In vivo nano-biosensing element of red blood cell-mediated delivery
Introduction
A nanobiosensor is an analytical device in nanometer scales used to probe or measure biochemical substances, usually comprises a sensing element “bio-receptor” to interact with the targeted analyte and produce a detectable physical signal to be transformed by a transducer component, making it possible to convert and quantify the biological and biochemical signals through optical, electronic, thermal, or magnetic methods (Prasad, 2014). In recent years, together with the progress in the nano-technology, nanobiosensors that can be used in vivo are vigorously developing as they can provide real-time, rapid, and accurate analysis of physiological and pathological processes in living organisms, which has been a hot research topic in medical and ecological diagnostics (Sadovoy and Teh, 2015; Gurkov et al., 2016, 2017; Volkova et al., 2017).
In the emerging field of nanomedicine, novel nano-agents are intensively developed and manufactured for potential biomedical applications including nano-biosensing, nano-diagnostics, and personalized therapy while lacking comprehensive assessment of their potential health risks. In recent years, the application of smart drug delivery systems (DDSs) in the field of in vivo biosensing has attracted extensive attention and been widely studied to promote the clinical early diagnosis and therapy, especially early cancer screening and treatment (Argyo et al., 2014; Wang et al., 2019). Controllable, precise, and safe delivery of diagnostic nano devices and therapeutic agents to the target tissues, organs, or cells is an important determinant in every clinical approach. In recent years, inspired by the red blood cell (RBC)-mediated delivery methods, nanomaterial-based theragnostic platforms for bio-sensing applications including bio-imaging at the single-cell level, advanced medical diagnostics, and analytical detection of biomolecules and cellular activities are facing new development opportunities.
At present, there are many reviews on the medical applications based on the development of new sensing techniques capable of performing very sensitive detection and quantifying certain parameters, especially based on smart nanobiosensors (Ahmed et al., 2014; Attaallah et al., 2020; Chamorro-Garcia and Merkoçi, 2016; Ghorbani et al., 2019; Maxwell et al., 2002; Prasad, 2014). Numbers of reviews have summarized the cell-based DDSs in general (Glassman et al., 2020; Jahangirian et al., 2019; Kurapati et al., 2019; Sun et al., 2017). However, currently, there are only a few of reviews place emphasis on the RBC-mediated delivery for specific application areas and the adverse effects on human health induced by the interaction of delivered sensing devices and theranostic agents with blood components.
In this review, the emphasis is placed on the nanomaterial-based in vivo biosensing elements for applications of bio-imaging at the single-cell level, advanced medical diagnostics, and analytical detection of biomolecules and cellular activities that benefited from the RBC-mediated DDSs. Specifically, the technical framework of the state-of-the-art developments of RBC-mediated delivery of theragnostic nano devices/agents is presented. Finally, the advantages, challenges, and the development trends of nanobiosensors based on the RBC-mediated delivery are indicated to inspire the design and implementation of advanced nano-biosensing platforms taking advantage of RBC-delivery modalities.
Section snippets
The application of nanomaterials in biosensing
The revolutionary development of nanotechnology has encouraged tremendous progress in the design of in vivo/vitro diagnostic/therapeutic tools utilizing nanostructures with various types and materials (Anselmo and Mitragotri, 2016; Lucky et al., 2015; Wolfbeis, 2015; Zhou et al., 2015). To date, distinguished by different dimensions and geometry, diverse types of nanomaterials including nanoparticles (NPs), nanofiber, nanotubes, nanorods, and nanoribbon have been studied (Wolfbeis, 2015). Among
RBC-mediated delivery of nanobiosensors and nanoprobes for bio-imaging at the single-cell level
Biosensor systems are widely used in multi-modal bio-imaging at the single-cell level including imaging and tracking of single molecules and molecular interactions, visualizing and monitoring specific enzyme activities, and dynamic imaging of bio-fluids for clinical applications (Stawarski et al., 2014; Tran et al., 2018). With the support of nanomaterials, the design of this kind of biosensor imaging system is more diversified and the performance is further promoted. For example, organic
Principles of cargo loading onto RBCs
Various procedures have been proposed to deliver and transport therapeutic and diagnostic nano-agents through human RBCs so that they can circulate with natural RBCs in the bloodstream for a long time, reach the target position, and be released and accumulated in certain tissues or organs to achieve excellent therapeutic or diagnostic performances (Hu et al., 2012). Numerous therapeutic agents including proteins, nucleic acid, viral agents, and novel nano-drugs have been explored to be carried
Advantages of RBC-mediated delivery of biosensing nano-agents
Circulation prolongation is one of the main advantages of RBC-delivered biosensing nano-agents. For intravenous injection of free NPs, the particle uptake in liver and spleen is the most significant and shows particle size-dependent organ distribution. Among different sized (10–250 nm) spherical-shaped gold NPs (Au-NPs), large NPs mainly distributed in blood, liver, and spleen, whereas smaller (10 nm) Au-NPs were found in various organs including blood, liver, spleen, kidney, testis, heart,
Conclusions and perspectives
In conclusion, with the rapid development in the emerging field of nanomedicine, novel NPs have been investigated in preclinical studies and are being transformed to a great variety of clinical applications including cancer imaging (e.g., with silica NPs) and thermal ablation of tumors (e.g., with gold and iron-oxide NPs). Currently, transport and delivery of NP-based theranostic agents via their covalent or physical interactions with RBCs have been developed rapidly and are currently in
Funding
This work was partially funded by the China Scholarship Council (CSC No. 201706410089, R.Z.), STSM Grant from COST Action CA 17,140 ″Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology) (grant No. ECOST-STSM-CA17140-230,919-113049, R.Z.). EDUFI Fellowship (TM-17-10,370, TM-18-10,820, T.A.) and Suomen Kulttuurirahasto (grant No. 00190188, T.A.). The authors also acknowledge the contribution of Russian Science Foundation (Projects:
Author contributions
R.Z; Writing – original draft preparation, Writing – review & editing, T.A; Writing – review & editing, A.P; Supervision, A.B; Supervision, I.M; Writing – review & editing, Supervision, Funding acquisition, All authors have read and agreed to the published version of the manuscript.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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