Design And Preparation Of Mesoporous Hollow Drug Carrier And Its Application In Micro / Noninvasive Therapy

Since the currently wide used cancer treatment modalities(chemotherapy and radiotherapy) have some inevitable shortcomings and side effects, minimal/non-invasive tumor-treatment philosophy and therapeutic methods have received much more attention. High intensity focused ultrasound(HIFU) and photothermal therapy(PTT) are the two typically minimal/non-invasive treatment methods, i.e., by the use of external stimuli(sound or light) advantage, causing lesions tissue burning and necrosis, without toxic and side effects on normal tissues. Hollow mesoporous materials with large cavity, high pore volume and excellent biocompatibility, etc., can load a large amount of drugs and guest molecules, which have attracted much interest of the majority researchers in the diagnosis and treatment of cancer. This research work focuses on functional design and preparation of the hollow mesoporous silica nanoparticles(HMSN) and hollow mesoporous Prussian blue(HPB), and exploring the possible application in the minimal/non-invasive tumor treatments, as follows:(1) HIFU mediated drug controlled release and efficiently synergistic tumor treatment using hollow mesoporous silica nanocomposite as carrier. In this chapter, a novel phospholipid-modified hollow mesoporous silica nanoparticle(LHMSN) was designed and synthesized, which has large surface area(807 m2/g) and cavity and high drug-loading rate(DOX: 43.5%, CPT: 19.3%). The stability of LHMSN has been improved after successful modification of phospholipids. Both the anticancer drug and a kind of triphase(solid- liquid- gas) change compound, temperature-sensitive L-menthol(LM) have been co-loaded into the LHMSN carrier. Upon HIFU stimulation, the instant high-strength mechanical action could crush and destroy LHMSN to some extent, beneficial to controlled release of drug and the phase transition of LM, also the degradation of carrier material. Both in vitro and in vivo results confirm the excellent treatment efficacy by using this nanosystem.(2) Perfluoropentane-encapsulated hollow mesoporous prussian blue nanocubes for activated ultrasound imaging and photothermal therapy of cancerHollow mesoporous nanomaterials have gained tremendous attention in the fields of nanomedicine and nanobiotechnology. Herein, n-perfluoropentane(PFP)-encapsulated hollow mesoporous Prussian Blue(HPB) nanocubes(HPB-PFP) with excellent colloidal stability have been synthesized for concurrently in vivo tumor diagnosis and regression. The HPB shell shows excellent photothermal-conversion efficiency that can absorb the near-infrared(NIR) laser and convert it into heat. The generated heat can not only cause tumor ablation by raising the temperature of tumor tissue, but also promote the continuous gasifying and bubbling of encapsulated liquid PFP with low boiling point. The formed PFP bubbles can cause tissue impedance mismatch, thus apparently enhancing the signal of B-mode ultrasound imaging in vitro and generating apparent echogenicity signal for tumor tissues of nude mice in vivo. Without showing observable in vitro and in vivo cytotoxicity, the designed biocompatible HPB-PFP nanotheranostics with high colloidal stability and photothermal efficiency are anticipated to find various biomedical applications in activated ultrasound imaging-guided tumor detection and therapy.