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Cancer
• Historically agents given systemically
– Agents that kill rapidly dividing cells
• Find therapeutic dose  Kills tumor cells w/o
killing patient
– Lots of side effects
• Localized/targeted delivery is the holy grail
– Nanomedicine!!
– Also protection from degradation and increased
solubility
• Nanoparticles –
drug throughout
• Nanocapsules –
drug w/in coating
• PEGylation – makes
stealthy
• Ligand – binds to
cell receptor for
targeting
Tumor Vasculature
• Irregularly shaped, big, and leaky
• Lack of lymph drainage
• High vessel density
Passive Targeting  EPR
• Small drugs enter tumor and leave
• Particles enter and stay
– Long circulation time key
Active Targeting
• EPR + something that binds tumor cells
specifically
Targeting
 depends upon over-expression of
surface molecules by tumor cells
 Interfere with signaling when
bind (targeting ligand and drug)
 Ab tethered to drug
 Ligand + drug
Paige
Paige
Daruwalla, Cancer Science,
2010; 101; 1866-1874
MoCR
IC50=1.2 mM
HT-29
IC50=0.85 mM
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Paige
DLD-1
IC50=0.8 mM
MCF-7
IC50=0.8 mM
Shrinidhi
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Shrinidhi
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Shrinidhi
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Anna
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Anna
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Anna
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Felix
Daruwalla, Cancer Science,
2010; 101; 1866-1874
Kevin
Kevin
Lehtinen, PLOS One, 2012;
7(7); e41410-
Inseong
Lehtinen, PLOS One, 2012;
7(7); e41410-
Inseong
Lehtinen, PLOS One, 2012;
7(7); e41410-
Maura
background
non-targeted
pre-targeted
direct target
Lehtinen, PLOS One, 2012;
7(7); e41410-
Maura
Lehtinen, PLOS
One, 2012;
7(7); e41410
Michael
Lehtinen, PLOS One, 2012;
7(7); e41410-