Temperature-sensitive polymers to promote heat-triggered drug release from liposomes: Towards bypassing EPR

Mohamadreza Amin*, Twan Lammers, Timo L.M. ten Hagen

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

23 Citations (Scopus)
116 Downloads (Pure)


Heat-triggered drug release from temperature-sensitive nanocarriers upon the application of mild hyperthermia is a promising approach to achieve site-specific delivery of drugs. The combination of mild hyperthermia (41–42 °C) and temperature-sensitive liposomes (TSL) that undergo lipid phase-transition and drug release has been studied extensively and has shown promising therapeutic outcome in a variety of animal tumor models as well as initial indications of success in humans. Sensitization of liposomes to mild hyperthermia by means of exploiting the thermal behavior of temperature-sensitive polymers (TSP) provides novel opportunities. Recently, TSP-modified liposomes (TSPL) have shown potential for enhancing tumor-directed drug delivery, either by triggered drug release or by triggered cell interactions in response to heat. In this review, we describe different classes of TSPL, and analyze and discuss the mechanisms and kinetics of content release from TSPL in response to local heating. In addition, the impact of lipid composition, polymer and copolymer characteristics, serum components and PEGylation on the mechanism of content release and TSPL performance is addressed. This is done from the perspective of rationally designing TSPL, with the overall goal of conceiving efficient strategies to increase the efficacy of TSPL plus hyperthermia to improve the outcome of targeted anticancer therapy.

Original languageEnglish
Article number114503
JournalAdvanced Drug Delivery Reviews
Publication statusPublished - Oct 2022

Bibliographical note

The authors gratefully acknowledge support by the European Research Council (ERC Consolidator Grant 864121 : Meta-Targeting), and the German Research Foundation (DFG: GRK2375 (Project number: 331065168)).

Publisher Copyright:
© 2022 Elsevier B.V.


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