1. Nanotechnology for Therapy
BIOE298DP

2. Source: Comprehensive Cancer Center Ohio University
Drug Delivery
Because of their small sizes, nanoparticles are taken by cells where large particles would be excluded or cleared from the body 1
A nanoparticle carries the pharmaceutical agent inside its core, while its shell is functionalized with a ‘binding’ agent
Through the ‘binding’ agent, the ‘targeted’ nanoparticle recognizes the target cell. The functionalized nanoparticle shell interacts with the cell membrane
The nanoparticle is ingested inside the cell, and interacts with the biomolecules inside the cell
The nanoparticle particles breaks, and the pharmaceutical agent is released 2 3 4
Source: Comprehensive Cancer Center Ohio University

3. Revisiting the Importance of Size in Distributive Properties of Probes

4. A Drug Delivery Nanoparticle
Nanoparticles for drug delivery can be metal-, polymer-, or lipid-based. Below (left) an example of the latter, containing SiRNA encapsulated, and functionalized with an specific antibody. SiRNA can control often lethal inflammatory body responses, as shown in the microscopic images below (right)
antibody
lipid
SiRNA
Healthy tissue
Sick tissue treated with non-targeted nanoparticles
Science 2008, Vol. 316, pp
Sick tissue treated with targeted nanoparticles

5. Clinical Example of EPR
Doxil is a polyethylene glycol coated liposomal formulation of doxorubicin.
Marketed by Ben Venue Laboratories  of J&J. Outside the US, Doxil is known as Caelyx (Janssen).
Approved by the FDA for treatment of ovarian cancer and multiple myeloma and an AIDS-related cancer.

6. Example of an Approved Anticancer Agent
Protein-bound paclitaxel is an injectable formulation of paclitaxel, a mitotic inhibitor drug used in the treatment of breast cancer, lung cancer and pancreatic cancer.
Paclitaxel
Albumin

7. Targeted Nanoparticle
A dual Nanoparticle, the targeting ligand allow it to diagnose if a cell is healthy or sick, and bind specifically to the tumorous cell
Once inside the cell, the polymeric nanoparticle degrades and the anticancer agent is set free
Annu. Rev. Biomed. Eng Vol. 9, pp. 257–88
An imaging agent can be added as well
Imaging
agent

8. The pH stimuli sensitive systems
The pH of the pathological tissue is lower than the normal tissue, e.g. at the site of inflammation pH drops from 7.4 to pH 6.5. The same is observed in the case of infarcts.
Also, the pH is lower in the tumor mass (pH 6.5) than the surrounding tissue (pH 7.4).
The microenvironment of a tumor is acidic because insufficient oxygen in tumors leads to hypoxia and causes production of lactic acid. 

10. pH Sensitive NanoCarrier As a Theranostic Platform
AuNPs for cancer imaging (A) enzyme sensitive AuNPs for NIRF imaging, (B) tumor targeting: AuNPs for NIRF/CT dual imaging, and (C) schematic illustration of PEGylated for theranosis.

11. Ultrasound Mediated Therapy
Subcutaneously implanted rat prostate carcinomas seven minutes after administration of unspecific microbubbles (L) and RGD-coated microbubbles (R)

12. Nanotubes
Carbon nanotubes have been found to have a very interesting property, they release heat when exposed to radio frequencies
Chemical properties of nanotubes allow them to be easily functionalized
For this studies the nanotubes were produced by the CoMoCAT procedure, and functionalized with the polymer Kentera
Source:
CoMoCAT nanoparticles with grown nanotubes
Source: Southwest nanotechnologies

13. Source:Hamamatsu Nanotechnology
Heat Release Tests
Suspensions of nanotubes at different concentrations were remotely irradiated with radio waves, resulting in heating correlated to the concentration of nanotubes in suspension
250mg/L
50mg/L
0mg/L
Radiowaves
Nanotube suspension
Source:Hamamatsu Nanotechnology
Cancer 2007;Vol.110, pp. 2654–2665

14. Cytotoxicity tests
The following human cells were grown with 24h contact with 500mg/L nanotube solutions:
Hepatocellular carcinoma Hep3B
Hepatocellular carcinoma HepG2
Panc-1 pancreatic adenocarsinoma
The results shown correspond to fluorescence cytometric results, the segments represent stages of cellular growth, which appear unaltered despite the presence of the nanotubes. NO CYTOTOXICITY
Cancer 2007;Vol.110, pp. 2654–2665

15. Intracellular Accumulation of Nanotubes
Despite the lack of cytotoxicity, bright field images clearly shows the accumulation of nanotube structure inside the cellular structure
nanotubes
Culture without SWCNT’s
Culture with SWCNT’s
Also, the optical response of the cultures to other imaging techniques is shown by this IR image
Cancer 2007;Vol.110, pp. 2654–2665

16. In Vivo cytotoxicity test
In the top panel, the photomicrograph of
a hepatic tumor on a rabbit.
The black stains correspond to nanotube
accumulation on the tumorous cell
The purple staining is characteristic of
live tissues
In the bottom panel, the photomicrograph of
the same hepatic tumor after 2 min. radio
frequency waves irradiation.
The brownish color is indicative of necrosis
(tissue death)
Cancer 2007;Vol.110, pp. 2654–2665

17. Therapy w/o Any Chemotherapeutics
Nanometer-sized particles are particularly responsive to electromagnetic and acoustic excitations through a variety of phenomena (e.g. plasmon resonance) that lead to local extreme conditions (e.g. heating). The nanoparticle is able to tolerate this condition, but no so the biological material nearby
Intramuscular injections of colloidal gold, a suspension of gold nanoparticles, has been used for decades to alleviate pain linked to rheumatoid arthritis. The mechanism is still unknown
An infrared beam illuminates two mice specimens. The local temperature increases for the mouse that received and injection of gold nanorods.
Source: John Hopkins Center
Colloidal gold
Source:
Adv. Mater. 2009, 21, 3175–3180

18. Tackling Alzheimer Disease
Source: Berkeley Lab
Alzheimer and other degenerative diseases are caused my the clustering of amyloidal beta (Aβ) protein.
Alzheimer’s brain
Healthy brain
Gold nanoparticles can be functionalized to specifically attach to aggregates of this protein (amyloidosis)
Functionalized nanoparticle
Chemical structure of Aβ-protein
Source: wwwthefutureofthings.com
Source:

19. Gold Nanoparticles vs. Alzheimer
The functionalized gold nanoparticles selectively attach to the aggregate of amyloidal protein. The microwaves of certain frequency are irradiated on the sample.
Resonance with the gold nanoparticles increases the local temperature and destroy the aggregate
Before irradiation
After irradiation
Nanoletters 2006, Vol. 6, pp