Biocompatibility And Drug Loading Properties Of Hollow Mesoporous Silica Nanoparticles

In the past decades there is a growing trend in incidence of cancer. Various methods are used to cure cancer patients, including surgical operation, radiation treatment and chemotherapy, among which medication is of most significance. Current anticancer drug therapy results in systemic side effects due to nonspecific uptake by normal, healthy, noncancerous tissues. Traditional DDS involves capsule, liposome, dendrimer, hydrogel and so forth. They have many setbacks, such as non-target, premature drug release and uncontrolled drug release, which resulting in systemic side effects and inducing multidrug resistance. Therefore, it is urgent to develop more efficient drug delivery systems (DDS) that improve selective toxicities against cancer cells, resulting in an increase in the therapeutic indices of the anticancer drugs.Recently inorganic mesoporous materials as drug carriers received many interests around the world. They are able to delivery ibuprofen, gentamycin, captopril, camptothecin, serum albumin and so forth. And they can reduce side effects of drugs, prevent biodegradation of drugs in the gastrointestinal tract and enhance bioavailability of drugs. It is reported that nanoparticles could transport across the intestinal epithelium to get into the blood or circulatory system through lymphatic system, aiming at bringing the drugs to the targeted tissue to fulfill its task. Relying on the passive diffusion and dispersion to get access to the cancerous vasculature, nanoparticles could get into the body through intravenous injection, remain in the tissue space for a long time, and finally accumulate in the cancer cells. Hence it is possible to control the release of drugs inside the cancer tissue by using DDS.Hollow mesoporous silica nanoparticles (HMSN) was considered potential drug carriers as they have many advantages to load and release medicines through intravenous injection, such as high loading content, tunable pore size and high BET area. However, whether HMSN could exert cytotoxicity on vessel endothelial cells after intravenous injection still remained unknown. Additionally, are there many differences between the hollow mesoporous silica nanoparticles and solid silica? Mesoporous silica materials were thought to have thermal and chemical stability and are not apt to attacked by immune systems. However as drug carriers, whether HMSN could be degraded inside the cells and how they could get out of the body remained unknown. Whether HMSN could load anticancer drugs and enhance the cytotoxicity of drugs to the cancer cells still remained unknown.It was demonstrated that HMSN at the concentration more than 62.5μg/mL would exert cytotoxicity on HUVECs and the IC50 was about 150μg/mL. At high concentration HMSN significantly inhibited the proliferation of HUVECs, caused the release of LDH, arrested cell cycle at G1 period and eventually induced necrosis. The cytotoicity might come from the physical damage on cell structure by HMSN and chemical disturbance on metabolism caused by the product of HMSN degradation. Therefore, attentions should be paid on the single dosage, avoiding cytotoxicity to normal tissue vessels and stimulating cytotoxicity to tumor vessel.In this study it was demonstrated that HMSN could penetrate through the cell membrane into the cytoplasm of human umbilical vein endothelial cells, invade every organelle and degrade either in cytoplasm or in lysosomes. It was also demonstrated that HMSN could load doxorubicin and enhance the inhibition of doxorubicin to the breast cancer cells (MCF-7). It is implicated that as drug carriers, HMSN could release the medicines loaded while it was degraded completely. It was also found that HMSN could enhance the cytotoxicity of drugs, inducing further more inhibition of cancer cells.