A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics

Abstract

The tumor microenvironment provides unique challenges for the delivery of chemotherapeutic agents in doses that are effective while ensuring minimal systemic toxicity. The primary limitation of current therapeutics is a lack of specificity in delivery, as they target healthy and cancerous cells alike. The development of nanoscale carriers capable of delivering cancer therapies has the potential to overcome both systemic and tumor barriers and provide specific, targeted delivery. This review seeks to provide an overview of available nanoscale drug carriers by exploring the wide variety of developed nanostructures and the most commonly used moieties for targeted delivery. Additionally, the use of nanoscale carriers will be motivated by examining tumor physiology and the specific barriers present within both the tumor microenvironment and systemic delivery.

Figure 1

Particle Schematics. (A) liposome, (B) micelle, (C) dendrimers functionalized with complexed (left) and encapsulated (right) drug molecules, (D) nanosphere, and (E) nanocapsule.

Figure 2

Targeted Particles: (A) Example of a folate receptor targeted particle. Liposome functionalized with PEG tethers to impart STEALTH characteristics and folate for tumor targeting (Hilgenbrink et al., 2005), (B) Folate-conjugated PLGA-PGA polymeric micelle loaded with encapsulated doxorubicin (Sudimak et al., 2000) and (C) cRGD-functionalized PCL-PEG polymeric micelle containing encapsulated doxorubicin (Nasongkla et al., 2004).

Figure 3

(a) Top. Antibody functionalization of the surface of nanoparticles composed of a 585nm silica core and a layer-by-layer deposition of alkyne-modified poly-(N-vinylpyrrolidone) and poly(methacrylic acid). Bottom. Antibody-functionalized particles added to a mixed population of cells that either expresses the complementary antigen (blue) or not (green). (b) Fluorescence microscopy images of huA33 mAb_Az-functionalized nanocapsules with (i) the antibody labeled with AF647 (red), or (ii) antibody labeled with AF488 (green), (iii) bright-field, and (iv) overlay images. (c) Deconvolution microscopy images of (left) antibody-functionalized or (right) IgG-functionalized nanocapsules. The particles were incubated with L1M1899 CRC cells at 37C for 24 hours. Capsules are labeled with AF647 (red), cells are labeled with LavaCell (green), and the nucleus is labeled with Hoechst 33342 (blue) (Johnston et al., 2012).

Figure 4

In vivo fluorescence imaging of nude mice bearing intracranial U87 MG glioma tumors after an intravenous injection of nanoparticles either (a) conjugated with Angiopep or (b) left bare. (c) Images of dissected organs from U87 MG glioma tumor-bearing mice, removed 24 hours after an injection of nanoparticles. We observe a collection of nanoparticles both at the tumor site in the brain (indicated by the arrows) and in the MPS/RES organs such as the liver and spleen. (d) TEM image of the PEG-PCL nanoparticles. (e) TEM image of the PEG-PCL nanoparticles after modification with Angiopep (Xin et al., 2011).