Uniform TitleReceptor-targeted nanocarriers for tumor specific
treatment and imaging
NameSaad, Maha (author), Minko, Tamara (chair), You, G. (internal member), michniak, B. (internal member), Shahied, S. (outside member), Rutgers University, Graduate School - New Brunswick,
Drug delivery systems
DescriptionLung cancer is the leading cause of cancer death in the United States. The efficacy of chemotherapy in lung cancer is limited by the development of cancer cell resistance during the treatment, difficulties in the delivery of anticancer drugs specifically to lung tumors, and severe adverse side effects of high doses chemotherapy on healthy organs. The main objectives of the present research are: (1) to provide effective delivery of therapeutic and imaging agents to lungs, (2) to mitigate the above described resistance, (3) to enhance the efficacy of lung cancer chemotherapy and limit adverse side effects of the treatment. To achieve these goals, we developed, characterized, and evaluated in vitro and in vivo on orthotopic model of lung cancer using a novel multifunctional tumor-targeted Nanocarrier-based Drug Delivery System (NDDS) composed of (1) a carrier; (2) a synthetic analog of Luteinizing Hormone-Releasing Hormone (LHRH peptide) as a targeting moiety; (3) an anticancer drug or imaging agent; (4) suppressors of drug resistance. We tested and compared: linear polymer, dendrimers and liposomes as nanocarriers; antisense oligonucleotides or small interfering RNA targeted to MRP1 and BCL2 mRNA as suppressors of pump and nonpump cellular resistance respectively; near-infrared cyanine dye Cy5.5, rhodamine, or fluorescein isothiocyanate as imaging agents.
The proposed multivalent NDDS exhibited preferential accumulation in the lungs, increased the sensitivity and specificity of tumor imaging, enhanced cancer treatment, and limited adverse side effects of the treatment on healthy organs. Targeting of nanocarriers to tumor specific receptors minimizes the influence of the architecture, composition, size, and molecular mass of nanocarriers on the efficacy of imaging and cancer treatment.
Local intratracheal administration sustained higher concentration of NDDS and its payload in the lungs and substantially limited their accumulation in other organs. Moreover, intratracheal local delivery of NDDS led to the more efficient treatment of lung cancer when compared with the intravenous administration of NDDS or free drugs. Simultaneous suppression of pump and nonpump resistance dramatically enhanced the cytotoxicity of the anticancer drug leading to a substantial increase in apoptosis induction.
NoteIncludes bibliographical references.
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.