Depending on the context, nanotechnologies developed as nanomedicines (nanosized therapeutics and imaging agents) are presented as either a remarkable technological revolution already capable of delivering new diagnostics, treatments for unmanageable diseases, and opportunities for tissue repair or highly dangerous nanoparticles, nanorobots, or nanoelectronic devices that will wreak havoc in the body. The truth lies firmly between these two extremes. Rational design of “nanomedicines” began almost half a century ago, and >40 products have completed the complex journey from lab to routine clinical use. Here we critically review both nanomedicines in clinical use and emerging nanosized drugs, drug delivery systems, imaging agents, and theranostics with unique properties that promise much for the future. Key factors relevant to the design of practical nanomedicines and the regulatory mechanisms designed to ensure safe and timely realization of healthcare benefits are discussed.

Nanomedicine(s) under the Microscope

Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines.

Development of HPMA copolymer–anticancer conjugates: Clinical experience and lessons learnt

Designer drug: A polymer therapeutic was designed for a combination therapy of breast cancer. N-(2-Hydroxypropyl)methacrylamide was used as the model polymer platform to prepare a unimolecular polymer conjugate (see picture, radius of gyration: 12.8 nm) that combines an endocrine (the aromatase inhibitor aminoglutethimide, blue) and a chemotherapeutic agent (the anthraxcycline antibiotic doxorubicin, red).

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200462960

Polymer therapeutics designed for a combination therapy of hormone-dependent cancer.

One-pot conversion of RAFT-generated multifunctional block copolymers of HPMA to doxorubicin conjugated acid- and reductant-sensitive crosslinked micelles.

Two poly-2-hydroxypropylmethacrylamide conjugates with the anti-cancer drug doxorubicin were investigated by1H NMR spectroscopy. In both polymers (FCE 28068 and FCE 28069) the drug is connected to a polymethacrylamide backbone via a tetrapeptidyl spacer (Gly-L,D-Phe–L-Leu–Gly) and, in addition, FCE 28069 contains similarly bound D-galactosamine molecules as liver-targeting moieties. Signals of the drug and galactosamine protons were fully assigned in the spectra of the polymers by means of NOESY and TOCSY experiments and by comparison with the spectra of reference compounds. The integrity of doxorubicin and the connectivity between the drug and peptidyl chain was successfully confirmed in spite of the comparatively low abundance (<5%) of the corresponding monomeric units and of signal spreading due to the diastereomeric mixture of peptidyl chains. Polymer-bound galactosamine molecules were found to be distributed among four isomeric forms (α- and β-anomers of pyranose and furanose forms, with predominance of the α-pyranose form). Diagnostic signals for possible alternative peptidyl chain endings (2-hydroxypropylamide or free carboxyl groups) were identified with the help of model polymers and the first, but not the second, were detected in the spectra of the two FCEs. In addition to the above results, high-field NMR is a rapid and sensitive method for the qualitative identification of low molecular weight contaminants in production batches of polymer–drug conjugates. © 1997 by John Wiley & Sons, Ltd.

F. Angelucci

Papers

1H NMR Characterization of Methacrylamide Polymer Conjugates with the Anti-Cancer Drug Doxorubicin