Organic Nanoparticles as Anticancer and Theranostic Devices

HAL Id: hal-02913344

https://hal.archives-ouvertes.fr/hal-02913344

Submitted on 8 Aug 2020

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Organic Nanoparticles as Anticancer and Theranostic

Devices

V. Terrasson, M. Roy, F. Correard, M Esteve, D. Braguer, M. Gingras

To cite this version:

V. Terrasson, M. Roy, F. Correard, M Esteve, D. Braguer, et al.. Organic Nanoparticles as Anticancer and Theranostic Devices. RCOM8, 2014, Marseille, France. �hal-02913344�

Objectives :

• Application of dendrimers1,2_{in drug delivery and nanomedicine}

• Development of dendritic nanocarriers to overcome the drugs’ drawbacks

(low solubility in water of paclitaxel)

• Dendrimers engineered to disassemble into non toxic small molecules

easily eliminated from the body

V. Terrasson,a_{M. Roy,}a_{F. Correard,}b,c_{M.A. Esteve,}b,c_{D. Braguer}b,c_{and M. Gingras}a*

a_{Aix-Marseille Université, CNRS, CINaM UMR 7325, 163 avenue de Luminy, 13288 Marseille cedex 9, France} b_{Aix-Marseille Université, INSERM, CRO2 UMR 911, 13385 Marseille cedex 5, France}

c_{APHM, Hôpital Timone, 13385 Marseille, France}

Synthesis of Dendrimers

Ester linkage:

ACKNOWLEDGMENTS: ANR LaserNanoBio, CNRS, Aix-Marseille Université

Degradable anticancer device

Carbonate linkage:

Biological Evaluation

3-branched dendron PEG-ester-PTX paclitaxel

Branches of dendrimers are composed of:

- PEG chain (to increase hydrosolubility),

- linker biologically cleavable (ester, carbonate…), - paclitaxel (one of the most efficient anticancer drug).

A three-branched dendron with a gallic acid core (non toxic)

was synthesized

A carbonate linker can be used: comparison of the kinetics for the drug

release in the biological medium

Without treatment: cells display induvidual microtubules (green). With PTX or dendrimer-PTX: unattached and round cell phenotype.

Dendrimer-PTX complexes are cytotoxic on several cancer cell lines and display paclitaxel effect with prolonged drug

delivery (slow drug release by ester cleavage).

Ongoing syntheses of dendron linked to a fluorophor (for in

cellulo imaging) or bearing a

radioactive iodine (for in vivo imaging)

1_{M. Gingras, Designing Dendrimers (P. Ceroni, S. Campagna, F. Puntoriero; Eds), John Wiley & Sons, chapter 13 Degradable dendrimers, 403-463 (2012)}

2_{M. Gingras and M. Roy, Dendrimer-based Drug Delivery Systems: from Theory to Practice (Y. Cheng; Edr), John Wiley & Sons, chapter 7 Degradable dendrimers for Drug Delivery,}

239-303 (2012) O O O O MeO O O O O O O O O O OH O O OAc H O AcO OH O O O O NH O HO O O AcOH O AcO OH O O O O NH O HO O O AcOH O OAc OH O O O O NH O O O O O O O O O O O O O MeO O O O O O O O O O HO OH OH O O O O O O O O O OH O O O OH CH2Cl2, rt, 24h (5 eq) TsCl (1 eq) pyridine (5 eq) CH2Cl2, reflux, 4h O (1.5 eq) OTs O O O O O PPTS (1 %) DMF, 90°C, 18h (0.3 eq) MeO2C OH OH OH K2CO3(10 eq) O O O O MeO O O O O O O O O O OH OH OH MeOH, reflux, 3h PPTS (30 %) O O O N (15 eq) rt, 48h O PTX (3.3 eq) DCC (3.4 eq) CH2Cl2,0°C, 24 h 86 % 75 % 81 % 77 % 2/ 1/ 1/ 2/ DMAP (40 %)

Desymmetrization of PEG chain

Monofunctionalization

Multiple functionalization

Organic Nanoparticles as Anticancer and

Theranostic Devices