Catalytic-nanomedicine In Gbm Treatment

Tessy López Depto. de Atención a la Salud, Universidad Autónoma Metropolitana‐Xochimilco,  México. Laboratorio de Nanotecnología, Instituto Nacional de Neurología “MVS”, México.

C Cancer d fi i i definition Disease caused by normal cells changing so, that they growth in an uncontrolled way. The uncontrolled growth causes a lump called a tumor. 

Main characteristics of cancer cells  y self‐sufficiency y y y y y

in

growth signals insensitivity to anti anti‐ growth signals evasion of apoptosis li i l limitless replicative li i potential sustained angiogenesis tissue invasion and metastasis.

Mortality due to malignancy (México) 14 12 10 8 6 4 2 0 1922

1950

1980

1990

Fuente: http://www.dgepi.salud.gob.mx/

1998

1999

2001

Cancer Treatment Conventional off drug C ti l forms f d administration generally relyy on p pills,, eye y drops, p, ointments and intravenous solutions. But in the last few years we have witnessed an explosion in research aimed at creating new drug delivery systems.

Local Drug delivery Local application or direct tumor injection of p g has been p p chemotherapeutic drugs proposed as a method by which local drug concentrations can be maximized in the immediate tumor environment while systemic exposure and non‐target organ toxicity is minimized

9 Low L concentrations 9 toxic side effects

Platinum based drugs Platinum‐based drugs The interest in platinum‐based antitumor drugs has its origin in the 1960’s. Platinating agents have been extensively used as treatment in several types of cancer. A property common to many chemical carcinogens is that they are DNA reactive.

y Conventional platinum-based drugs are DNA reactive Pt-DNA adducts

Platinum complexes are now among the most widely used drugs for the treatment of  cancer. The search for improved platinum drugs continues with the h goals l off reducing d i the h toxic i side effects and broadening the spectrum of activity to tumours resistant to cisplatin.

Nanoparticles of biodegradable polymers may provide a solution for the problems in chemotherapy • sustained, controlled and targeted delivery; i.e. personalized chemotherapy; •delivery d l off therapeutic h agents across physiological drug barriers; •chemotherapy at home

Drugs may be bound in form of a solid solution or dispersion or be adsorbed to the surface or chemically h i ll attached. h d

l l Sol‐gel process y It is a suitable method for nanoparticles synthesis. synthesis y Because of a great variety of organic molecules  can be 

encapsulated into a inorganic matrix using sol–gel  p g g g process, it has gained considerable interest during the  past decade.

Hypothesis y A nanometric functionalized and biocompatible “ DNA‐

catalyst” (biocatalyst) with specific surface properties to  make possible its interaction at molecular level, with genetic  material of cancer cells , and capable to “break” some DNA  bonds (phosphodiesther, hydrogen bonds) and to induce an  apoptotic process, to avoid DNA replication in damaged  cells.

Nanometric particles y Due to their nanometric

size, our obtained  size  our obtained  biocatalysts are capable  to cross physiological  membranes (BBB,  celular, BSB, and so  forth)

UAM + INNN México

Nanotechnology Laboratory UAM-INNN

Our designed materials Our designed materials Pt/TiO2 and Pt/SiO2 nanoparticles, with: • High surface area •Surface acidity (Lewis acidity) • Well dispersed Pt (1%) over TiO2 or SiO2 nanoparticles surface •Stabilized Pt(II) species •High surface hydroxilation degree 2

% Tranmittance

Pt-SiO2-Piridina

1

B C D E 0 1700

1650

1600

1550

1500 -1

Wavenumber (cm )

1450

1400

Nanostructured biocatalysts for GBM treatment In vivo tests C6 cells inoculated in motor cortex and  treated by means of an implant formed by  the biocatalyst.

C6 cells inoculated intraperitoneally and  treated by means of an injection of  y j suspended nanopaticles. 

H‐E micrographs with Pt/SiO g p of  (a) tumor treated ( ) / 2‐Pt(NH ( 3)4Cl2 2 ,,  (b) 20X  y (c) TUNEL technique.

a

b

c

Particles

Titania

Platinum complex

60

Titania-Platinum

Tumoral weight reduction 24 6% 24.6%

50

Tumoral weigth (gr)

Control

43.4%

40

79%

*

30

20

10

0 CONTROL

Pt

TiO2

TiO2-Pt

*p=0.03 when compared with control

Average tumor size of C6 glioma in rats after treatment

Summary Su ay y Sol‐gel process is a suitable method to obtain

nanometric‐size particles with dispersed latinum atoms enhancing its catalytic activity.  activity   y A reduction of ca. 80% in tumor size was observed when the animals were treated with the biocatalyst. biocatalyst y Specific properties like high surface area, Lewis  acidityy , and nanometric p particle size make facilitates inteaction between DNA‐nanoparticles leading the cancer cell to an apoptotic process (no more  replication of damaged cells). cells)

y , p g y These novel biocatalysts, represent a good alternative for cancer treatment, specially when the tumor is located in  an inaccessible site.  y Besides, using Besides  using this local therapy secondary effects of  platinum can be totally eliminated and giving the patient a better quality of life.

C   @ di Contact: [email protected] www.labnano.hostmex.org