exam 4- cancer 2

Question 1

active drug in doxil is doxorubicin, which produces ___

Answer 1

doxorubicin, ahthracyclines, produce Streptomyces bacteria

Question 2

doxorubicin acts on the nucleic acids of dividing cells by 2 main mechanisms of action:

Answer 2

1- it inhibits DNA & RNA synthesis by intercalating b/w base pairs of the DNA strands, thus preventing replication and transcription in rapidly-growing cancer cells

2- it inhibits the enzyme topoisomerase II, preventing the relaxing of supercoiled DNA (an additional way for blocking DNA replication & transcription)

Question 3

targeting motif in doxil: active targeting

to achieve active targeting of cancer sites, a variety of ___ are utilized to exploit any specific antigens expressed by cancer cells (peptides, antibodies, proteins…)

breast cancer is characterized by a high expression of estrogen receptors including ___, ___, and ___, which can be targeted actively by ____

EndoTag-1 (proprietary formulation design for beast cancer, derivate from ___

Answer 3

ligands

MAPK, HER2/neu, and epidermal growth factor receptor , EGFR/VEGFR

• the amt and type of receptors varies b/w patients with the same cancer (based on their biomarkers)

modified liposomes

doxil

Question 4

targeting motifs in doxil: passive targeting

the basis for the passive targeting =

increased ___ in the affected tissues with a much lesser return of fluids to ___ circulation

in this way, drugs encapsulated in liposomes…

Answer 4

tighter structures found in normal capillaries vs. cancer capillaries

enhanced permeability & retention effect

blood capillary permeability
lymphatic

up to 400 nm, can be accumulated efficiently in tumor sites

Question 5

how to avoid rapid clearance of NPs by MPS (prolonged circulation time)

Answer 5

1- surface modification (conjugation of PEG)
2- surface charge (neutral NPs have decreased rate of MPS uptake)
3- size (mean diameter of 100 nm have prolonged circ)

Question 6

does doxil fit all the criteria needed for prolonged circulation time?

Answer 6

yes

Question 7

upon intravenous administration, NPs passively accumulate in ___ sites; at the same time, their nanosized or specific cancer ligands prevents them from accumulating in ___

how can we study biodistribution with non-invasive methods?

Answer 7

tumor
healthy tissues

imaging

Question 8

why label NPs with radioisotopes and NIR fluorescent dyes?

radioisotopes are same element with equal number of ___ but diff numbers of ___ in the nuclei- their nuclei are ___, so they ___ and emit ___

Answer 8

protons, diff neutrons

unstable, break down/decay, emit radiation

can be detected in minimal amount by diff devices

Question 9

why label NPs with radioisotopes and NIR fluorescent dyes?

NIR wavelengths b/w ___ and ___ are advantageous in vivo because of the ___ of biological molecules in this region

Answer 9

700-900 nm

low absorption

deep penetration in tissues (photon penetration)
- reduces the use of radioactivity

Question 10

optical imaging methods to study nanomedicine biodistribution

Answer 10

1. Positron Emission Tomography (PET) - mostly used in humans (radioisotopes)
2. Optical Imaging - mostly used in animal models (IR-dyes)
   2D fluorescence imaging (FI)
   3D fluorescence molecular tomography (3D-FTM)
   PET-optical dual-modality imaging

Question 11

PET is based on the detection of radioactivity emitted after a ___ is injected into a peripheral vein

technique that measures ___ by looking at ___

PET can be used to track ___ and __-

Answer 11

small amt of a radioactive tracer

physiological function by looking at blow flow

radiolabeled-NPs and tumors

Question 12

Optical imaging (OI) is in vivo imaging with ___ and ___ agents

detection: special devices designed for ___ detection, they can be coupled with classic structural imaging systems (xrays, CT, MRI)

Answer 12

near-infrared and contrast agents

fluorescence

Question 13

PET-optical dual-modality imaging is imaging of ___ or ___

Answer 13

NIR dyes or radioisotopes