| Breast cancer is the most common cancer in female and most of them are advanced breast cancer in clinical. Chemotherapy is still one of the most common method of therapy. However, the chemotherapy drugs not only kill tumor cells but also seriously affect the body’s normal cells. Development of novel targeting and combination therapy drug carriers is promising to solve this problem of breast cancer. Targeting drug delivery system with "zero-premature release" of the toxic pharmaceutical cargo in the circulation to decrease the side effect. Mesoporous silica nanoparticles (MSNs) based controlled-release drug carriers have attracted more and more attention because of their good mechanical stability, high drug loading capacity, excellent biocompatibility, and easily modified surface. We designed two stilumi responsive drug delivery systems and studied drug release properties in vitro and therapuetic effect of breast cancer cell,includig the following aspects:1. Cytochrome C capped MSNs for pH-sensitive and sustained drug releaseA pH-responsive drug nanocarrier based on MSNs capped with a natural, nontoxic protein Cytochrome C (CytC) is designed and demonstrated for cancer therapy. At neutral pH the positively charged CytC can prevent the premature release of preloaded anti-cancer drug. The results show that the CytC capped nanocarriers have excellent doxorubicin (Dox) loading efficiency (414 μg/mg MSN) and the leakage of the drug is only 16% at pH 7.4 phosphate-buffered saline for 72 h. Simultaneously, Dox release percentage can reach 54% by decreasing pH to 5.5. In contrast, unsealed MSNs show a fast DOX release rate at pH 7.4 and a slight pH-response. Confocal laser scanning microscopy demonstrates that the nanocarriers can enter human breast cancer MCF-7 cells and the DOX is sustained released from the drug carriers.Cytotoxicity tests and histological assays confirm that the constructed CytC capped nanocarriers possess lower toxicity than free Dox and unsealed drug carriers. Furthermore, intratumoral administration of the nanocarriers is significantly more efficacious in tumor reduction than free DOX and unsealed drug carriers in the xenograft models of MCF-7 cancers. Overall, this study demonstrates new drug nanocarriers with pH-sensitive and sustained drug release properties by using natural and nontoxic protein as pore blocker to achieve highly efficient cancer treatment.2. Aptamer-Targeting Photoresponsive Drug Delivery System Using "Off-On" Graphene Oxide Wrapped MSNsA novel aptamer-targeting photoresponsive drug delivery system was constructed by non-covalent assembly of Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The MSN-Dox@GO-Apt with two "off-on" switches were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting ability and real-time indicator by "off-on" Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When GO wrapping falls off upon laser irradiation, the "off-on" photoresponsive drug delivery system is activated, thus inducing chemotherapy. Interestingly, with the increase of laser power, the synergism of chemotherapy and photothermal therapy in a single MSN-Dox@GO-Apt platform led to much more effective cancer cell killing than monotherapies, providing a new arsenal against cancer. |
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