Application of nanotechnology in drug delivery

: nanoneedles and nano-medicine

Abstract

Cancer, one of the highest death rates, common diseases in the world, is known to be difficult to cure. Chemotherapy is the major solution for cancer treatment. Nevertheless, substantial obstacles such as the low antitumor efficacy and related systemic toxicities of the free drug, are still imperative problems that still remain unsolved. Enormous efforts have been made to increase the successful delivery efficiency of drugs across the cell membrane into cancer cells. However, anti-cancer drugs are often hydrophobic, which are poorly delivered into the cells due to inherent issues such as low water solubility and/or unwanted toxicity. Nowadays, scientists try to develop various methods and approaches to boost the cellular uptake of the drug molecules by applying the concept of nano-drug system. Here, we demonstrate the application of nanoneedles and nano-medicine in the field of drug delivery in cancer treatment and how they enhance the drug delivery efficacy. Firstly, we studied the physical approaches to successful deliver various drug molecules into cells via sharp diamond nanoneedles treatment. In this treatment, cell membrane of cells is disrupted for a short period of time, allowing drug molecules to directly pass through the cell membrane thus drug molecules successful entered into the cells. This is a direct and effective way to enhance the efficacy of drug delivery. In our experiment, diamond nanoneedles are chosen as their excellent physical properties with no harm to the cells. After the cells undergo nanoneedles treatment, they remain alive in cell viability measurement (MTT assay) proving that the nanoneedles only cause repairable disrupt to the cells. With the cells incubated with anticancer drug with sharp nanoneedles treatment, higher death rate was observed than the cells without nanoneedles treatment. We concluded that the promising improvement of cytotoxicity is due to the diamond nanoneedles successfully disrupt the cell membrane temporarily and allow more drug molecules to direct enter the cancer cell. Secondly, we synthesized carrier-free, pure drug nanoparticles for enhancing drug delivery efficacy. Nano-sized drug delivery system has received extensive attentions recently due to their unique accumulation behavior at tumor site. Enhance permeation and retention (EPR) effect is considered as a significant mechanism for their specific biodistribution in tumor tissue. However, previous literatures mainly contributed with the use of different carriers and agents that encapsulate or form complex nanoparticles with the drug loading. Nevertheless, the drug loading capacity in the nanocarrier-based system is usually low and the presence of the carriers would increase the systemic toxicity of the drug formulation and their prolong degradation could be a potential health problem to the patient. Thus, we synthesized carrier-free, pure drug nanostructures to enhance the drug delivery efficacy without other agents or carriers. The results showed remarkable improvement for pure drug nanoparticles while comparing with the free drug. It is believed that the nanostructure of drug molecules enhance the endocytosis of the cell, leading to more drug nanoparticles uptake by the cells and caused cell death. Thirdly, we demonstrated high degree of surface roughness nanoparticles which enhanced cellular uptake than smooth surface nanoparticles. In the recent literatures, scientists revealed that surface roughness of nanoparticles can enhance the cellular uptake thus improving the drug delivery efficacy. Therefore, various methods to increase the surface roughness of nanoparticles with carriers such as mesoporous silica nanostructures were used. As we mentioned, carriers are not favorable in prolong degradation for patients, we synthesized a novel, pure drug nanostructures which by simple solvent exchange method and with high degree of surface roughness. It is first reported of such structure with entire pure drug composition only and we successfully demonstrated the enhanced cytotoxicity of high degree surface roughness nanoparticles comparing with the smooth nanoparticles. To conclude, we improved the efficacy rate of drug delivery by physical penetration of cell membrane by sharp diamond nanoneedles, allowing more drug molecules to enter the cell and cause cancer cell death. Furthermore, pure drug nanoparticles and nanorods were synthesized for enhancing the delivery rate by EPR effect. Moreover, pure drug nanostructures with high degree of surface roughness were demonstrated which promote cellular uptake of the drug particles, leading to rapid and effective drug delivery. All above methods shows promising result in boosting the drug delivery into the cancer cell. The strategy described could be useful and magnificent in the design and fabrication novel drug delivery methods.

Date of Award	3 Oct 2014
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Wenjun ZHANG (Supervisor) & Igor BELLO (Co-supervisor)