Active targeting

Question 1

Active targeting

Answer 1

A ligand is attached at surface of a nanocarrier for binding to appropriate receptors at target site. The ligand may allow the drug to attach to the surface of cell or internalise for intracellular drug release. This formulation is known as Liganded PEGylated Nanoparticle.

Question 2

Aims of active targeting of cancer cells are:

Answer 2

• To improve cellular uptake of therapeutic macromolecular drugs
• To target surface receptor over-expressed by cancer cells only
• To target receptors that are likely to be internalised (such as EGFR)

Tumour endothelial cells (not cancer cells) can be targeted too; the aim is to destroy angiogenic blood vessels and kill tumour cells by depriving them of oxygen and nutrients.
 

Question 3

Radiotherapy

Answer 3

(AZ) Sy
A = atomic mass (p+n)
Z = proton number (also electron number)
Sy = element

Isobars are atoms of different elements having the same mass number (e.g. 6C14, 7N14, 8O14).
Isotones are atoms of different elements having the same number of neutrons (e.g. 14Si30, 15P31).

Question 4

Radioactive decay (Ionising radiation)

Answer 4

Nuclear instability is caused by the size imbalance of proton: neutron ratio. Two different isotopes of the same element will have different tendencies to undergo nuclear decay; carbon-14 (6 protons + 8 neutrons) is more likely to decay than carbon-12 (6 protons + 6 neutrons).
The strength of emission is measured in electron volts (eV), where the lethal dose is > 3 MeV

Question 5

Α decay (fusion)

Answer 5

o A nucleus breaks down, and a helium atom is released
o E.g. Ra → Rn + He2+ (helium atom – 2 protons & 2 neutrons)
o 1 α gives 10,000 atomic ionisations
o Most damaging to tissues, but least penetrating (µm) – dangerous when inside the body

Question 6

Beta decay

Answer 6

[, causing the release of a positron – an electron with a positive charge
o ß-particle (electron) – ß- decay
 A neutron suddenly changes into a proton, causing the release of an electron & neutrino
 E.g. K  Ca + e- + v
o 1 beta gives 100 atomic ionisations
o Damaging to tissues and penetrating (cm) – dangerous when outside the body

Question 7

Gamma decay

Answer 7

o The nucleus rearranges to a lower energy state, a photon (gamma ray) is released
o 1 gamma gives 1 atomic ionisations
o Very high energy & highly penetrating, causing DNA damage.

Question 8

Radioactive elements

Answer 8

Discovered by Marie Curie:
Uranium – █(238@92) U is the most abundant isotope (99.27%) and is a natural α emitter
Radium – 223Ra is a radiopharmaceutical produced from the decay of 235U
Polonium – 210Po is a powerful α emitter, 1 million times more toxic than cyanide

Question 9

Useful radioactive elements

Answer 9

Element	Half-life	Use
Gallium , 68Ga	68 min	Imaging
Rubidium, 81Rb	4.7 h	
Molybdenum, 99Mo	66 h	 Moly-Cow (used to extract 99mTc)
Polonium, 210Po	180 day	
Germanium, 68Ge	280 day	
Cobalt, 60Co	5 years	Sterilisation

Question 10

Applications- Radiotherapy (RTX)

Answer 10

Most radiotherapy treatment is given by External Beam Radiation Therapy (EBRT). Tumours with a diameter of ≥2 cm can be treated using EBRT.
63% of patients diagnosed with breast cancer have radiotherapy as part of their primary cancer treatment. RTX is recommended after a lumpectomy. The survival rate of BRCA is increased by 32-67% with the use of radiotherapy.

Question 11

Radiotherapy involves daily treatments for 6/7 days over 6 weeks

Answer 11

Dosing regimens (Gy/hour):
•	Low dose rate (LDR): <2
•	Moderate dose rate (MDR): 2-12
•	High dose rate (HDR): >12

Question 12

APBI is Accelerated Partial Breast Irradiation and interstitial RTX. The subtypes are:

Answer 12

• IMRT – Intensity modulated radiotherapy (IMRT)
• IBRT – Internal Beam Radiotherapy (internal mammary radiotherapy)
o the insertion of radioactive implants (platinum, iridium, indium and palladium) directly into tissue
o Often used for large and capsulated soft tissue tumours
• IORT – intraoperative radiotherapy

Question 13

Radiolysis of water produces hydrogen and hydroxy ions and hydrogen and hydroxy free radicals: water:

Answer 13

: H+ + HO- + H• + HO•. Additional contact with nearby oxygen creates super-oxides, which cause damage to the cell (indirect DNA damage). These destroy DNA by breaking double strands, leading to cell death. If a tumour is anorexic, it is deprived of oxygen due to rapid outgrowth of blood supply, therefore fewer superoxide are produced; solid tumours are very anorexic and are radio-resistant above 0.5cm3.
Fractionation is where the total dose of radiation is divided into several, smaller doses over a period of several days. This reduces the toxic effects on health cells.

Question 14

Main goals of RTX:

Answer 14

Repair:
o Although non-cancerous cells may be affected, their ability to heal double-strand breaks is better than cancer cells
o Fractionation allows normal cells to repair

Question 15

Repopulation

Answer 15

o Tumour cells can repopulate when incompletely damaged
o Each fraction (dose of radiation) must cause more damage than the cells ability to repopulate
o Fractionation allows normal cells to repopulate

Question 16

Re-assortment

Answer 16

o Each fraction allows re-assortment of tumour cells to be in the M-phase
o More considerable DNA damage is caused

Question 17

Reoxygenation

Answer 17

o Most DNA damage is indirect (caused by super-oxides due to free radical contact with oxygen)
o Fractionation causes oxygen-rich tumour cells to die first, and previously hypoxic tumour cells to become oxygenated
o Cells are more susceptible to radiation in next fraction.

Question 18

Exposure to radiation has many effects, including:

Answer 18

fatigue, fever, vomiting & nausea (from first exposure), white blood cell damage (after 7 days), hair loss (after 12 days). Other effects include abdominal pain, palpitations, promotion of cancer, and organ damage.