Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability into the tumor microenvironment.
The capillary wall is the chief barrier to tissue entry of therapeutic nanoparticles, thereby dictating their efficacy. Collagen fibers are an important component of capillary walls, affecting leakiness in healthy or tumor vasculature. Using a computational model along with in vivo systems, we compared how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome (DOX-PLD) in tumor vasculature. We found a direct correlation between the collagen content around a tumor vessel to the permeability of that vessel permeability to DOX-PLD, indicating that collagen content may offer a biophysical marker of extravasation potential of liposomal drug formulations. Our results also suggested that while pharmacokinetics determined the delivery of DOX and DOX-PLD to the same tumor phenotype, collagen content determined the extravasation of DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper view into how nanotherapeutics cross biological barriers, possibly helping explain the balance between biological and physical aspects of drug delivery.
The Houston Methodist Research Institute; The University of Texas MD Anderson Cancer Center, Houston Texas; and.
Kenji
K
Yokoi
The Houston Methodist Research Institute; Belgrade Metropolitan University, Research and Development Center for Bioengineering, Kragujevac, Serbia.
Milos
M
Kojic
Belgrade Metropolitan University, Research and Development Center for Bioengineering, Kragujevac, Serbia.
Miljan
M
Milosevic
The Houston Methodist Research Institute;
Tomonori
T
Tanei
The Houston Methodist Research Institute;
Mauro
M
Ferrari
The Houston Methodist Research Institute; arturas.ziemys@gmail.com.
Arturas
A
Ziemys
D000818:Animals; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology*; D024141:Collagen Type IV / Q000032:analysis / Q000378:metabolism*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D059016:Tumor Microenvironment / Q000502:physiology
D024141:Collagen Type IV; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin