Cancer Drug Delivery Flashcards
Smaller particles are ___ at passing through to the tumors
better
The ideal shape for nanoparticles to pass into tumors via the bloodstream is:
Spherical
The ideal elasticity for particles trying to pass into tumors via the blood stream is
Soft molecules increase circulation/ targeting (less immune cell uptake)
How does hypertension (Incr BP) enhance the EPR effect?
Creates a larger volume of blood that flows into the tumor (more drug enters the tumor)
Why does increasing hypertension work to enhance the EPR effect?
Normal blood vessels have a layer of smooth muscle that regulates BP while tumors do not have this layer to regulate the flow into the tumor
How does hyperthermia (Incr Heat) enhance EPR effect?
Heat causes vessels to dilate which will lead to more drug entering the tumor
How does cell-mediated delivery enhance the EPR effect?
Cells release drugs that are specifically activated at the cancer sites, this increases the amount of drug that gets delivered into the tumor.
Active targeting selects targets that are _____ by cancer cells
overexpressed
methods to enhance EPR Effect
- Hypertension
- Hyperthermia
- Cell-mediated delivery
Ideal molecule to pass through into the tumor is a
small, spherical, soft particle
Targets for active targeting include
- Folate receptor
- Transferrin Receptor
- PSMA (Prostate-specific membrane antigen)
- Integrins
Integrins are known to bind to peptides W/ _____
RGD
Intrinsic stimulus is taking advantage of _____
tumor characteristics
Examples of responsive particles incude
- pH
-MMP’s - Heat
- Ultrasound
Why are tumors acidic?
They are hypoxic and produce lactic acid which drops the pH
Approximate pH of tumors
~6.5
What are MMPs?
matrix metalloproteinases
MMPs are ___ that cut proteins
enzymes
Each MMP cuts a _____ sequence
specific amino acid
MMPs are used to increase the ___ of drug in the tumor by cutting the amino acid sequence between ____ and the drug
concentration, PEG
What are CPPs?
Cell-penetrating peptides (cross membranes readily)
CPPs prefer to cross _____ as opposed to other membranes
cancer cell membranes
Ultrasound is applied ____ drug administration to facilitate _____
after, release/ activation
Five categories of immunotherapy
- checkpoint inhibitors
- CAR-T Cell Therapy
- Vaccines
- Antibodies
- Oncolytic Viruses
Characteristics of Antibodies as an immunotherapy
- naked
- possess ADC (antibody drug conjugate)
- Bispecific
Characteristics of vaccines as an immunotherapy
- Preventative
- therapeutic
How do checkpoint inhibitors work?
antibodies block cancer cell’s PD-L1 from binding with the PD-1 on T-cells
What happens when PD-L1 on tumor cells binds with PD-1 on T-cells?
It tells T-cells not to kill the tumor cells
Examples of checkpoint inhibitors?
- Keytruda
- Yervoy
What is CAR-T therapy?
T cells are removed from the body and CAR genes are inserted into the T-cells and CAR-T cells are grown and inserted into the patient which kills tumor cells
Examples of CAR-T Therapy
- Kymriah
- Yescarta
How do preventative cancer vaccines work?
Uses HPV virus to help prevent cervical cancer (sometimes throat canacer)
Examples of preventative cancer vaccines
- Gardasil
How do therapeutic vaccines work?
immune cellsa are collected and T cells are exposed to a protein that trains them to recognize the cancer cells and allows the patient’s cells to enhance the immune response. Cells are injected into the patient.
Example of therapeutic vaccine
Provenge
How do monoclonal antibodies work?
monoclonal antibodies interact with antigens on lymphoid and myeloid cells that induces a durable lymphopenia via a mediated system which is able to kill target cells.
Example of monoclonal antibodies
campath
Adcetris
Blincyto
how do oncolytic viruses work?
a modified virus (herpes) is injected into lesions and the virus multiplies in the lesions which triggers an imune response.
Example of oncolytic virus
imlygic
