Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors

Abstract

Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study.

Keywords: antineoplastic drugs; nanosystems; nanotheranostics; poor aqueous solubility; solid tumors; targeted drug delivery.

Figure 1

Estimated age-standardized incidence rate (worldwide) per 100,000 population. Note: *Region estimates do not sum to the worldwide estimate due to the calculation method.

Figure 2

Illustrative representation of the various types of interactions between bioreceptors and analytes, as well as the measurable signals that are produced.

Figure 3

Diagrammatic representation of the factors contributing to the enhanced permeability and retention phenomenon displayed by tumor tissue.

Figure 4

(A) Diagrammatic comparison of the internalization mechanisms of free drug and nanodrug delivery systems in normal tumor cells and multidrug-resistant tumor cells. (B) Confocal microscopic images of Caco-2 cells after 1 hour incubation at 37 °C with coumarin 6-loaded PLGA nanoparticles coated with (a) PVA or (b) vitamin E TPGS. The cells were stained by propidium iodide (red) and uptake of green fluorescent 6-coumarin-loaded nanoparticles in Caco-2 cells was visualized by overlaying images obtained by FITC filter and RITC filter. The two figures show a distinct extent in cellular uptake of the nanoparticles. Note: (A) Reprinted from Journal of Controlled Release, 162(1), Gao Z, Zhang L, Sun Y, Nanotechnology applied to overcome tumor drug resistance, 45–55, Copyright © 2012, with permission from Elsevier. (B) Reprinted from Biomaterials, 26(15), Win KY, Feng S-S, Effect of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs, 2713-2722, Copyright © 2005, with permission from Elsevier. Abbreviations: DDS, drug delivery system; MDR, multidrug resistance; RES, reticuloendothelial system; PLGA, poly(lactic-co-glycolic acid); PVA, polyvinyl alcohol; vitamin E TPGS, vitamin E succinated polyethylene glycol 1000; FITC, fluorescein isothiocyanate; RITC, rhodamine B isothiocyanate.

Figure 5

Illustration of the change in chemical structure from the highly active lactone form to the less active carboxylate form of camptothecin at physiological pH. Abbreviation: HSA, human serum albumin.

Figure 6

Illustration of the potential of nanotheranostic systems in personalizing treatment and improving therapeutic outcomes in cancer. Note: Reprinted from Advanced Drug Delivery Reviews, 64(13), Mura S, Couvreur P, Nanotheranostics for personalized medicine, 1394-1416, Copyright © 2012, with permission from Elsevier. Abbreviations: SPIO, superparamagnetic iron oxide; NPs, nanoparticles; NSs, nanospheres; QDs, quantum dots; PFOB, perfluorooctylbromide; ROS, reactive oxygen species; Au, Gold.

Figure 7

Innovative nanoconstructs with tumor theranostic application. (A) A self-assembling terpolymer nanoparticle containing doxorubicin. (B) A nanoshell theranostic system consisting of a dielectric silica core and a shell composed of an initial gold layer and a second layer of silica containing an imaging dye and iron oxide nanoparticles. (C) A self-assembling mesoporous nanoparticle encapsulating carbon, with silica nanocrystals embedded in the mesoporous nanoparticle wall. This nanosystem is further conjugated with phospholipids and polysaccharides. (D) A self-assembling lipid-micellar nanoparticle with a manganese core and either doxorubicin or DNA therapeutic agent. Notes: (A) Reprinted from Journal of Controlled Release, 167(1), Shalviri A, Foltz WD, Cai P, Rauth AM, Wu XY, Multifunctional terpolymeric MRI contrast agent with superior signal enhancement in blood and tumor, 11–20, Copyright © 2013, with permission from Elsevier. (B) Reprinted from Advanced Drug Delivery Reviews, 64(13), Mura S, Couvreur P, Nanotheranostics for personalized medicine, 1394-1416, Copyright © 2012, with permission from Elsevier. (C) Reprinted from Biomaterials, 33(17), He Q, Ma M, Wei C, Shi J, Mesoporous carbon@silicon-silica nanotheranostics for synchronous delivery of insoluble drugs and luminescence imaging, 4392–4402, Copyright © 2012, with permission from Elsevier. (D) Reprinted from Journal of Controlled Release, 167(2), Howell M, Mallela J, Wang C, et al, Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs, 210–218, Copyright © 2013, with permission from Elsevier. Abbreviations: PS 80, polysorbate 80; PMAA, poly(methacrylic acid); NIR, near infra red; Dope, dioleoylphosphatidyl-ethanolamine; DC, 3β-[N-(N′-dimethylaminoethane)-carbamoyl; PEG, polyethylene glycol; PE, phosphatidylethanolamine; PL-1, payload 1; PL-2, payload 2; DSPE, distearoylphosphatidylethanolamine; MSNs, mesoporous silca nanoparticles; CS, carbon and silica nanocrystals; CPT, camptothecin; DOX, doxorubicin; NPs, nanoparticles.

Figure 8

Illustrative representation of the mechanism of photosensitizers for photodynamic therapy. Note: Reprinted from Cancer Letters, 327(1–2), Spyratou E, Makropoulou M, Mourelatou EA, Demetzos C, Biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy, 111–122, Copyright © 2012, with permission from Elsevier. Abbreviation: ROS, reactive oxygen species.