Nanobodies; new molecular instruments with special specifications for targeting, diagnosis and treatment of triple-negative breast cancer

Abstract

Breast cancer is the most common type of cancer in women and the second leading cause of cancer death in female. Triple-negative breast cancer has a more aggressive proliferation and a poorer clinical diagnosis than other breast cancers. The most common treatments for TNBC are chemotherapy, surgical removal, and radiation therapy, which impose many side effects and costs on patients. Nanobodies have superior advantages, which makes them attractive for use in therapeutic agents and diagnostic kits. There are numerous techniques suggested by investigators for early detection of breast cancer. Nevertheless, there are fewer molecular diagnostic methods in the case of TNBC due to the lack of expression of famous breast cancer antigens in TNBC. Although conventional antibodies have a high ability to detect tumor cell markers, their large size, instability, and costly production cause a lot of problems. Since the HER-2 do not express in TNBC diagnosis, the production of nanobodies for the diagnosis and treatment of cancer cells should be performed against other antigens expressed in TNBC. In this review, nanobodies which developed against triple negative breast cancer, were classified based on type of antigen.

Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging

“…The major milestones towards the clinical translation of nanobody-based PET probes are currently the phase II study of a 68 Ga-NOTA-labeled anti-HER2 nanobody in HER2-positive breast cancer patients ( 40 ) and the phase I/II study of a [ 68 Ga]Ga-NOTA-anti-MMR (Macrophage Mannose Receptor) for the detection of tumor-associated macrophages (TAM) ( 41 ). In the case of TNBC, nanobodies against tumor-specific antigens such as TNF-α, EGFR, CD3, CTLA-4, STAT-3, AKT2 among others, have been generated and tested for targeting cancer cells ( 22 ). Herein, we propose the development of MT1-MMP-specific nanobodies as candidates for TNBC diagnosis by non-invasive diagnostic imaging.…”

“…Owing to their unique and well-characterized properties, nanobodies have become extremely useful tools in diagnostics, therapeutics and research; especially in TNBC (see ( 22 ) for review). Here, we report the generation and characterization of MT1-MMP-targeting nanobodies from a llama immunized with the catalytic domain of MT1-MMP at the VIB Nanobody Core (Vrije Universiteit Brussel), and the development of 68 Ga-labeled nanobody tracers to specifically detect MT1-MMP expression in a TNBC xenograft model for imaging diagnostic purposes by ImmunoPET.…”

A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era

“…In 1907, Paul Ehrlich, whose work was related to the development of chemotherapy and specific targeted treatment concepts [54], introduced the term "magic bullet" as a drug specifically targeting a particular pathogen, without affecting the normal cells of the host, anticipating the era of the development of site-specific therapies for cancer treatment [55,56]. Today, the use of nanomedicine and nano(bio)technology in the BC field involves handling modern and challenging variants of Ehrlich s "magic bullet", which can be considered as nano-"magic bullets" that are able to perform multiple and targeted functions and tasks, such as different types of nanorobots/nanobots/nanovehicles/nanomachines/nanomotors/nanodevices or nanosubmarines/nanosubs [21,57], nanotrains [58], nanostars [59], enzymatic, magnetic or DNAzyme based nanoflowers/nanoclusters [60][61][62], urchin-head/hollow tail nanorobots with sharp nanospikes [12], nanospheres [63], nanocubes [64], nanorods [65], nanoneedles [66], nanotubes [67], worm-like nanocrystal micelles [68], nanoshells [43], nanosponges and nanokillers [47], nanoknives [69], nanoballons [70], nanozymes [71], nano-snowflakes [25], nanobubbles [72,73], nanoemulsions [74], nanobodies [75], nanobiosensors [76], nanopores [77], nanocages [33], nanotraps [34],or nanogenerators [78] (Figure 1). Undoubtedly, the use of nanoparticulate-based platforms has provide more and more advantages to the BC field including great biocompatibility and biodistibution, multifunctionality, the ability to overcome biological barriers and bioaccumulate in multiple tumor sites, even in the nucleus and specific organel...…”

“…Bioorthogonal nanozymes, obtained from the encapsulation of transition metal catalysts into nanomaterials, act as "drug factories" that remain present at the tumor site at least one week after a direct injection, continuously converting the non-toxic molecules in the prodrug into active drugs at the injection site [71]. Nanobodies, a novel class of antibodies used for immunohistochemical detection that were discovered in camelids, are able to detect haptens and cryptic epitopes, which are not detectable by classical antibodies [75]. Under a microscope, nanoflowers (NFs), a distinctive subtype of nanomaterials, resemble flowers with a branched aspect and tailored petal structure that have a high surface-to-volume ratio [60].…”

Nanobody Engineering: Computational Modelling and Design for Biomedical and Therapeutic Applications

“…Apart from their clear usefulness in basic biochemical research, nanobodies are increasingly employed as diagnostic tools [45,46], molecular imaging probes [46], and therapeutic agents [45][46][47][48]. They are currently under clinical investigation for a diverse range of human diseases [3], including conditions such as breast cancer [49], brain tumours [24], lung diseases [50], and infectious diseases [51]. Nanobodies can also target various tumours [9,52] and are used in the diagnosis and treatment of prostate cancer [7].…”