Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates

Abstract

A new antibody-drug conjugate (ADC) chemical drug-linker platform based on polysarcosine enables increased drug-loading, improved pharmacokinetics and exquisite in vivo potency.

Thermoresponsive polysarcosine-based nanoparticles

“…18 Recent literature examples of PSar-based systems that have broad potential as drug delivery/controlled release vehicles include the creation of amphiphilic block copolymers composed of PSar and poly(εcaprolactone) that are capable of undergoing thermallymediated self-assembly to bear a range of (nano)carriers, 19 amphiphilic star-like copolymers consisting of PSar and Bocprotected polylysine, that undergo degradation in response to elevated glutathione concentration, 20 and very recently the creation of β-glucuronidase-responsive antibody drug conjugates (ADC) that feature PSar as a hydrophobicity masking entity within an ADC drug-linker platform. 21 Recent work within our laboratory includes the creation of PSar-containing block copolymers, polymerised from a therapeutic initiator, that form enzyme-responsive nanoparticles, 22 and the creation of poly(amino acid)-poly(ester) conjugates synthesised by glucosamine-initiated ring-opening polymerisation, that are susceptible to acid-mediated degradation. 23 Such promising results ensure that additional investigation into the use of PSar as a component within controlled release systems is of value.…”

Antibody Conjugates-Recent Advances and Future Innovations

“…The DAR number has a strong influence on the properties of ADCs. Currently, many of the ADCs in the clinic have DAR numbers in the range of 2-4, although ADCs with higher DAR numbers have also been reported [31,[155][156][157][158]. For stochastically conjugated ADCs, the small molecule drug is covalently linked to either the lysine or the interchain cysteine residues of the antibody, resulting in a heterogeneous mixture with various DAR species which are more difficult to characterize and control.…”

Monitoring glycosidase activity for clustered sugar substrates, a study on β-glucuronidase

“…2 has been selected due to its widespread use in the design of enzyme-responsive prodrugs. [29][30][31] Such aromatic linkers bearing a nitro group allow a fast liberation kinetics of the drugs. 32 Amino-coumarin functionalized by a propargyl-oxo-carbonyl group was previously shown to be virtually non-uorescent but was converted into a highly uorescent amino-coumarin aer palladium-triggered depropargylation.…”