Nanoparticle Therapies

By Julio Francisco, Roshanak

Gonzalez, Christian Rydstrand,
and Ryan McCully
 Lesson Objectives
● Define “Nanoparticle” and “Nanoparticle Therapy”
● Introduce Nanoparticle Background & History
● Motivation / Goals / Problems Solved / Applications
● Introduce Studies Performed
● Specific Experiments Elaboration
○ VEGF Mechanism & Inhibition By Antibodies Inhibitors
○ Gold, Silver, and Iron Nanoparticle EGF Inhibition
○ Antiangiogenic Properties of Silver Nanoparticles
○ Therapeutic Effect of Aloe Vera and Silver Nanoparticles
● Future Applications
● Conclusions
● Q/A
 Nanoparticle
Definition:

A microscopic
particle that's
between 1 and 100
nm in diameter
 Nanoparticle Inhibition
Definition:

Nanoparticles have the

ability to inhibit
(block/prevent)
enzymes involved in
controlling cellular
processes
 Nanoparticles and Regeneration
Nanoparticles can be used to enhance
the recovery of injuries. They can be
used to reduce inflammation and
improve fibroblast function.

Nanoparticles can also be used to create

scaffolds that can enhance bone growth
or elicit a wanted response.[5]
Motivation of NP Inhibitor Research
● Low cost and high efficiency in many aspects of medicine
● Small size able to reach target cells more easily
● Applications include:
○ Cancer treatment (cell growth, migration, proliferation, and receptor expression)
○ Imaging
○ Controlled wound healing and recovery (ability to fight infection and inflammation)
○ Tool for drug delivery
○ Possess antimicrobial, antifungal, and antiviral properties
● Novel avenue for research and a lot of potential for broad ranges of
application
 History of VEGF Inhibitors

Nucleotide-Based

http://slideplayer.com/slide/10276813/
VEGF Mechanism & Inhibition By Antibodies Inhibitors

H. Goel and A. Mercurio, "VEGF targets the tumour cell," Nature Reviews Cancer, vol. 13, pp. pages 871–882, 2013.
Synthesizing Nanoparticle VEGF-inhibitors

Schematic
Design

TEM
Image
Quartz Crystal Microbalance (QCM) used to
evaluate NP affinity to VEGF

https://www.sciencedirect.com/science/article/pii/S1876162315000486
 Nanoparticles Results
VEGF
NP4
NP2
NP3 No significant Bind Effect

NP2-4 contained negatively charged sulfonate group

NP5 NP6 NP7 NP8

Mix Results

NP9
NP10

NP5-10 containing the 3S-GlcNAc, 4S-

GlcNAc or 6S-GlcNAc

Mix Results
NP11
` NP12 NP13

NP11-13 contain tri-sulfated GlcNAc monomers

Result
Results
Does N11 inhibits VEGF from bind to VEGFR-2?
Western Blotting
Mechanism of Inhibition
 Inhibition of VEGF-dependent activities

VEGF165-dependent
cell motility

VEGF165-dependent
capillary tube
formation

https://www.promocell.com/blog/understanding-vasculature-help-
huvecs/
 Nanoparticles Used*

Experiment: Nanoparticle EGF Inhibition ●

●
●
Silver (Ag-NP)
Gold (Au-NP)
Iron Oxide (SPION)

Objective: Examine the effects of Metallic Nanomaterials on Epidermal

Growth Factor (EGF) within the human epithelial cell line.

Hypothesis: Does Ag-NP, Au-NP, and SPION have any biological influence
on EGF association, Akt/Erk phosphorylation, Akt activity and EGF-
dependent gene regulation?

EGF: A mitogenic
protein involved
in cellular
proliferation,
differentiation,
and survival.
 EGF Inhibition Continued..
Materials and Methods: Human epithelial cell line A-431 was
dosed with Au-NP, Ag-NP, SPION at a concentration of 15 μg/mL
then evaluated following 24 hours exposure (elution process).

Results: The introduction of gold, silver and iron nanoparticles

were all shown to impair the A-431 cell line response to EGF in
their own specific mechanism of alteration. EGF Receptor
Pathway

Significance: Could potentially be used in the

development of therapeutics targeting cancer and
inflammation.

