In vivo results in animal models:

• Brummelhuis ISG, Simons M, Lindner LH, Kort S, de Jong S, Hossann M, Witjes JA, Oosterwijk E. DPPG2-based thermosensitive liposomes as drug delivery system for effective muscle-invasive bladder cancer treatment in vivo. Int. J. Hyperthermia. 2021;38:1415–1424.
• Hossann M, Hirschberger J, Schmidt R, Baumgartner C, Zimmermann K, Baer S, Ratzlaff C, Peller M, Troedson K, Limmer S, Brühschwein A, Dörfelt R, Kreutzmann N, Wess G, Knösel T, Schagon O, Fischer J, Grüll H, Willerding L, Schmidt M, Meyer-Lindenberg A, Issels RD, Schwaiger M, Eggermont AM, Ten Hagen TL, Lindner LH. A heat-activated drug delivery platform based on phosphatidyl-(oligo)-glycerol nanocarrier for effective cancer treatment. Advanced NanoBiomed Research. 2021;1:2000089.
• Lokerse WJM, Lazarian A, Kleinhempel A, Petrini M, Schwarz P, Hossann M, Holdt LM, Mailänder V, Lindner LH. Mechanistic investigation of thermosensitive liposome immunogenicity and understanding the drivers for circulation half-life: A polyethylene glycol versus 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol study. J Control Release. 2021;333:1-15.
• van Valenberg FJP, Brummelhuis ISG, Lindner LH, Kuhnle F, Wedmann B, Schweizer P, Hossann M, Witjes JA, Oosterwijk E. DPPG2-based thermosensitive liposomes with encapsulated doxorubicin combined with hyperthermia lead to higher doxorubicin concentrations in the bladder compared to conventional application in pigs: a rationale for the treatment of muscle-invasive bladder cancer. Int J Nanomedicine. 2021:16:75-88.
• Zimmermann K. Hossann M. Hirschberger J. Troedson K. Peller M. Schneider M. Bruehschwein A. Meyer-Lindenberg A. Wess G. Wergin M. Doerfelt R. Knoesel T. Schwaiger M. Baumgartner C. Brandl J. Schwamberger S. Lindner LH A pilot trial of doxorubicin containing phosphatidyldiglycerol based thermosensitive liposomes in spontaneous feline soft tissue sarcoma. Int. J. Hyperthermia. 2017;33:178-190.
• Peller M, Willerding L, Limmer S, Hossann M, Dietrich O, Ingrisch M, Sroka R, Lindner LH. Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors. J Control Release. 2016 Sep 28;237:138-146.
• Willerding L, Limmer S, Hossann M, Zengerle A, Wachholz K, ten Hagen TLM, Koning GA, Sroka R, Lindner LH, Peller M. Method of hyperthermia and tumor size influences effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors. J Control Release. 2016 Jan 28;222:47-55.
• Limmer S, Hahn J, Schmidt R, Wachholz K, Zengerle A, Lechner K, Eibl H, Issels RD, Hossann M, Lindner LH. Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes. Pharm Res. 2014 Sep;31(9):2276-86.
• Peller M, Schwerdt A, Hossann M, Reinl HM, Wang T, Sourbron S, Ogris M, Lindner LH. MR characterization of mild hyperthermia-induced gadodiamide release from thermosensitive liposomes in solid tumors. Invest Radiol. 2008 Dec;43(12):877-92.
• Lindner LH, Eichhorn ME, Eibl H, Teichert N, Schmitt-Sody M, Issels RD, Dellian M. Novel temperature-sensitive liposomes with prolonged circulation time. Clin Cancer Res. 2004 Mar 15;10(6):2168-78.

Formulation development and in vitro results:

