Your friend has discovered a novel protein called Tumorbegone that enzymatically

Question

1. Your friend has discovered a novel protein called Tumorbegone that enzymatically destroys cancerous cells and tissues. She enlists you to adapt a nanocarrier to deliver this therapeutic protein systemically. The plan is that the nanocarrier will be taken up by the enhanced permeation and retention (EPR) effect
   1. Explain the physiological basis for the EPR effect.
   2. In your first attempt, you encapsulate the protein in a polycaprolactone (PCL) matrix. The particles are 110 nm in size when measured by DLS in phosphate buffered saline. However, when injected into mice, the particles are rapidly cleared. Explain the likely mechanism(s) for this.
   3. In your second attempt, you encapsulate the protein in a PCL-PEG matrix. The new particles are 120 nm in size when measured by DLS in phosphate buffered saline. When injected into mice, several percent of the injected dose distributes into the tumor within eight hours. Is the result consistent with the EPR effect, and what likely was different in the response of the mice to this new biomaterial?

1. Your friend has discovered a novel protein called Tumorbegone that enzymatically destroys cancerous cells and tissues. She enlists you to adapt a nanocarrier to deliver this therapeutic protein systemically. The plan is that the nanocarrier will be taken up by the enhanced permeation and retention (EPR) effect
   1. Explain the physiological basis for the EPR effect.
   2. In your first attempt, you encapsulate the protein in a polycaprolactone (PCL) matrix. The particles are 110 nm in size when measured by DLS in phosphate buffered saline. However, when injected into mice, the particles are rapidly cleared. Explain the likely mechanism(s) for this.
   3. In your second attempt, you encapsulate the protein in a PCL-PEG matrix. The new particles are 120 nm in size when measured by DLS in phosphate buffered saline. When injected into mice, several percent of the injected dose distributes into the tumor within eight hours. Is the result consistent with the EPR effect, and what likely was different in the response of the mice to this new biomaterial?

Explanation / Answer

a. The Enhanced permeability and retention effect calls for their extra accumulation in cancer cells in comparison to normal cells. This effect provides an efficient specific recognition for the sites of anticancer drug administration. This occurs due to the accumulation of nanoparticles into the tumor tissues and cells due to non-clearance in kidney.

b. If particles are cleared, it means their sizes are not so big that can evade the renal clearance.

c. The second attempt is adequate to identify the site of tumor.

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