Therapeutic Nanoparticles for Drug Delivery in Cancer

Abstract

Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve the biodistribution of cancer drugs, nanoparticles have been designed for optimal size and surface characteristics to increase their circulation time in the bloodstream. They are also able to carry their loaded active drugs to cancer cells by selectively using the unique pathophysiology of tumors, such as their enhanced permeability and retention effect and the tumor microenvironment. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumor targets amplify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle that impedes the efficacy of both molecularly targeted and conventional chemotherapeutic agents, might also be overcome, or at least reduced, using nanoparticles. Nanoparticles have the ability to accumulate in cells without being recognized by P-glycoprotein, one of the main mediators of multidrug resistance, resulting in the increased intracellular concentration of drugs. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.

PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…This is the foundation of the design of delivery systems targeted to endocytosis-prone surface receptors (Kirpotin et al, 2006;Danhier et al, 2010). The aptitude of the nanocarrier to be internalized after binding to target cell is so an significant criterion in the selection of proper targeting ligands (Cho et al, 2008;Danhier et al, 2010). In this strategy, ligand targeted nanocarriers will result in direct cell kill, including cytotoxicity against cells that are at the tumor periphery and are independent on the tumor vasculature (Pastorino et al, 2006;Danhier et al, 2010).…”

“…The transferrin receptor is a crucial protein involved in iron homeostasis and the regulation of cell growth. The high levels of expression of transferring receptor in cancer cells, which may be up to 100-fold higher than the regular expression of normal cells, its extracellular DOI:http://dx.doi.org/10.7314/APJCP.2014.15.2.517 PLGA-Based Nanoparticles as Cancer Drug Delivery Systems accessibility, its ability to internalize and its central role in the cellular pathology of human cancer, make this receptor an attractive target for cancer therapy (Cho et al, 2008;Danhier et al, 2010;Daniels et al, 2006). ii) The folate receptor is a famous tumor marker that binds to the vitamin folic acid and folate-drug conjugates or folate grafted nanocarriers with a high affinity and carries these bound molecules into the cells through receptormediated endocytosis.…”

Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

“…NPs have been associated with improvements in patient survival and quality of life by simultaneously increasing intracellular drug concentrations and reducing dose-limiting toxicity levels (Cho et al, 2008). Moreover, NPs could increase the solubility of a drug and enhance its safety and biocompatibility.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…[97] In this regard, nanotechnology has shown tremendous potential to develop and design various nanoparticles as a carrier for improved drug delivery, thereby reducing the undesired toxicity of the systemic delivery, increasing the drug dose at the tumor site and improve the overall efficacy of the drugs. [98][99][100] Loading of anticancer agents in nanoparticles have a number of advantages, including: (i) enhanced drug solubility and chemical stability; (ii) protection of the drug from degradation/metabolism and/or excretion; (iii) extended circulation half-life; (iv) improved tissue distribution; and (iv) controlled drug release properties. Furthermore, the nanoparticles can alter the pharmacokinetic (biodistribution) and pharmacodynamic (drug action) profiles of the anticancer drugs, resulting in enhanced therapeutic index.…”