Nanoparticle Therapeutics: An Emerging Treatment Modality for Cancer
So far, large numbers of preclinical studies have been published on nanoparticle therapeutics, but still has remarkable potential therapeutic effects. Nanoparticle therapeutics are typically particles consisting of therapeutic entities, such as small-molecule drugs, peptides, proteins and nucleic acids, where components are assembled with therapeutic entities, such as lipids and polymers, to form nanoparticles. These nanoparticles have been found to enhance anticancer efficacy by improving pharmacokinetics and pharmacodynamics, as well as active intracellular delivery to target tumor tissues more specifically and reduce side effects.
The anticancer properties of nanoparticles depend on the size and surface properties of nanoparticles and the presence of targeted ligands. Generally speaking, nanoparticles used to treat cancer are currently thought to be in the 10-100 nm range in diameter. Within this range, the surface charge is either slightly positive or slightly negative and should have accessibility to and within disseminated tumors when the nanoparticles dosed into the circulatory system. Moreover, nanoparticles have high surface-to-volume ratios compared to larger particles, so controlling their surface properties, such as steric stabilization and surface charge control, to minimize nonspecific interactions helps prevent nanoparticles from being lost to undesired locations. Lastly, the addition of targeted ligands provides specific nanoparticle-cell surface interactions that can play an important role in the ultimate position of nanoparticles. Recent studies have compared non-targeting and targeted nanoparticles, the results show that the main role of targeted ligands is to enhance the cellular uptake of cancer cells, rather than tumor accumulation. By carefully controlling the size and surface properties of nanoparticles, they can be adjusted to provide long or short circulation times. Besides, they can be targeted to specific cell types in the target organ. At present, nanoparticles have been used as anticancer drugs and achieved good results.
The types of nanoparticles without targeting ligands include liposomes, polymer micelles and polymer-based nanoparticles. Studies have shown that such nanoparticles alter the pharmacokinetic properties of drug molecules. Compared with the use of free drugs alone, nanoparticles have a longer cycle time and can improve tumor uptake. A typical drug of non-targeting nanoparticles, Doxil has been used in the clinic for over two decades and it has been discussed extensively elsewhere. Numerous other liposomes containing drugs such as irinotecan and SN-38 are currently in clinical troxil. Also, multifunctional non-targeting nanoparticles such as IT-101, reducing side effects without the generation of new toxicities compared with the drug that is contained within them. The particle will be tested in clinical trials as maintenance ovarian cancer therapy. if successful, this will open up a new paradigm for nanoparticle therapeutics based on their potential to provide low toxicity and high efficacy.
Similarly, nanoparticles with targeted ligands are also used as anticancer drugs in the clinic. The study suggests that the leaky vasculature of tumors allows nanoparticles to extravasate, whereas normal vascular systems do not (a property that involves changes in the biodistribution of nanoparticles, as opposed to drug molecules). Therefore, active targeting by adding targeting ligands to nanoparticles is envisioned to provide the most effective therapy.
In summary, recent comparisons of nontargeted and targeted nanoparticles have shown that the primary role of the targeting ligands is to enhance cellular uptake into cancer cells and to minimize the accumulation in normal tissue. This behavior suggests that the colloidal properties of nanoparticles will determine their biodistribution, whereas the targeting ligand serves to increase the intracellular uptake in the target tumor. And recently, Zhou et al. from Emory University proved that the affinity density relationships of nanoparticles can be determined. The result illustrates that the importance of the multivalency of targeted nanoparticles. These preclinical and clinical studies of nanoparticle therapeutics are likely to affect clinical investigations and their implications for advancing the treatment of patients with cancer.
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