Synthesis Of Multifunctional Anticancer Nanodrugs And Their Applications In Cancer Therapy

In this thesis, we have studied the aspect ratio(AR) effect of drug nanocrystals and developed a multifunction nanoparticle for cancer therapy. The results are listed as follows:1. HCPT NCs with four different ARs were controllably developed, which exhibited a strong AR dependent on cellular internalizing efficiency, uptake mechanisms,biodistributions as well as in vitro and in vivo anticancer efficiency. Shorter HCPT NCs(AR=1.3) showed obviously enhanced internalization rates than the longer NCs(AR=2.0, 3.2 and 4.0), which maybe a benefit from the fact that shorter NCs possess much larger surface areas in contact with the cell membrane than the longer ones. In vitro cytotoxicity experiments showed that shorter NCs exhibited a higher toxicity. In vivo experiments showed that NCs with AR=4.0 had a shortest half-life blood circulation time and were more easily captured by the liver, while NCs with the smallest AR possessed the highest therapeutic efficacy with appreciably less weight loss. These results indicate that aspect ratio is an important parameter which have a significantly effect on drug efficiency, and which would assist in the future design of drug nanocrystals in bioapplications.2. We have synthesized MFALPM nanoparticles(NPs) based on methotrexate(MTX) nanocore, Fe3O4 magnetic(NPs), gold nanoshells and LA-PEG-MTX coated as a multifunctional platform to combine magnetic and active-targeted drug delivery, MR imaging, NIR light-triggered drug release, and photothermal therapy into one system simultaneously. The resulting MFALPM NPs display surface plasmon absorbance in the NIR region, thus exhibiting an NIR-induced temperature elevation and an NIRlight-triggered release behavior of MTX. In vitro studies indicate a synergistic effect in killing cancer cells by the combined chemo-photothermal therapy and the magnetic and MTX-targeted drug delivery. In vivo biodistribution studies show that the NPs have a high accumulation at the tumor site by the magnetic targeting, which can be further used in in vivo cancer therapy. In vivo studies indicate that the NPs have a light triggered drug release behavior and an efficient chemo-photothermal effects which result in 100%in vivo tumor elimination without tumor recurrence. In vivo MR imaging of tumor-bearing mice is also demonstrated using MFALPM NPs as the T2 contrast agent.Moreover, no obvious systematic toxicity is observed of the mice after injection of MFGLPM NPs, indicating the good biocompatibility. The “all-in-one” drug delivery system, which combines all of the functional units into one nanoparticle with built-in capabilities for triggerable fast-response and combined hyperthermia chemotherapy are expected to open a new avenue for cancer treatment, possibly leading to clinical applications.