Utilization of monoclonal antibody-targeted nanomaterials in the treatment of cancer

Figures & data

Figure 1 Cellular uptake of mAb conjugated nanoparticle. mAb conjugated nanoparticles can be recognized by receptors on the cell membrane. Thus the nanoconjugates are internalized and trafficked along intracellular retrograde transport pathways.

Figure 2 Possible mechanisms of nanostructure extravasation. In the case of a continuous vascular endothelial barrier, nanostructures may be internalized by endothelial cells, e.g., via caveolae, transported via trans-cellular transport mechanisms and escape into the extracellular space via exocytosis. It is generally accepted that extravasation through tight gap junctions is limited to molecules or particles smaller than 10 nm.33,112 In the case of tumor vasculature, nanostructures may also escape the vasculature via transendothelial channels (TEC) and fenestrae. Molecules or particles up to 100 nm diameter may escape the vasculature via this route.1 Where the vasculature is sinusoidal/discontinuous (e.g., liver, spleen), nanostructures and large molecules may readily escape the vasculature.

Table 1 Monoclonal antibodies approved by the US food and drug administration for the treatment of cancer

Year	International non-proprietary name/Trade name	Target	Indication
1997	Rituximab/Rituxan	CD20	B-cell lymphoma
1998	Trastuzumab/Herceptin	HER2	Breast cancer
2001	Alemtuzumab/Campath	CD52	Chronic lymphocytic leukemia
2002	Ibritumomab tiuxetan/Zevalin	CD20	B-cell lymphoma
2003	Tositumomab/Bexxar	CD20	B-cell lymphoma
2004	Bevacizumab/Avastin	VEGF	Colon, lung, breast and renal cancer
2004	Cetuximab/Erbitux	EGFR	Colon; lung cancer
2006	Panitumumab/Vectibix	EGFR	Colon cancer
2009	Ofatumumab/Arzerra	CD20	Chronic lymphocytic leukemia
2011	Ipilimumab/Yervoy	CTLA-4	Melanoma

Note: The immunoconjugate gemtuzumab ozogamicin (Mylotarg^®) was approved by the US Food and Drug Administration in 2000 and withdrawn from marketing in 2010. Catumaxomab (Removab^®) was approved in the European Union in 2009.

Table 2 Types of nanomaterials utilized in the treatment of cancer, their advantages and limitations

Class of nanomaterial	Advantages	Limitations	Materials often utilized to construct nanomaterial
Liposomes	Amphiphilic, generally biocompatible, protect drugs from degradation	Large size, limited stability	Phosphatidylethanolamine, phosphatidylcholine, dioleoylphosphatidylethanolamine
Polymeric	Easily modified, some are biodegradable	Large scale uniform production is difficult, some exhibit cytotoxicity	PEG, PMLA, PGA, PLGA, block copolymers
Micelles	Easily modified, generally small size, biocompatible	Limited stability	Polyoxyethylene, polyoxypropylene, phosphatidylethanolamine
Metals	Unique optical properties, easily functionalized	Not biodegradable, tend to agglomerate when exposed to physiological environment	Gold, silver, platinum, copper
Non-metals	Stable and resistant to environmental changes, some possess unique physical properties	Generally not biodegradable, some have exhibited cytotoxic effects	Silica, carbon

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