title: High drug loading and pH-responsive targeted nanocarriers from alginate-modified SPIONs for anti-tumor chemotherapy.
abstract: To increase the accumulation of nanocarriers at the tumor site and reduce premature drug leakage, we fabricated alginate modified superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic targeting capability for pH-responsive release of the anticancer drug doxorubicin (DOX) in tumor-cell microenvironments. The drug loading content (DLC) of SPION-4 was as high as 48.98% with a stable size of 135 nm, whereas the DLC of SPION-2 (amine-functionalized SPIONs as the control) was 7.58%. The in vitro release studies revealed that the acidic environment (pH 6.5 and pH 5.0) triggered the effective release of DOX from DOX-loaded SPION-4 twice and thrice as much as the neutral condition (pH 7.4) after 10.7 h, respectively. These nanocarriers exhibited good cytocompatibility towards both normal cells (LO2) and cancer cells (HepG2), but higher cytotoxicity against HepG2 cells for DOX-loaded SPION-4 than that against LO2 cells could be observed due to the effects of an additional magnet and the acidic microenvironment of cancer cells, which greatly improved the cellular uptake of magnetic nanoparticles and released more DOX in the cytoplasm and nucleus. The in vivo biodistribution and anti-tumor efficacy demonstrated that DOX-loaded SPION-4 under an external magnetic field could obviously increase the DOX concentration in tumor tissues to remarkably inhibit tumor growth and significantly reduce side effects of free DOX. Therefore, this work suggested that these SPION-4 nanoparticles may be a potential carrier to deliver chemotherapeutic agents in anti-tumor treatment.
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com and Guangzhou Sugarcane Industry Research Institute, Guangzhou, 510316, China.
authors: Na
authors: N
authors: Peng
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Bo
authors: B
authors: Wu
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Lei
authors: L
authors: Wang
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Weiyang
authors: W
authors: He
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Ziye
authors: Z
authors: Ai
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Xingjian
authors: X
authors: Zhang
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Yanfeng
authors: Y
authors: Wang
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com.
authors: Lin
authors: L
authors: Fan
authors: Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Disease of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China. yqf_china@163.com and The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, 410013, China.
authors: Qifa
authors: Q
authors: Ye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D001692:Biological Transport; D018929:Cell Culture Techniques; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D010316:Particle Size; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004317:Doxorubicin