AUTONOMOUS DRUG-ENCAPSULATED NANOPARTICLES: TOWARDS A NOVEL NON-INVASIVE APPROACH TO PREVENT ATHEROSCLEROSIS

Introduction This paper proposes the concept of autonomous drug-encapsulated nanoparticle (ADENP) as a novel non-invasive approach to prevent atherosclerosis. ADENP consists of three simple units of sensor, controller (computing), and actuator. The hardware complexity of ADENP is much lower than most of the nanorobots, while the performance is maintained by the synergism in the swarm architecture. Materials and Methods Since high accumulation of low density lipoprotein (LDL) macromolecules within the arterial wall plays a critical role in the initiation and development of atherosclerotic plaques, the task of the swarm of ADENPs is autonomous feedback control of LDL level in the interior of the arterial wall. In this study, we consider two specific types of ADENPs with distinguishing capabilities. The performance of each type is evaluated and compared on a well-known mathematical model of the arterial wall through computer simulation. Results Simulation results demonstrate that the proposed approach can successfully reduce the LDL level to a desired value in the arterial wall of a patient with very high LDL level that is corresponding to the highest rates of cardiovascular disease events. Moreover, it is shown that ADENP is capable of distinguishing between healthy and unhealthy arterial walls to reduce the drug side effects. Conclusion The proposed approach is a promising autonomous non-invasive method to prevent and treat complex diseases such as atherosclerosis.

[1]  Y. Yamauchi,et al.  Preparation of aqueous colloidal mesostructured and mesoporous silica nanoparticles with controlled particle size in a very wide range from 20 nm to 700 nm. , 2013, Nanoscale.

[2]  Lulu Qian,et al.  A Simple DNA Gate Motif for Synthesizing Large-Scale Circuits , 2008, DNA.

[3]  Formulation of nanoparticle-eluting stents by a cationic electrodeposition coating technology: efficient nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries. , 2009, JACC. Cardiovascular interventions.

[4]  Kambiz Vafai,et al.  Modeling of low-density lipoprotein (LDL) transport in the artery—effects of hypertension , 2006 .

[5]  M. Nakano,et al.  Drug Delivery System Using Nano-Magnetic Fluid , 2008, 2008 3rd International Conference on Innovative Computing Information and Control.

[6]  Luis M Liz-Marzán,et al.  Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth. , 2018, Nature materials.

[7]  Victor M. Calo,et al.  Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls , 2012 .

[8]  Vladimir A Basiuk,et al.  Self-assemblies of meso-tetraphenylporphine ligand on surfaces of highly oriented pyrolytic graphite and single-walled carbon nanotubes: insights from scanning tunneling microscopy and molecular modeling. , 2011, Journal of nanoscience and nanotechnology.

[9]  Kevin M. Passino,et al.  Swarm Stability and Optimization , 2011 .

[10]  Sun Yu Supramolecular Nanovalve Systems Based on Macrocyclic Synthetic Receptors , 2012 .

[11]  S. Liao,et al.  A biocompatible drug delivery nanovalve system on the surface of mesoporous nanoparticles , 2012 .

[12]  Yan Liu,et al.  Three-input majority logic gate and multiple input logic circuit based on DNA strand displacement. , 2013, Nano letters.

[13]  A. Sen,et al.  Alternative for by-pass surgery using iron-oxide nano-particles , 2006, 2006 Bio Micro and Nanosystems Conference.

[15]  A. Cavalcanti,et al.  Nanorobotics control design: a collective behavior approach for medicine , 2005, IEEE Transactions on NanoBioscience.

[16]  Nataša Jonoska,et al.  Computing by molecular self-assembly , 2012, Interface Focus.

[17]  Kambiz Vafai,et al.  A coupling model for macromolecule transport in a stenosed arterial wall , 2006 .

[18]  Lulu Qian,et al.  Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades , 2022 .

[19]  R. Freitas Pharmacytes: an ideal vehicle for targeted drug delivery. , 2006, Journal of nanoscience and nanotechnology.

