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Review
. 2011 Jul;102(7):1247-52.
doi: 10.1111/j.1349-7006.2011.01941.x. Epub 2011 May 3.

Nanomedicine in cancer therapy: innovative trends and prospects

Elvin Blanco  1 , Angela Hsiao, Aman P Mann, Matthew G Landry, Funda Meric-Bernstam, Mauro Ferrari
Affiliations
Review

Nanomedicine in cancer therapy: innovative trends and prospects

Elvin Blanco et al. Cancer Sci. 2011 Jul.

Abstract

Cancer is a leading cause of morbidity and mortality worldwide, with recent advancements resulting in modest impacts on patient survival. Nanomedicine represents an innovative field with immense potential for improving cancer treatment, having ushered in several established drug delivery platforms. Nanoconstructs such as liposomes are widely used in clinics, while polymer micelles are in advanced phases of clinical trials in several countries. Currently, the field of nanomedicine is generating a new wave of nanoscale drug delivery strategies, embracing trends that involve the functionalization of these constructs with moieties that enhance site-specific delivery and tailored release. Herein, we discuss several advancements in established nanoparticle technologies such as liposomes, polymer micelles, and dendrimers regarding tumor targeting and controlled release strategies, which are being incorporated into their design with the hope of generating a more robust and efficacious nanotherapeutic modality. We also highlight a novel strategy known as multistage drug delivery; a rationally designed nanocarrier aimed at overcoming numerous biological barriers involved in drug delivery through the decoupling of various tasks that comprise the journey from the moment of systemic administration to arrival at the tumor site.

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Figures

Figure 1
Figure 1
Established nanoparticle platforms for anticancer drug delivery. (A) Liposomes consisting of a hydrophobic membrane and an aqueous core accommodating hydrophilic drugs. (B) Polymer micelles consisting of a hydrophilic corona and a hydrophobic core encapsulating lipophilic drugs. (C) Dendrimers composed of multiple branches radiating from a central core.
Figure 2
Figure 2
Nanoparticle functionalization for active targeting and controlled release through external stimuli. Through active targeting, nanoparticles favor binding to receptors and integrins overexpressed on tumor endothelia or tumors, enhancing their site‐specific accumulation. Following localization at the tumor site, external stimuli such as ultrasound and temperature increases can be used to promote drug release.
Figure 3
Figure 3
Multistage drug delivery strategy for tumor treatment. The proposed mechanism of action of the multistage drug delivery strategy involves successful margination and attachment to tumor endothelia, accumulation at the tumor site, and release of drug‐containing second‐stage nanoparticles.
Figure 4
Figure 4
Properties and applications of multistage delivery particles for chemotherapy. (A) Bright‐field confocal microscopy, and overlay images of PEG‐FITC‐single‐walled carbon nanotubes (SWNT) (green) and quantum dots (red) loaded within a single mesoporous silicon particles (MSP). Bar, 3 μm. (B) Biodistribution of a variety of geometries of MSP and nanoparticles in different organs and tissues following intravenous injection, displayed as an in vivo percentage of silicon. Asterisks represent statistical significance (P < 0.001) between discoidal MSP. (C) Scanning Electron Microscopy image demonstrating internalization of MSP by endothelial cells (HUVEC) following incubation for 60 min at 37°C in serum‐free media. Bar, 5 μm. (D) Therapeutic efficacy of intravenously administered EphA2‐siRNA‐liposomes (DOPC) delivery by MSP (S1MP) in KOV3ip1 cells. SiRNA‐liposomes were injected biweekly at a dose of 5 μg siRNA for 3 weeks. A one‐time injection of S1MP‐EphA2‐siRNA‐DOPC was administered to mice at a dose of 15 μg siRNA. Asterisks represent statistical significance (P ≤ 0.05). (E) Longitudinal relaxivity measurements, r1, of hemispherical (H‐SiMP) and discoidal (D‐SiMP) MSP containing gadolinium contrast agents Magnevist (MAG), gadofullerenes (GF) and gadonanotubes (GNT) compared with corresponding gadolinium contrast agents. Reproduced with permission: A,E courtesy of Nature Publishing Group; B,C courtesy of Elsevier; and D courtesy of AACR Publications.
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