Platinum theranostics – novel

anticancer drugs

By Gary Dowsett

What are theranostics?

MRI PET/SPECT Chemotherapy

Photodynamic

Gene Therapy

Radiation

Therapeutic

HyperthermiaNIR Fluorescence

Diagnostic + Theranostic =

Details published by Sneha S. Kelkar and Theresa M.Reineke1

Theranostics allows design of ‘compound drugs’ with multiple functionalities,

which may aid doctors to diagnose patients more effectively, rapidly and lead to

personalised medicine. Other advantages may include but are not limited to:

Overcoming drug resistance2

Improved relaxivity of imaging agents (hence improved imaging)

Specific targeting to target site (hence reduced toxicity)

Varying linker/spacer groups (unexpected activity? cost?)

Why theranostics?

Ultimate aim of projectSpacer – can use

various functionalities

to link molecules, e.g.

esters via. cyclic

anhydrides

MRI

contrasting

agent

derivative –

DOTA based

(DOTA-GA),

link via. cyclic

anhydride

spacer to

form ester

Therapeutic agent – cisplatin

derivative (oxoplatin). Pt(IV)

based

Targeting group -

RGD tripeptide

(L-Asp-Gly-L-Arg)3

Which molecules did this project aim to

make and why?

12

Retrosynthetic analysis – disconnection approach

What was achieved?

Before I started practical work:

Synthetic routes designed – Combination of research and retrosynthetic

analysis

Verification/changes

Project plan considering realistic time available

COSSH form assessments for all practical work

Ethical form assessments

Chemicals stock check and order forms completed

Background reading

Introduction to lab and cleaning

What was achieved?

After practical work had started:

Extensive review of literature covering state of the art MRI/cisplatin and

derivatives, previous theranostic research and synthetic methods

Continuous synthesis followed by characterisation at most stages – why was

this important? A) Expense B) Time C) Originality

Continuous write up Inc. electronic version and coded experiments

(each attempt)

Oral presentation Inc. Q&A with academics and peers and report

Project VIVA voce

What was achieved?

Some reactions carried out include:

What was achieved?

Linear RGD peptide

What was achieved?

Skills acquired/exercised:

Time management

Organisation

Independent laboratory skills/competency

Communication skills

Knowledge and experience developed in synthetic and analytical chemistry

A much deeper, education appreciation for scientific research

The End

References:

[1]- S. S. Kelkar and T. M. Reineke, Bioconjugate Chem, 2011, 22, 1879.

[2]- Alois Kozubík, Alena Vaculová, Karel Souček, Jan Vondráček, Jaroslav

Turánek, and Jiřina Hofmanová, Metal based drugs, 2008, 15, 2008.

[3]- J. A. Park, J. J. Lee, J. C. Jung, D. Y. Yu, C. Oh, S. Ha,T. J. Kim and Y. Chang,

ChemBioChem, 2008, 9, 2811.