Nanophotothermolysis: IPL Treatment with Targeted AuNP for Colorectal Cancer Therapy Modeled by Monte Carlo Simulations

Overview

Objectives/Goals Chemotherapy causes harmful side effects by destroying healthy cells in addition to cancerous ones. Attaching cancer seeking ligands to nanoparticles can direct drugs to cancer sites to boost drug efficacy and reduce toxicity. Since the folate receptor is upregulated in cancer with limited distribution in normal cells, folate conjugated gold nanoparticles (AuNP) can be synthesized for cancer targeting. AuNP also have a unique surface plasmon resonance property which converts light photons to heat for cancer cell destruction in a new process called nanophotothermolysis. I hypothesize that IPL treatment will be effective in destroying significantly more colon cancer cells than normal fibroblast cells when incubated with optimal sized folate conjugated AuNP. Methods/Materials I created a computer modeling algorithm with Monte Carlo Simulations to determine optimal AuNP kinetics for endocytosis by testing 9 parameters in 1000 simulation runs. I synthesized gold nanospheres with inversely proportional amounts of sodium citrate to HAuCl4 in 13nm, 26nm, 52nm and 104nm sizes. After characterizing uptake of nanospheres in Rat-2 fibroblast cells using UV-Vis spectra and TEM, I prepared samples for ICP-MS. I developed a method to create optimal sized folate-AuNP . I applied IPL treatment to GPC-16 cells and Rat-2 fibroblast cells with folate-AuNP using a filtered xenon flash lamp of wavelengths between 400 to 1100 nm and fluence of 6 joules/cm2. I prepared Trypan blue cell viability assays measuring cell counts with a hemocytometer and recorded the results. Results In silico molecular docking and bending energy modeling predicted AuNP size dependent endocytosis with optimal uptake of nanoparticles size in the 40-60nm range. In vitro analysis with UV-Vis spectra and ICP-MS measured greatest gold concentration uptake of gold AuNP with diameters of 52 nm. IPL treatment targeting cancers cells with overexpression of folate receptors destroyed 80% cancers cells with folate conjugated AuNp and only 20% of the normal fibroblast cells. Conclusions/Discussion A new energy transfer model simulating size dependent endocytosis accurately predicted optimal size range and correlated with in vitro results. The combination of folate conjugated AuNP with nanophotothermolysis treatment effectively destroyed cancer cells with little effect on normal cells demonstrating great potential for targeted cancer therapy.

Awards (1)

• First Place

Competition history

• CSEF 2011 Biochemistry/ Molecular Biology · Entry J0525

Resources

• CSEF project summary ↗

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