HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations

Twan Lammers, Vladimir Subr, Karel Ulbrich, Peter Peschke, Peter Huber, Wim E. Hennink, Gert Storm, Fabian Kiessling

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

To assist intravenously administered anticancer agents in achieving proper circulation times and tumor concentrations, and to thereby improve the balance between their efficacy and their toxicity, a large number of drug delivery systems have been designed and evaluated over the years. Clinically relevant examples of such nanometer-sized carrier materials are liposomes, polymers, micelles and antibodies. In the vast majority of cases, however, and especially in patients, nanomedicine formulations are only able to attenuate the toxicity of the conjugated or entrapped chemotherapeutic drug, and they generally fail to improve the efficacy of the intervention. To overcome this shortcoming, and to broaden the clinical applicability of tumor-targeted nanomedicines, in the past 5 years we have developed several concepts for using N-(2-hydroxypropyl) methacrylamide (HPMA)-based polymer therapeutics to enhance the efficacy of combined modality anticancer therapy. Regarding surgery, HPMA copolymers were shown to be able to improve the retention of intratumorally administered chemotherapeutic agents at the pathological site, and to thereby increase their therapeutic index. Regarding radiotherapy, a synergistic interaction was observed, with radiotherapy improving the tumor accumulation of the copolymers, and with copolymers improving both the efficacy and the tolerability of radiochemotherapy. Futhermore, regarding chemotherapy combinations, we have for the first time provided in vivo evidence showing that passively tumor-targeted polymeric drug carriers can be used to deliver two different drugs to tumors simultaneously. Based on these findings, and on the fact that the concepts developed are considered to be broadly applicable, we conclude that nanomedicine formulations are highly suitable systems for improving the efficacy of combined modality anticancer therapy.

Original languageEnglish (US)
Pages (from-to)1501-1523
Number of pages23
JournalNanomedicine
Volume5
Issue number10
DOIs
StatePublished - Dec 2010

Fingerprint

chemotherapy
Chemotherapy
Radiotherapy
Combination Drug Therapy
tumor
Surgery
surgery
Tumors
Nanomedicine
Polymers
Medical nanotechnology
polymer
drug
Combined Modality Therapy
Copolymers
Neoplasms
Toxicity
toxicity
Therapeutics
Drug Carriers

Keywords

  • chemotherapy
  • combination therapy
  • drug targeting
  • hpma copolymers
  • image-guided drug delivery
  • nanomedicine
  • polymer therapeutics
  • radiotherapy
  • surgery
  • theranostics

ASJC Scopus subject areas

  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Development

Cite this

HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations. / Lammers, Twan; Subr, Vladimir; Ulbrich, Karel; Peschke, Peter; Huber, Peter; Hennink, Wim E.; Storm, Gert; Kiessling, Fabian.

In: Nanomedicine, Vol. 5, No. 10, 12.2010, p. 1501-1523.

Research output: Contribution to journalReview article

Lammers, T, Subr, V, Ulbrich, K, Peschke, P, Huber, P, Hennink, WE, Storm, G & Kiessling, F 2010, 'HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations', Nanomedicine, vol. 5, no. 10, pp. 1501-1523. https://doi.org/10.2217/nnm.10.130
Lammers, Twan ; Subr, Vladimir ; Ulbrich, Karel ; Peschke, Peter ; Huber, Peter ; Hennink, Wim E. ; Storm, Gert ; Kiessling, Fabian. / HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations. In: Nanomedicine. 2010 ; Vol. 5, No. 10. pp. 1501-1523.
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