טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentZoaby Nour
SubjectAutonomous, Self-destructing, Nanoswimmers for Cancer
Therapy
DepartmentDepartment of Chemical Engineering
Supervisor Professor Avi Schroeder
Full Thesis textFull thesis text - English Version


Abstract

Liposomes are vesicles composed of lipids, with an inner aqueous core and external membrane. Though liposomes are promising drug delivery systems for treating diseases in general and cancer in particular, they still lack an autonomous navigation system towards diseased tissue.

We sought to develop a smart navigation system that can perform complex maneuvers while utilizing available energy sources from its environment. Bacterium meets this requirement; it is self-propelled, motile, and uses energy from the surrounding. Bacteria sense the environment and, in accordance, proceed towards specific sites and invade them. Moreover, the ability of bacteria to suppress cancer has been known since the 19th century.

Bacteria penetrate tumors, while the drug alone has limited accessibility. Bacteria was shown to invade breast cancer cells in high ratio of 30% as shown in our confocal microscopy images.

The purpose of the study and one of its challenges is using bacteria as a vivid and live “submarine”. Specifically, a self destructing submarine, loaded with a drug. For this purpose, we developed a method for loading therapeutic liposomes into bacteria with high efficiency and low damage, based on weakening its membrane to make it more permeable. The charge of the loaded liposome, whether it is positive or negative, plays an important role in the viability of these bacteria, confirmed by confocal microscopy images and growth rate.

Doxorubicin, an anti-cancer and anti-bacterial drug, was charged into the liposomes, and these, in turn, were loaded into the bacteria. Once the drug performs its antibacterial activity on the bacterial body, the extra drug molecules are released from the damaged and perforated bacterial body to execute the anticancer activity on the cancerous cells. This activity was tested on Salmonella, the effectiveness is expressed on a severe damage on bacteria; SEM images show changes in morphology and topography, while a remarked decrease in their growth was obtained by counting technique.

This system is based on bacteria and doxorubicin and called briefly BADOX. which showed the lowest cancer cell viability in comparison to bacteria alone and free drug.

In summary, we developed a nanoswimmer that carries a nano-drug towards cancer cells. Our approach is simple and versatile. The nanoswimmer that carries the liposomes consumes energy from the rich nutrient surrounding in the tumor area. The system has proved effectiveness in targeting and killing tumor cells. This is the first proof of the ability to load liposomes in bacteria, and is a new platform to carry targeted drugs.