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Homework #1

Nanomedicine: BIOEN 6405/PHCEU 7230, Fall Semester 2017


Due in class on Tuesday October 3rd
Total # of points possible: 100

1. Defining the nanomedicine:


a. What is a nanoparticle? (1 pts)
Particles with lengths between 1 nm to 100nm size in any two -three dimensions.

b. What is nanomedicine? (2 pts)


Nanomedicine is use of nanobiotechnology in medicine as a imaging agent and
diagnostics in our body, real-time assessment to accelerate clinical translation,
monitoring predictive molecular changes of Nano particle during interactions with
cells or blood, making of multifunctional nanoparticles as drugs Etc.

c. FDA approved nanomedicines:


i. Describe the key features of one nanomedicine formulation approved by
the US FDA that we have discussed in class or mentioned on the lecture
slides? (4 pts)
Abraxane: is Nano particle(drug) which has outer shell of Albumin. This
Albumin activate GP-60 receptor on vascular endothelial cells and interact
with caveola one protein leading to formation caveola and reach to tumor
and release the drug.

- The key feature is drug trapped inside Albumin shell.


- Easy transport due to its Nano size
- It uses tumor mechanism to get nutrients against itself.
- Like Tumor usage of GP60 pathway

ii. What are the advantages and disadvantages of the nanomedicine


formulation compared to the small molecule drug formulation? (4 pts)
Advantages :
-Drug delivery to the more accurate location so less or no intake by other
cells.
-Detection and imaging is easy and more accurate.
-more surface area on drugs

Disadvantages :
-High cost of nano drugs
-Nano particles may have different properties for an example
amalgamation of some particles may result in complete different
properties of that particle than all other individual particles.
-

2. Identify a nanoparticle of interesting shape, configuration, or function from primary


literature that is being investigated for a nanomedicine application and:

a. Provide the full literature reference for the nanoparticle you chose. (1 pt)
Yu, T.; Malugin, A.; Hamidreza, G. Impact of Silica Nanoparticle Design on
Cellular Toxicity and Hemolytic Activity. Am. Chem. Soc. 2011, 5(7), 57175728.

b. Describe the nan1oparticle size, shape, chemical composition (illustrations are


recommended). (3 pts)
(Silica Nanoparticles) Size and shape:

A-Silica Nano sphere(115nm) (A in figure)


B and F-mesoporous silica Nano sphere(120nm):
C,D,E-mesoporous silica nanorods (w*L= 80 x 200, 150 x 600, 130*1000nm,
AR: 2,4,8 respectively)

Produce cation charge is produce on surface by amine silane groups.


c. Why is this particle interesting as a potential nanomedicine? (2 pts)
Silica Nano particle has large surface area, controllable particle size, controllable
shape and biocompatibility made this particle good carrier for drugs.

d. Describe the synthesis of the particle including reagents used? (2 pts)


mesoporous SiO2 was formed by condensation under dilute silica source (Tetra methyl
Orth silicates (TMOS)) and low surfactant concentration conditions with ammonium
hydroxide as the base catalyst with reaction agents (cetyltrimethylammonium chloride).

By changing the concentration of tetraethyl orthosilicate (TEOS),


cetyltrimethylammonium bromide (CTAB), and aqueous ammonia and reaction stirring
rate, mesoporous SiO2 with targeted diameters (ca. 100 nm), lengths, and aspect ratios
(1, 2, 4, 8) were synthesized.

e. Particle Characterization:
i. How was the particle characterized? (3 pts)
Particles are characterized by TEM imagining (For different shape and
sizes), Nitrogen adsorption and desorption isotherms for different shapes.
Dynamic Light scattering for size distribution profile and zeta potential
measurement for surface charge density.

ii. What additional tests/experiments would you perform to characterize the


particles? (2 pts)
Optical Spectroscopy to determine (confirming) size of nano sphere.
Mass spectroscopy to check purity of Nano particle.
SEM for surface roughness.
3. Lithography
a. Define lithography? (2 pts)
Lithography is processing to modify flat surface according to our use with
different method like etch, grow, drop, lift off.
b. How can the diffraction limit of light be overcome to create nanoscale features
using lithography? (3 pts)
Absorbance modulation: use of 2 types of wave lengths. One wavelength makes
surface opaque and other one makes surface transparent. By imposing those two
wavelength lights makes Nano scale probe at the surface.

