National Center for Design of
Biomimetic Nanoconductors
Image Index
A relatively large surface area allows the protocell to carry 1,000 times more cancer-killing cargo than a liposome. 
The liposomes used in cancer therapy are empty bilayer membranes, so their carrying capacity is limited by their interior volume. In contrast, the protocell's bilayer membrane is supported by a porous silica a comparative large surface area ( 1,200 cubic meters per gram). This gives the protocell a drug carrying capacity that is about 1,000 times that of an unsupported membrane.
The protocell accommodates a wide variety of cargo.
By altering the size and/or shape of the pores in the silica core, scientists can custom design the protocell to carry a wide array of molecules and concentrations.Small pores of about 2 nm can be designed to store high concentrations of low molecular weight molecules, such as those used in chemotherapy, while pores 10 nm to 30 nm in size can be loaded with smaller concentrations of large molecules, such as protein toxins and therapeutic RNAs.
Protocells bind more specifically to and kill human cancer liver cells more efficiently than free or liposomal encapsulated drug.
Confocal fluorescence microscopy reveals how rapidly the protocell and its contents are internalized by liver cancer cells but not by normal liver cells. In both the cancer cell (left) and the normal cell (right) the nucleus appears as a blue sphere within the main body of the cell (green). Visible within the cancer cell are small red dots located near the nucleus; those are protocell membranes. The numerous tiny white dots scattered throughout the interior of the cancer cell are the silica cores. Note that no red or white dots appear in the normal cell. Observing such images over time has revealed that in just 24 hours, each cancer cell internalizes approximately 1,000 protocells, while normal cells do not endocytose them at all.
After only four hours, the protocell and its contents can be seen inside the endosomes.
These fluorescent images show the wide variety of cargo that the protocell delivers to cancer cells. Endosomal delivery of the protocell and its contents occurs within four hours as revealed by the speckled pattern of the protocell's lipid membrane and silica core, as well as its four model cargos: calcein (similar to a low molecular weight chemotherapeutic drug); double-stranded DNA (mimics therapeutic RNA, which silences the expression of proteins involved in the proliferation of cancer); red fluorescent protein (mimics diptheria toxin, which kills cancer cells by inhibiting protein synthesis); and quantum dots (nanoparticles used in cancer imaging). In the second to last image on the lower right, the cell's cytosol appears purple, while the nucleus appears blue. The merged photo combines all of the images, revealing the cell-shaped distribution of the protocell's lipid membrane, silica core and cargo within the cancer cells.
Protocells can be tailored to deliver drugs and other molecules to specific areas of the cell.
Nuclear localization sequences direct the protocell and its contents to the nucleus, as seen in the images of NLS-linked calcein (top left) and double-stranded DNA (top row, second image from left). Note that the color in these two images is concentrated in the center of the cell, where the nucleus is located. In contrast, the color in the other images is doughnut-shaped around a dark center, indicating that the protocell contents remain located in the cytoplasm.
