affinity and stability in the gastrointestinal tract allow them to be used via oral administration. In fact, the use of nanobodies as inhalant can be directly delivered to the target organ, conferring high pulmonary drug concentrations and low systemic drug concentrations and minimal systemic side effects. For that, nanobodies are referred as a class of next-generation antibodies. Nanobodies permit the construction of multivalent formats that may achieve ultra-high neutralization potency and then may prevent mutational escape and can neutralize a wide range of SARS-CoV-2 variants. Due to their distinctive characteristics, nanobodies can be of great use in the development of promising treatment or preventive strategies against SARS-CoV-2 infection. In this review, the state-of-the-art of camel nanobodies design strategies against the virus including SARS-CoV-2 are critically summarized. The application of general nanotechnology was also discussed to mitigate and control emerging SARS-CoV-2 infection.

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A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

Cited by 6 publications

References 43 publications

The Therapeutic Potential of Nanobodies

The Therapeutic Potential of Nanobodies

Identification of a nanobody specific to human pulmonary surfactant protein A

Perspective on therapeutic and diagnostic potential of camel nanobodies for coronavirus disease-19 (COVID-19)

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