Study On Key Technology Of Local Targeted Drug Delivery Based On Molecular Communication And Multi-nanorobot

Traditional drug delivery systems like injecting drugs into blood vessels are often inefficient as they mainly rely on molecular diffusion processes to deliver drugs.Targeted drug delivery can reduce side effects on healthy tissues by PEGylation(i.e.,modifying the surface of drug carriers).Current targeted drug delivery like passive targeting and active targeting are still low efficient because only a small fraction(10%)of the administered drugs actually reach tumor target site.It is significant that drug delivery carriers are capable of swimming towards target site(e.g.,diseased cells or tumors).New-generation targeted drug delivery systems will be capable of autonomously swimming towards the target site and penetrating tissue,independent of blood and lymphatic flow.This has been shown to some extent with modified bacteria and nanorobots with the development of nanotechnology.Multi-nanorobot's aggregation and drug release at targeted site are key issues in local targeted drug delivery by nanorobots.Molecular communication is an emerging communication paradigm and is considered as a promising approach in nanorobot-based targeted drug delivery for both aggregation and drug release at targeted site.This thesis investigates the key technology of local targeted drug delivery based on molecular communication and multi-nanorobot.The strategy of multi-nanorobot aggregation at target site is one of key technologies in local targeted drug delivery based on multi-nanorobot.This thesis proposes a nanorobot control strategy designed for aggregating at tumor target site in local blood vessel for targeted drug delivery.The strategy coordinates nanorobots' movements through use of two types of chemical molecules,an acoustic signal and velocity characteristic of blood fluid.After detecting the chemical molecules called tumor biomarker released by tumor cells,a nanorobot moves towards the area of higher concentration of the molecule and releases another chemincal molecule which alerts others to aggregate to tumor target site.When nanorobots which do not detect chemical molecules detect acoustic signals emitted by nanorobots reaching target site,their paths will be planned to aggregate to target site according to intensity of accoustic signals and velocity characteristic of blood fluid.When aggregating at target site,nanorobots would release drug molecules which chemically react to tumor cells.If the nanorobots release drug molecules faster than the tumor cells react,the excess drug molecules remain in the environment and eventually degradation or diffuse away,which results in loss of drug molecules or degradation in efficiency.Otherwise,it results in a lower reaction rate.It is a potential issue associated with the relationship among release rate,reaction rate and efficiency.To this end,this thesis aims to investigate the relationship through two drug reception models whereby the first one is based with respect to collision with tumors while the second is based on Michaelis Menten enzymatic kinetics.It is expected to pave a way for designing a control method of drug release.If nanorobots release drugs as soon as they arrive at target site,the proper drug dosage may actually not be delivered to the target since not all nanorobots can reach the target at the same time.To this end,this thesis proposes a nanorobot-based system comprising of nanorobot behavior selection strategy,drug reception model and adjusting method of drug release rate for a simulation of local targeted drug delivery.In the system,nanorobots can move and accumulate at target site by simulating bacterial chemotaxis,and determine the timing of drug release relying on quorum sensing.In addition,nanorobots can dynamically adjust the rate of drug release depending on the concentration of tumor biomarker.The drug effects are closely related to the interactions of drug molecules with receptors at target cells in the process of drug release.According to the occupancy theory,the drug effects is proportional to the rate of receptors occupied by drug molecules and not necessary to reach an occupancy of 100% of receptors to produce a full reponse on the target cell for some types of drugs.This thesis proposes a method to calculate the optimal initial release rate of drug molecules to produce a full drug response.In the method,first,a drug reception model based on M/M/r/r queue to simulate the interactions between ligands and receptors is established;second,the least effective concentration(LEC)of drug molecules is derived from the least ratio of receptors occupied by drug molecules to produce full drug response according to the occupancy theory;finally,the optimal initial release rate of drug molecules is derived from the least concentration of drug molecules according to molecular diffusion law.