Research

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Nanoparticles have emerged as an important nanomaterial for cancer therapy. These particles specifically accumulate in tumor and prevent non-specific distribution of anticancer drugs throughout the body thus contributing significantly to reduced side effect of chemotherapy. Over the years, we have developed mesoporous silica nanoparticles (MSN) for tumor targeting nanoparticles. Recently, we have developed a novel type of MSN that contains biodegradable bonds within the framework of nanoparticles. We have also found that these nanoparticles show excellent drug delivery capability.

We made use of the chicken egg tumor model, an attractive system utilizing fertilized chicken eggs for growing human cancer cell xenograft. The system was established using human ovarian cancer cells expressing GFP. Intravenous injection of doxorubicin results in tumor apoptosis and disappearance of tumor, but excess injection causes other organ damages. However, this side effect could be overcome by loading doxorubicin onto the nanoparticle. In addition, we observed accumulation of doxorubicin to the tumor by red fluorescence. These results point to the advantage of using nanoparticles to prevent side effect of chemotherapy.

A: Mesoporous silica nanoparticles for cancer therapy

1. Mesoporous silica nanoparticles (MSN)

We are making mesoporous silica nanoparticles that have diameter in the range of 50-300 nm and that contain thousands of pores. The pore provides a space for storing anticancer drugs such as doxorubicin, camptothecin and taxol. MSN is taken up efficiently into human cancer cells and delivery anticancer drugs. Our mouse experiments demonstrated the ability of MSN to inhibit tumor growth. MSN can also carry siRNA to inhibit gene expression. Inhibition of the TWIST gene in an ovarian cancer mouse model led to tumor inhibition and restoration of drug sensitivity.

2. Biodegradability

We are making modification to MSN so that biodegradable character can be incorporated into MSN (in collaboration with Dr. Niveen Khashab, King Abdulah University of Science and Technology, and Dr. Jean-Olivier Durand, University of Montpellier). These nanoparticles called biodegradable PMO contain biodegradable bonds such as peptide bond and disulfide bond within the framework of the nanoparticle. These nanoparticles are easily taken up into cancer cells and deliver anticancer drugs.

B: The chicken egg tumor model as a versatile model for characterizing novel nanomaterials and anticancer drugs

1. The CAM membrane

To characterize novel nanoparticles, we are using the chicken egg tumor model that is established by transplanting human cancer cells onto the chorioallantoic membrane (CAM) that surrounds embryo inside a fertilized egg. Due to its undeveloped immune system and presence of a highly vascularized structure, tumor is formed in three days. Interestingly, the tumor formed contain vasculature, extracellular matrix and stromal cells closely resembling human tumor.

2. Characterization of anticancer drugs

Anticancer drugs can be evaluated by injecting intravenously and examining tumor. When we injected doxorubicin, we could observe tumor shrinkage and the tumor eventually disappeared. This is presumably due to apoptosis induction by doxorubicin.

When doxorubicin is loaded onto nanoparticles (MSN), we were able to inject much higher amount compared to the free drug. Organs in the embryo appeared normal and the eggs survived. This contrasted with situation when free drug was injected, as multiple organ damage was observed when free doxorubicin was injected.

3. Patient derived tumor model

Recently, we have succeeded in establishing tumor in this model by using tumor samples from ovarian cancer patients. In collaboration with scientists at the City of Hope Cancer Center, we have established tumor in the chicken egg and successfully treated it with doxorubicin and cisplatin. Thus, the chicken egg model can be used to characterize tumor from ovarian cancer patients.

Tumor tissue from ovarian cancer patient was minced and placed on CAM fromVu et al (2018) Scientific Reports 8, 8524.

C. Boron Neutron Capture Therapy (BNCT)

A type of radiation therapy for cancer. The boron accumulates in tumor cells after injection into a blood vessel. After that, the patient receives radiation therapy with neutron by using a nuclear reactor. The neutron hit the boron without harming normal cells, and it separates 4He (αray) and 7Li. This αray injury the DNA of cancer cells. Our group succeed the specifically accumulation of boron in the tumor by using MSNs which has high tumor targeting capability. This achievement might improve the BNCT.


1. Cancer Establishment

2. Accumulation of 10BPA-MSNs

10BPA-MSNs specifically accumulate inside cancer cells because that has high tumor targeting capability.

3. Neutron Irradiation

Neutron irradiated.

4. Cancer Cell Elimination by BNCT

BNCT could eliminated cancer cells, specifically.

D. Auger effect and DNA breaks


We have been developing a new type of radiation therapy, using nanoparticles that contain iodine or gadolinium. When these nanoparticles were taken up into cancer cells, tumor cells can be destroyed by X-ray with a defined energy. The destruction involves release of electrons that cause double strand DNA breaks. This approach, called auger therapy, is based on photoelectron effect described by Albert Einstein in 1905. This method may be effective so that we can damage center of tumors, which have been difficult to kill due to low oxygen level.

Fig. 1 Auger effect

It is known that in photoelectron effect, series of reactions happen and many electrons are released. When an electron at the K-edge absorb X-ray energy and is kicked out, an electron at an outer shell moves to the K-shell to stabilize the atom. At this time, another electron which receive the released energy is released out of the atom. The released electrons are called auger electrons. Auger electrons are released when monochromatic X-rays are irradiated onto high Z elements.

Fig. 2 DNA strand breaks by auger effect

When X-rays are irradiated onto tumor tissue loaded with iodine-containing nanoparticles, the iodine releases electrons that break DNA and kill the cancer cells.