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Design of Cancer-TargetingTherapeutic MicellesEneida ChesnutChemical Engineering MajorSanta Barbara City CollegeINSET/CNSI ProgramMentor: Brian LinMatt Tirrell’s s Research Group

An Alternative Delivery SystemFor Cancer Therapy‣ Chemotherapy is highly toxic‣ Currently research is developing more effective waysto deliver therapeutics‣ Our Approach‣ Molecules that are able to target tumor cells‣ Synthesis of peptide-amphiphiles that self-assemble into micellesMicelles could bemultifunctional:tumor celltargeting andtherapeuticCourtesy ofAmanda Trent

Surfactant Number TheoryTheoretical approximation to predictmicro and nano structures‣ Our goal is to conjugatepeptides to tails in a way thatallows the resulting moleculesto self-assemble into sphericalmicelles.Cancer-targetingpeptides(Hydrophilic head)HydrophobictailR.S. Tu, M. Tirrell / Advanced Drug Delivery Reviews 56(2004) 1537–1563

1. Conjugation of a Peptide to a Hydrophobic TailC H 3TailONHCH 2Thiol-enereactionPeptideCys Ala Arg Glu Lys AlaDMPA(2,2-dimethoxy-2-phenylacetophenone)UV lightTail-head groupOC H 3NHCys Ala Arg Glu Lys Ala

Relative intensitymAu40003500300025002000150010005002. High Performance Liquid Chromatography(HPLC)0Increasing concentrationof acetonitrile40003500300025002000150010005000mAuSpargedReactionPeaks correspondto the tail-head group-500-5000.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 37.5 40.0 42.5 45.0 47.5 50.0 52.5 55.0 57.5 60.0MinutesTime40004000SealedReaction35003000350030002500250020002000Tail-head group :Tail-Cys (Gly) 7Ala Arg Glu Lys AlamAu1500100015001000mAu50050000-500-5000.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 37.5 40.0 42.5 45.0 47.5 50.0 52.5 55.0 57.5 60.0Minutes

3. Mass Spectrometry‣ After separating the different molecules in our solution,through the HPLC, we collect the ones we are interested in toanalyze their molecular weight.‣ In order to do so, we use a mass spectrometer.

Tail-Cys Gly 7Ala Arg Glu Lys AlaMolecular Weight: 1367.78 g/mol

Our Next Step:Conjugate Two Peptides to One TailC H 3TailONCH 2PeptideCys Ala Arg Glu Lys AlaCH 2DMPA(2,2-dimethoxy-2-phenylacetophenone)UV lightTail-head groupOC H 3NCys Ala Arg Glu Lys AlaCys Ala Arg Glu Lys Ala

Acknowledgements‣ Brian Lin, from Matt Tirrell’s Research Group‣ Dr. Nick Arnold and Dr. Jens Kuhn, from the INSETProgram.‣ Evelyn Hu and Liu-Yen Kramer, from CNSI‣ Dr. Michael Young and Dr. Alexander Horwitz, fromSanta Barbara City College

Thank you!Any questions?

DMPA (2,2-dimethoxy-2-phenyl acetophenone) is used as an initiator:OOO CH 3CH 3Under presence of UV light, cysteine will reactwith the tail (thiol-ene reaction):Cysteine (Cys)Glycine (Gly)Arginine (Arg)HSNH 2OOHN H 2NHNHNH 2OOHONH 2OHAlanine (Ala)C H 3ONH 2OHLysine (Lys)N H 2OOHNH 2Glutamic acid (Glu)HOONH 2OOH

Surfactant Number TheoryTheoretical approximationto predict micro and nanostructures:N v s =al ov: volume of the tail groupa: head group areal: fully extendedhydrocarbon tailR.S. Tu, M. Tirrell / Advanced Drug Delivery Reviews56 (2004) 1537–1563

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