Effects of Tumor Microenvironment on Hyperthermia, Photodynamic and Nanotherapy

  • Gianfranco Baronzio
  • Attilio Baronzio
  • Elisabetta Crespi
  • Isabel Freitas


A tumor mass is an association of normal cells and epigenetically modified cells in continuous evolution. Heterogeneous normal cell populations are forced to survive in a hostile environment in contact with cancer cells. Resident and recruited fibroblasts, and a complex infiltrate of neutrophils, macrophages, lymphocytes and mast cells work in concert with neoplastic cells to create a new, distinctive microenvironment that allows for the generation of a new interstitium and circulation (angioarchitecture). The tumor interstitium differs from normal interstitium in several ways (i.e., an elevated intracellular pH (pHi) and pressure (pi), a lowered extracellular pH (pHe), low oxygen concentrations and low glucose levels). These differences represent important characteristics that may be modulated positively or negatively by hyperthermia, photodynamic therapy and other treatment modalities. Furthermore, the tumor microcirculation creates barriers that hinder drug delivery to the tumor mass. Systemic chemotherapy often reduces tumor burden but rarely is effective in completely eliminating the tumor. This has created the need for the development of more effective cancer therapies. To this problem, a new class of drug delivery vehicles on the order of nanometer (nanocarriers, liposomes) has been developed to minimize side effects of chemotherapy and for directly targeting cancer cells. Notwithstanding their small dimensions, the distribution of these drugs is still influenced by tumor microenvironment. An overview of ways to overcome physiological barriers and exploit tumor pathogenesis for therapeutic gain is provided.


Drug delivery Barriers to drug delivery TIF EPR phenomenon Hyperthermia Photodynamic therapy Ultrasound drug delivery Magnetic hyperthermia Nanotherapy 


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© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Gianfranco Baronzio
    • 1
  • Attilio Baronzio
    • 2
  • Elisabetta Crespi
    • 3
  • Isabel Freitas
    • 4
  1. 1.Radiotherapy Hyperthermia DepartmentPoliclinico di Monza20052, MonzaItaly
  2. 2.Fellow Department of PharmacologyUniversity of Novara28100 NovaraItaly
  3. 3.Fellow Department of PharmacologyUniversity of Novara28100 NovaraItaly
  4. 4.Department of Animal Biology and IGM-CNR Center for Histochemistry & CytometryUniversity of PaviaPaviaItaly

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