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

Interfere with signaling when bind (targeting ligand and drug)

Ab tethered to drug

Ligand + drug

depends upon over-expression of surface molecules by tumor cells

Paige

Daruwalla, Cancer Science, 2010; 101; 1866-1874

Paige

Daruwalla, Cancer Science, 2010; 101; 1866-1874

MoCRIC50=1.2 mM

MCF-7 IC50=0.8 mM

HT-29IC50=0.85 mM

DLD-1IC50=0.8 mM

Paige

Daruwalla, Cancer Science, 2010; 101; 1866-1874

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

Kevin

Lehtinen, PLOS One, 2012; 7(7); e41410-

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

backgroundnon-targetedpre-targeteddirect target

Lehtinen, PLOS One, 2012; 7(7); e41410

Maura

Lehtinen, PLOS One, 2012; 7(7); e41410-

Michael