title: Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: In vitro and in vivo evaluation.
abstract: In this study, we report the design and delivery of tumor-targeted, quantum dot (QD) and doxorubicin (DOX)-encapsulated PEG-PLGA nanopolymersomes (NPs) for the imaging and chemotherapy of breast cancer. To achieve active cancer targeting, QD and DOX-encapsulated NPs were conjugated with folate for folate-binding protein receptor-guided delivery, which overexpressed in many cancer cells. Hydrophobic DOX and hydrophilic MSA-capped QD were encapsulated in the bilayer and core of the PEG-PLGA nanopolymersomes, respectively. The data show that the formulated NPs sustained DOX release for a period of 12 days. Fluorescence microscopy and MTT assay demonstrated that the developed folate-targeted DOX-QD NPs had higher cytotoxicity than non-targeted NPs and the free form of the drug; moreover, they preferentially accumulated in 4T1 and MCF-7 cells in vitro. In vivo experiments including whole organ tissue-homogenate analysis and organ fluorescence microscopy imaging of BALB/c mice bearing 4T1 breast adenocarcinoma showed that the folate receptor-targeted QD encapsulated NPs accumulate at tumor sites 6h following intravenous injection. Acute toxicity studies of the prepared targeted QD-loaded NPs showed no evidence of long-term harmful histopathological and physiological effects on the treated animals. The in vivo tumor inhibitory effect of folic acid (FA)-QD-DOX NPs demonstrated an augmented therapeutic efficacy of targeted formulation over the non-targeted and free drug. The data obtained illustrate a high potential of the prepared targeted theranostic nanoplatform in the treatment and imaging of breast cancer. This study may open new directions for preparation of QD-based theranostic polymersomes for clinical application.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: mona.alibolandi@gmail.com.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sadeghi
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinkhani
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: hadizadehf@mums.ac.ir.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019187:Cadmium Compounds / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D058972:Folic Acid Transporters / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D041681:NIH 3T3 Cells; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045663:Quantum Dots / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D013691:Tellurium / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D019187:Cadmium Compounds; D058972:Folic Acid Transporters; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid; D013691:Tellurium; C028337:cadmium telluride
keywords: 4T1; Breast cancer; Doxorubicin; Nanopolymersome; PEG-PLGA; Quantum dot