Nanorobots for Biomedical Applications

M.P. Nikitin1,2,3
1

Nanobiotechnology Laboratory, Moscow Institute of Physics and Technology (State University), MIPT, Dolgoprudny, Russia
2
Biophotonics Laboratory, Prokhorov General Physics Institute RAS, GPI RAS, Moscow, Russia
3
Molecular Immunology Lab., Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, IBCH RAS, Moscow, Russia
e-mail: max.nikitin@phystech.edu

Abstract Conceptually novel approach has been

demonstrated to create nanobiorobotic structures for targeted
drug delivery and biosensing. The proposed nanostructures are
capable of performing multi-parametric molecular analysis of
the micro-environment of a therapeutic target (e.g., a cancer cell)
and react to it in a pre-programmed way.
Keywords targeted drug delivery, theranostics, nanoparticles,
biocomputing nanostructures, boolean logic functions, biorobots

I.

INTRODUCTION

Nowadays, targeted drug delivery to different sites of the

organism is among the topical problems of biomedical
research. Along with reliable diagnostics, drug delivery
directly to the site of the required therapeutic intervention is a
crucial factor for prognosis of illness, including oncological
and cardiovascular diseases. One of the promising solutions is
theranostics, which combines diagnostics with therapeutic
effect on the determined physiological targets. In this work, the
biocomputing micro- and nanostructure approach for
diagnostics and targeted drug delivery originally proposed in
[1] has been optimized and tested.
II.

RESULTS AND DISCUSSION

We have developed a variety of novel biocomputing

structures that can implement a functionally complete set of
Boolean logic gates (YES, NOT, AND and OR) and bind to a
target as a result of the computation. The logic gating
functionality
is
incorporated
into
self-assembled
particle/biomolecule interfaces and is realized through an
input-induced disassembly of the structures. Different types of
ligand-receptor interfaces were tested, which showed
acceptable binding specificity comparable with [2]. The
biocomputing structures employed various carriers and
shielding agents, including fluorescent (FNP), gold (GNP),
magnetic (MNP) nanoparticles as well as nanoparticles
conjugated with color-generating enzymes. The stimuli
responsive reversible processes of self-assembly and
disintegration of the Biocomputing structures have been
investigated. To verify interaction of various functionalized
particles and to study of kinetics and affinity constants of the
involved biomolecules we have used the spectral correlation
interferometric method, which provides information on the
average thickness of surface biolayers [3]. The biocomputation
results implemented with MNP were monitored by their nonlinear magnetization by magnetic particle quantification
(MPQ) readers [1, 4]. The preference to MNP was given as
some of them were already approved in many countries for

intravenous injections in humans and because of their attractive

biodegradation profile in vivo [5].
In the experiments, the MNP-based structures were
monitored deep in the body and bloodstream of experimental
animals (rats and mice) with the MPQ, while the structures
based on FNP and GNP were investigated in vitro by
spectroscopic setups. The biocomputing structures based on the
stimuli responsive composite nanoparticle/biomolecule
interfaces offer remarkably complex information processing.
The signal transduction between several orthogonal receptors
that do not share any specific biochemistry has been achieved,
among other means, by spatial entanglement of the receptors.
Based on the biocomputing structures, new biosensors for
detection of small molecules were developed. The optimized
structures were tested for design of autonomous nanodevices as
nanorobotic agents with built-in biochemical data analysis for
stimuli-controlled targeted drug delivery.
III.

CONCLUSIONS

We have shown that the biocomputingcapable

nanoparticles are promising for creation of sophisticated
nanorobotic devices ranging from intelligent nanobiosensors to
smart programmable theranostic agents. The approach was
experimentally illustrated for advanced immunoassays and
logic-gated cell targeting. Such smart nanostructures may offer
new opportunities for a new-generation theranostic systems
that feature targeted and controllable delivery of nanobioagents
in the organism depending on the result of autonomous
analysis of the physiological factors according to the preprogrammed Boolean logic functions.
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[1]
[2]

[3]

[4]

[5]

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The work was supported by the Russian Science Foundation grant No:
16-19-00131
S2-27