Nanotechnology in cancer therapy

Abstract

Cancer is one of the major causes of mortality worldwide and advanced techniques for therapy are urgently needed. The development of novel nanomaterials and nanocarriers has allowed a major drive to improve drug delivery in cancer. The major aim of most nanocarrier applications has been to protect the drug from rapid degradation after systemic delivery and allowing it to reach tumor site at therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as much as possible to reduce adverse effects. These nanocarriers are formulated to deliver drugs either by passive targeting, taking advantage of leaky tumor vasculature or by active targeting using ligands that increase tumoral uptake potentially resulting in enhanced antitumor efficacy, thus achieving a net improvement in therapeutic index. The rational design of nanoparticles plays a critical role since structural and physical characteristics, such as size, charge, shape, and surface characteristics determine the biodistribution, pharmacokinetics, internalization and safety of the drugs. In this review, we focus on several novel and improved strategies in nanocarrier design for cancer therapy.

FIGURE 1. Targeted therapy with RGD-Chitosan Nanoparticles

Binding efficiency of Alexa555 siRNA (red fluorescence) incorporated chitosan nanoparticles (CH-NP)- conjugated with RGD peptide (RGD-CH-NP) in SKOV3ip1 or A2780ip2 ovarian cancer cells (blue for nuclei) by fluorescence microscopy (Han et al., 2010). HAN, H. D., MANGALA, L. S., LEE, J. W., SHAHZAD, M. M., KIM, H. S., SHEN, D., NAM, E. J., MORA, E. M., STONE, R. L. & LU, C. 2010. Targeted gene silencing using RGD-labeled chitosan nanoparticles. Clinical Cancer Research, 16, 3910–3922.

FIGURE 2. Accumulation of siRNA with DOPC nanoliposomes in vivo

Fluorescent (A) and phase (B) view of liposomes after siRNA incorporation. C. Hematoxylin &Eosin stain of HeyA8 ovarian tumor. D. Autofluorescence in tumor 48 hours after intravenous administration of nonfluorescent control siRNA. E. Tumor accumulation of Alexa 555 siRNA (red fluoresce) incorporated in DOPC. F. Alexa 555 siRNA is seen in both tumor cells and surrounding macrophages (green) (Landen et al., 2005). LANDEN, C. N., CHAVEZ-REYES, A., BUCANA, C., SCHMANDT, R., DEAVERS, M. T., LOPEZ-BERESTEIN, G. & SOOD, A. K. 2005. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer research, 65, 6910–6918.

FIGURE 3. Sustained release of liposomal EphA2 siRNA in tumor cells

A. Alexa555-labeled siRNA oligos (red fluorescence) were packaged in DOPC nanoliposomes and loaded into Multistage Vector (MSV). Human ovarian tumor cells SKOV3ip2 and HeyA8 (nuclei in blue) were incubated with MSV/Alexa555 siRNA and release of Alexas555 siRNA from MSV was monitored by confocal microscopy over the next 7 days. B. Western blot analysis of EphA2 expression in SKOV3 cells incubated with MSV/EphA2 siRNA indicating inhibition in protein expression more than 7 days (Shen et al., 2013). SHEN, H., RODRIGUEZ-AGUAYO, C., XU, R., GONZALEZ-VILLASANA, V., MAI, J., HUANG, Y., ZHANG, G., GUO, X., BAI, L. & QIN, G. 2013. Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery. Clinical Cancer Research.