By increasing, opaque light power density reduces the lights spot size, gives
narrower light beam.
c. Identify from primary literature at least one use of lithography in nanomedicine
i. Provide the full literature reference(s). (1 pts)

Jie-Ren Li, Kathie L. Lusker, Jing-Jiang Yu and Jayne C. Garno;


Engineering the Spatial Selectivity of Surfaces at the Nanoscale Using
Particle Lithography Combined with Vapor Deposition of Organosilanes
;Am. Chem. Soc. 2009, 3(7), 2023-2035.

ii. Describe the application as it relates to nanomedicine. (3 pts)


In nanomedicine, surface area and size of Nano particle greatly effect on
cell intake, toxicity of particle. By lithography, we can develop minimum
variation in nano particles and Lithography is cheaper mass production.
-We can make complex shapes of nanoparticles by lithography.
-We can use lithography concept to modify the surface properties of
particles

4. Synthesis and characterization of inorganic nanoparticles


a. List and describe the 4 key characteristics of precipitation based synthesis of
inorganic nanoparticles. (4 pts)
-The products are generally insoluble spices formed under condition of high
saturation
-A large number off small particle are formed due to nucleation
-secondary processes like Ostwald ripening and aggregation, dramatically affect
the size, morphology and properties of products
-The supersaturation condition necessary to induce precipitation are usually the
result of the chemical reaction.
b. What is the mechanism of Ostwald Ripening? (2 pts)
Ostwald ripening is an observed phenomenon in solutions that describes the
change of an inhomogeneous structure over time. Smaller particle diffuses in the
solution due to higher solubility and larger particle precipate.

c. How can organic compounds be used to create porous inorganic nanoparticles? (2


pts)
Coat of inorganic particle on the organic compound and remove inner organic
compound by solvation or calcination.

d. Assume you have just synthesized a new batch of PEGylated iron oxide
nanoparticles. Describe the tests you would use to characterize the particle
hydrodynamic radius, size of the polymer corona, size of the iron oxide core,
chemical composition/purity, and magnetic properties? (5 pts)
Hydrodynamic radius: Dynamic light scattering
Size of polymer corona: Infrared spectroscopy, EDS, XPS
Size of iron oxide cores: TEM
Chemical composition/ purity: Mass spectroscopy
Magnetic Properties: Zeta potential mesurement
5. Creation of Polymeric Materials:
a. Given the monomer with the structure of CH2=CHS (where S is a substituent)
i. Describe the steps involved in free radical polymerization of the
compound. Include the formula scheme(s) in each step. (4 pts)

Attached solution (Last page)

ii. List 3 types of polymers that are synthesized by free radical


polymerization. (2pts)
Polystyrene, Poly(methyl methacrylate), Polyvinyl acetate

b. Given an equal mixture of monomers capable of step-growth (condensation)


polymerization A= NH2-R-NH2 and B= HOOC-R-OOH (R indicates a
hydrocarbon chain of any particular length):
i. Describe the stages involved in step-growth (condensation)
polymerization of the compound. Include the formula scheme(s) in each
step. (3 pts)
Attached solution (Last page)

ii. What would be the co-polymer arrangement for the combination of


monomers A & B?(2 pt)
Attached solution (Last page)

iii. List 3 types of polymers that are synthesized by step-growth


polymerization. (2 pts)
Polyester, Polyamide, Cellulose

c. Describe RAFTs and ATRP and how they differ from other types of
polymerization. Include a reaction scheme in each case. (4 pts)
Attached solution (Last page)

6. What are the advantages and disadvantages of in vitro vs in vivo testing for nanoparticle
toxicology (the creation of a table is recommended)? (6 pts)
7. Cellular uptake of Nanoparticles
a. Describe the various cellular uptake mechanisms and include schematic diagrams.
(5 pts)u
b. How does ____ influence particle uptake?
i. Size (2 pts)
ii. Geometry (2 pts)
iii. Porosity (2 pts)
iv. Surface chemistry (2 pts)
8. Influence of the protein corona on nanomaterials
a. What is the protein corona and why is it an important consideration for
nanomedicine both for in vitro and in vivo? (3 pts)
b. What factors influence the composition and thickness of the protein corona on a
nanoparticle? (2 pts)
9. Carmeda AB is a company that produces nanoscale coatings to improve the blood
compatibility of various medical devices. Look up information online about the
CARMEDA Bioactive Surface online and answer the following questions.
a. What is this coating made from and how is it synthesized? (2 pts)
b. How does this coating work to prevent/reduce thrombosis? (3 pts)
c. What specific blood components are targeted in its function? (2 pts)
d. Why might this strategy function effectively under only certain blood exposure
conditions? (3 pts)
e. Would you expect the effectiveness of this coating to differ between venous and
arterial flows? Please, justify your answer. (3 pts)