Limitations: Difficulty extrapolating results to

an in vivo system using an in vitro model. TEM images of (A) control
A-431 cells following 24-h
exposure to (B) Ag-NPs, (C)
Au-NPs, and (D) SPIONs.
Research: Antiangiogenic Properties of Silver Nanoparticles
Objective: Investigate the use of silver nanoparticles (Ag-NPs) as anti-
angiogenic treatment and compare to current treatments

Hypothesis: Ag-NPs might have ability to inhibit angiogenesis by inhibiting

activation of PI3K/Akt.
● Cell proliferation
● Migration
● Capillary-like
tube formation
● In vivo
angiogenesis Source: https://www.indiamart.com/proddetail/silver-nanoparticles-
14415749973.html
Cont…
Materials and Methods: Cell cultures with BRECs were treated with VEGF and Ag-
NP or VEGF and PEDF (positive control), and incubated for 24 hours.

Assays done for matrigel plug (in vivo angiogenesis), migration, tube formation,
endothelial cell viability, and cell proliferation

Results: Ag-NP were as effective as an anti-angiogenic as PEDF in all steps of

angiogenesis tested in this study

Significance: Better treatment of eye-related neovascular diseases and better

understanding of NPs role in influencing cell processes
In vovo mitrigel plug assay; Sourced from [3]

Ag-NP or PEDF inhibit VEGF-induced migration of

endothelial cells; Sourced from: [3]

In vivo rat model with mitrigel implant; sourced

from [3]
Therapeutic Effect of Aloe Vera and Silver Nanoparticles
Objective: Research effect of Silver Nanoparticles and aloe vera on oral ulcers
induced by gamma radiation.

Hypothesis: Silver Nanoparticles used with aloe vera will increase wound
healing.

Methods: Several groups of mice were split into groups with varying
treatments. There was a control group which receives no treatment, group
with induced ulcers, an only aloe group, an only silver group, and finally a
silver and aloe group. [6]
Regenerative Properties
Silver nanoparticles were used with
Aloevera to increase contractility of
Fibroblasts and myofibroblasts. This was
done by increasing the expression of α-
SMA. [6]
 Future Direction
Nanoparticles have many versatile properties that can be applied in almost every aspect of
medicine. There are a wide range of types such as liposomes, albumin bound, polymeric,
iron oxides, quantum dot, and gold. These can all be used for things such as drug delivery,
imaging and sensing. The nanoparticles are readily available and are relatively low in cost.
 References
OUTLINE FOR PRESENTATION
[1] Hiroyuki Koide et. al., "A polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF165). " Nature
Chemistry, vol. 9, pp. 715-722, 2017.

[2] Comfort, K., Maurer, E., Braydich-Stolle, L. and Hussain, S. (2011). Interference of Silver, Gold, and Iron Oxide Nanoparticles on
Epidermal Growth Factor Signal Transduction in Epithelial Cells. ACS Nano, 5(12), pp.10000-10008.

[3] Gurunathan, S., Lee, K., Kalishwaralal, K., Sheikpranbabu, S., Vaidyanathan, R. and Eom, S. (2018). Antiangiogenic properties of
silver nanoparticles. [ebook] Elsevier, pp.6341–6350. Available at:
http://file:///C:/Users/ROSHIE1234/Downloads/Roshie's%20PR%20article.pdf [Accessed 9 Apr. 2018].

[4 ] E. SF, "Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice. - PubMed -
NCBI", Ncbi.nlm.nih.gov, 2018. [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/29412224. [Accessed: 09- Apr- 2018].

[5]Rijt, Sabine van, and Pamela Habibovic. Journal of the Royal Society Interface, The Royal Society, Apr. 2017,
www.ncbi.nlm.nih.gov/pmc/articles/PMC5414913/.

[6] Therapeutic Effect Of Aloe Vera and Silver Nanoparticles on Acid-induced Oral Ulcer in Gamma-irradiated Mice.
A El-Batal-S Ahmed - https://www.ncbi.nlm.nih.gov/pubmed/29412224
1) What are nanoparticles role in biological inhibition/promotion?
2) The higher levels of ______ will lead to higher ________.
3) Which test group recovered the best?
a) Aloe Vera and silver
b) Aloe Vera only
c) Silver only
d) No treatment
4) True or False: Silver nanoparticles are the only metallic nanoparticles to be tested in medical settings