[20]  Bijan Shirinzadeh,et al.  Nanorobot Hardware Architecture for Medical Defense , 2008, Sensors.

[21]  R. Sinden DNA Structure and Function , 1994 .

[22]  B. Shirinzadeh,et al.  Hardware architecture for nanorobot application in cerebral aneurysm , 2007, 2007 7th IEEE Conference on Nanotechnology (IEEE NANO).

[23]  Luca Cardelli,et al.  Abstractions for DNA circuit design , 2011, Journal of The Royal Society Interface.

[24]  Christopher A. Voigt,et al.  Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ , 2011, Nature.

[25]  A living biological nano robot as self-navigator sensor for diseases , 2011, 2011 1st Middle East Conference on Biomedical Engineering.

[26]  G. Findenegg,et al.  Lysozyme as a pH-responsive valve for the controlled release of guest molecules from mesoporous silica. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[27]  Veysel Gazi,et al.  Swarm aggregations using artificial potentials and sliding mode control , 2003, 42nd IEEE International Conference on Decision and Control (IEEE Cat. No.03CH37475).

[28]  Kevin M. Passino,et al.  Stability analysis of swarms , 2002, Proceedings of the 2002 American Control Conference (IEEE Cat. No.CH37301).

[29]  Bijan Shirinzadeh,et al.  Nanorobot for treatment of patients with artery occlusion , 2006 .

[30]  H Suraj.,et al.  QCA based navigation for nano robot for the treatment of coronary artery disease , 2011, 2011 IEEE International Symposium on Medical Measurements and Applications.

[31]  D. Endy,et al.  Rewritable digital data storage in live cells via engineered control of recombination directionality , 2012, Proceedings of the National Academy of Sciences.

[32]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[33]  N. Stanietsky,et al.  The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity , 2009, Proceedings of the National Academy of Sciences.

[34]  Baris Fidan,et al.  Aggregation, Foraging, and Formation Control of Swarms with Non-Holonomic Agents Using Potential Functions and Sliding Mode Techniques ∗† , 2007 .

[35]  E. Ruoslahti,et al.  Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice , 2011, Proceedings of the National Academy of Sciences.

[36]  Z. Kovács,et al.  Improving the Design of a MscL-Based Triggered Nanovalve , 2013, Biosensors.

[37]  E. Garfunkel,et al.  Versatile fluorescence resonance energy transfer-based mesoporous silica nanoparticles for real-time monitoring of drug release. , 2013, ACS nano.

[38]  P. Blount,et al.  Manipulating the permeation of charged compounds through the MscL nanovalve , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  Robert DeRose,et al.  Rapid and orthogonal logic gating with a gibberellin-induced dimerization system. , 2012, Nature chemical biology.

[40]  Zongxi Li,et al.  Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. , 2010, Small.

[41]  Kambiz Vafai,et al.  Low-density lipoprotein (LDL) transport in an artery – A simplified analytical solution , 2008 .

[42]  Sylvain Martel Aggregates of Synthetic Microscale Nanorobots versus Swarms of Computer-Controlled Flagellated Bacterial Robots for Target Therapies through the Human Vascular Network , 2010, 2010 Fourth International Conference on Quantum, Nano and Micro Technologies.

[43]  Mohammad-R Akbarzadeh-T,et al.  Control of Low-Density Lipoprotein Concentration in the Arterial Wall by Proportional Drug-Encapsulated Nanoparticles , 2012, IEEE Transactions on NanoBioscience.

[44]  D. Arifin,et al.  MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted cell viability , 2012, Nature materials.

[45]  Teruo Fujii,et al.  Bottom-up construction of in vitro switchable memories , 2012, Proceedings of the National Academy of Sciences.

[46]  Freitas Robert A.Jr CURRENT STATUS OF NANOMEDICINE AND MEDICAL NANOROBOTICS , 2005 .

[47]  S. Agrawal,et al.  Nanosensors and their Pharmaceutical Applications: A Review , 2012 .