Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles.
Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided.
Drug Delivery and Formulation, Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada; Ryerson University, Faculty of Architectural Science and Engineering, Toronto, Ontario M5B 1Z2, Canada.
Mark J
MJ
Ernsting
Mami
M
Murakami
Aniruddha
A
Roy
Shyh-Dar
SD
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D014018:Tissue Distribution
D000970:Antineoplastic Agents
Biodistribution; Intratumoral penetration; Nanoparticle; Pharmacokinetics; Tumor microenvironment