• Rysin A, Paal M, Lokerse WJM, Wedmann B, Hossann M, Vogeser M, Winter G, Lindner LH. Evaluation of release and pharmacokinetics of hexadecylphosphocholine (miltefosine) in phosphatidyldiglycerol-based thermosensitive liposomes. Biochim Biophys Acta. 2021;1863:183698.
• Petrini M, Lokerse WJM, Mach A, Hossann M, Merkel OM, Lindner LH. Effects of surface charge, PEGylation and functionalization with dipalmitoylphosphatidyldiglycerol on liposome–cell interactions and local drug delivery to solid tumors via thermosensitive liposomes. Int J
  Nanomedicine. 2021;16:4045-4061.
• Mittag JJ, Kneidl B, Preiß T, Hossann M, Winter G, Wuttke S, Engelke H, Rädler Impact of plasma protein binding on cargo release by thermosensitive liposomes probed by fluorescence correlation spectroscopy. Eur J Pharm Biopharm. 2017 Oct;119:215-223.
• Hossann M, Wang T, Syunyaeva Z, Wiggenhorn M, Zengerle A, Issels RD, Reiser M, Lindner LH, Peller M. Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes. J Control Release. 2013 Feb 28;166(1):22-9.
• Hossann M, Syunyaeva Z, Schmidt R, Zengerle A, Eibl H, Issels RD, Lindner LH. Proteins and cholesterol lipid vesicles are mediators of drug release from thermosensitive liposomes. J Control Release. 2012 Sep 10;162(2):400-6.
• Hossann M, Wang T, Wiggenhorn M, Schmidt R, Zengerle A, Winter G, Eibl H, Peller M, Reiser M, Issels RD, Lindner LH. Size of thermosensitive liposomes influences content release. J Control Release. 2010 Nov 1;147(3):436-43.
• Wang T, Hossann M, Reinl HM, Peller M, Eibl H, Reiser M, Issels RD, Lindner LH. In vitro characterization of phosphatidylglyceroglycerol-based thermosensitive liposomes with encapsulated 1H MR T1-shortening gadodiamide. Contrast Media Mol Imaging. 2008 Jan-Feb;3(1):19-26.
• Lindner LH, Hossann M, Vogeser M, Teichert N, Wachholz K, Eibl H, Hiddemann W, Issels RD. Dual role of hexadecylphosphocholine (miltefosine) in thermosensitive liposomes: active ingredient and mediator of drug release. J Control Release. 2008 Jan 22;125(2):112-20.
• Hossann M, Wiggenhorn M, Schwerdt A, Wachholz K, Teichert N, Eibl H, Issels RD, Lindner LH. In vitro stability and content release properties of phosphatidylglyceroglycerol containing thermosensitive liposomes. Biochim Biophys Acta. 2007 Oct;1768(10):2491-9.

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• Dewhirst MW, Secomb TW. Transport of drugs from blood vessels to tumour tissue. Nat Rev Cancer. 2017 Dec;17(12):738-50.

• Manzoor AA, Lindner LH, Landon CD, Park JY, Simnick AJ, Dreher MR, Das S, Hanna G, Park W, Chilkoti A, Koning GA, ten Hagen TL, Needham D, Dewhirst MW. Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 2012 Nov 1;72(21):5566-75.
• Gasselhuber A, Dreher MR, Rattay F, Wood BJ, Haemmerich D. Comparison of conventional chemotherapy, stealth liposomes and temperature-sensitive liposomes in a mathematical model. PLoS One. 2012;7(10):e47453.

Thermosensitive liposomes:

• Dou Y. Hynynen K. Allen C. To heat or not to heat: Challenges with clinical translation of thermosensitive liposomes. J Control Release. 2017 Mar 10:249:63-73
• Kneidl B, Peller M, Winter G, Lindner LH, Hossann M. Thermosensitive liposomal drug delivery systems: state of the art review. Int J Nanomedicine. 2014 Sep 16;9:4387-98.
• Hijnen N, Langereis S, Gruell H. Magnetic resonance guided high-intensity focused ultrasound for image-guided temperature-induced drug delivery. Adv Drug Deliv Rev. 2014 Jun;72:65-81.
• May JP, Li SD. Hyperthermia-induced drug targeting. Expert Opin Drug Deliv. 2013 Apr;10(4):511-27.
• Grüll H, Langereis S. Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound. J Control Release. 2012 Jul 20;161(2):317-27.
• Koning GA, Eggermont AM, Lindner LH, ten Hagen TL. Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharm Res. 2010 Aug;27(8):1750-4.

Stimuli-responsive drug delivery (in general):

• Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013 Nov;12(11):991-1003.

Deep regional hyperthermia for locally advanced high-risk soft tissue sarcoma:

• Issels RD, Noessner E, Lindner LH, Schmidt M, Albertsmeier M, Blay JY, Stutz E, Xu Y, Buecklein V, Altendorf-Hofmann A, Abdel-Rahman S, Mansmann U, von Bergwelt-Baildon M, Knoesel T. Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial. Eur J Cancer. 2021; 158:123-132
• Lindner LH, Blay J, Eggermont AMM, Issels RD. Perioperative chemotherapy and regional hyperthermia for high-risk adult-type soft tissue sarcomas. Eur J Cancer. 2021:147:164e169
• Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Duerr HR, Knoesel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A. Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial. JAMA Oncol. 2018 Feb 15.
• Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822.
• Reichardt P and Lindner LH. Chemotherapy in advanced soft tissue sarcomas. In Blay JY (Eds.), 100 Key Questions on Soft Tissue Sarcoma, 2nd edition. Permanyer 2016.
• Issels RD, Lindner LH. Regional hyperthermia for high-risk soft tissue sarcoma treatment: present status and next questions. Curr Opin Oncol, 2016 Sep;28(5):447-52.
• Issels RD, Lindner LH, Ghadjar P, Reichardt P, Hohenberger P, Verweij J, Abdel-Rahman S, Daugaard S, Salat C, Vujaskovic Z, Wessalowski R, Duerr HR, Ploner F, Mella O, Schmidt M, Mansmann U, Jauch KW, Belka C, Hiddemann W, Gronchi A. Improved overall survival by adding regional hyperthermia to neoadjuvant chemotherapy in patients with localized high-risk soft tissue sarcoma (HR-STS): Long-term outcomes of the EORTC 62961/ESHO randomized phase III study, European Cancer Congress (ECC 2015), Late braking abstract, Vienna, Austria – 25 Sep – 29 Sep 2015.
• Fendler WP, Chalkidis RP, Ilhan H, Knoesel T, Herrmann K, Issels RD, Bartenstein P, Cyran CC, Lindner LH, Hacker M. Evaluation of several FDG PET parameters for prediction of soft tissue tumour grade at primary diagnosis and recurrence. Eur Radiol. 2015 Aug;25(8):2214-21.
• Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG); European Society for Hyperthermic Oncology (ESHO). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localized high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70.
• Wendtner CM, Abdel-Rahman S, Krych M, Baumert J, Lindner LH, Baur A, Hiddemann W, Issels RD. Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas. J Clin Oncol. 2002 Jul 15;20(14):3156-64.

Deep regional hyperthermia for refractory non-testicular germ cell tumors:

• Wessalowski R, Schneider DT, Mils O, Friemann V, Kyrillopoulou O, Schaper J, Matuschek C, Rothe K, Leuschner I, Willers R, Schönberger S, Göbel U, Calaminus G; MAKEI study group. Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study. Lancet Oncol. 2013 Aug;14(9):843-52.

Deep regional hyperthermia for cervical cancer:

• Franckena M, Stalpers LJ, Koper PC, Wiggenraad RG, Hoogenraad WJ, van Dijk JD, Wárlám-Rodenhuis CC, Jobsen JJ, van Rhoon GC, van der Zee J. Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial. Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1176-82.
• van der Zee J, González González D, van Rhoon GC, van Dijk JD, van Putten WL, Hart AA. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet. 2000 Apr 1;355(9210):1119-25.

Hyperthermia for superficial bladder cancer:

• Arends TJ, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F, Moskovitz B, van der Heijden AG, Witjes JA. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol. 2016 Jan 20. pii: S0302-2838(16)00057-9.
• Colombo R, Da Pozzo LF, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. J Clin Oncol. 2003 Dec 1;21(23):4270-6.

Additional scientific papers about clinical application of local/regional hyperthermia:

• Issels R, Kampmann E, Kanaar R, Lindner LH. Hallmarks of hyperthermia in driving the future of clinical hyperthermia as targeted therapy: translation into clinical application. Int J Hyperthermia. 2016 Jan 24:1-7.
• Januszewski A, Stebbing J. Hyperthermia in cancer: is it coming of age? Lancet Oncol. 2014 May;15(6):565-6.
• Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer. 2008 Nov;44(17):2546-54.
• Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag PM. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002 Aug;3(8):487-97.

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• Hijnen NM, Kneepkens ECM, de Smet M, Heijman E, Langereis S, Gruell H. Thermal Combination Therapies for Local Drug Delivery by Magnetic Resonance-guided High Intensity Focused Ultrasound. PNAS. 2017 May;114(24):E4802-E4811.
• Staruch RM, Hynynen K, Chopra R. Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: Therapeutic effect in rabbit Vx2 tumours. Int J Hyperthermia 2015 Mar;31(2):118-33.
• de Smet M, Hijnen NM, Langereis S, Elevelt A, Heijman E, Dubois L, Lambin P, Gruell H. Magnetic Resonance Guided High-Intensity Focused Ultrasound Mediated Hyperthermia Improves the Intratumoral Distribution of Temperature-Sensitive Liposomal Doxorubicin. Invest Radiol. 2013 Jun;48(6):395-405.
• Partanen A, Yarmolenko PS, Viitala A, Appanaboyina S, Haemmerich D, Ranjan A, Jacobs G, Woods D, Enholm J, Wood BJ, Dreher MR. Mild hyperthermia with magnetic resonance-guided high-intensity focused ultrasound for applications in drug delivery. Int J Hyperthermia. 2012;28(4):320-36.
• de Smet M, Heijman E, Langereis S, Hijnen NM, Gruell H. Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: an in vivo proof-of-concept study. J Control Release. 2011 Feb 28;150(1):102-10.