Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery Across Biological Barriers

Abstract

Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…33 It is reported that the NPs with 30−200 nm in hydrodynamic diameter accumulate with high efficiency in many solid tumors by EPR effect. 34 Distinguishingly, the fenestrations in the liver sinusoidal endothelium facilitate the substrate transfer into space of Disse between the liver sinusoid and hepatocytes in normal liver. The diameter of the fenestrations is ~78 ± 12 nm in wild-type mice.…”

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

“…These characters are known as the enhanced permeability and retention (EPR) effects that have been widely used to enhance the tumor selectivity of antitumor nanomedicines [6][7][8]. It was reported that with time the concentration of some intravenously (IV) administered nanosized anticancer drugs at the tumors could become several folds higher than that in normal tissues [9,10].…”

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

“…[8][9][10] Further, such nanocarriers can overcome chemoresistance by circumventing activation of extruding mechanisms and by protecting the drug from lysosomal degradation. 11,12 Nanoparticles can reach and accumulate within the tumor site passively, exploiting leaky and imperfect tumor neovascularization and defective lymphatic drainage, 13,14 or actively, by functionalizing the surface of the nanoparticles with ligands specifically directed to targets expressed on tumor cells. [15][16][17][18] Before a nanomaterial can be deemed a suitable theranostic tool, it is necessary to assess its ability to enter the cell, to reach the desired intracellular compartment (wherein the drug will be liberated), and to remain in the cell for a time period sufficient to allow adequate diagnostic and therapeutic functions.…”