Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance

Abstract

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics.

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

“…However, to date, only 2 nanoformulations for cancer treatment have been approved for clinical use (liposomal doxorubicin [Doxil] and protein-bound paclitaxel [Abraxane]) (1-3). One major obstacle for the use of nanoparticles in vivo is rapid clearance by the cells of the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS) (4)(5)(6)(7). In addition to rapid clearance, variable activity of the MPS among patients leads to widely variable pharmacokinetics of nanoformulations in the clinic, reducing the efficacy of both approved and future experimental nanoformulations (8).…”

“…PEGylation of particles clearly extends their circulation time in vivo (4,10); however, up to 25% of patients exhibit circulating anti-PEG antibodies prior to treatment or develop anti-PEG antibodies after the first administration of PEGylated particles (11,12). These factors limit the utility of PEGylation of nanoparticles in the clinic and suggest that a better understanding of the biomolecular interactions of nanoparticles and the MPS is critical for the development of alternative methods to PEGylation that will extend nanoparticle circulation times in vivo.…”

Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

“…Among these general approaches, the role of nanomedicines exploiting active targeting via specific ligands is increasing in prominence [8][9][10] . These efforts have met with varying success [5][6][7] , and it is not always possible to fully explain the different outcomes.…”

Emerging therapies for pancreatic ductal carcinoma

“…Potential nanotechnology platforms for drug delivery include liposomes, dendrimers, gold nanoshells, polymer-based nanoparticles and micelles, and metallic and magnetic nanoparticles. [36,37] Liposomes are lipid-based vesicles that can carry hydrophilic molecules in their aqueous compartment or they can carry hydrophobic molecules in their lipid bilayer. [38] Dendrimers have repeating branches stemming from a central core.…”