title: A quantum dot-MUC1 aptamer conjugate for targeted delivery of protoporphyrin IX and specific photokilling of cancer cells through ROS generation.
abstract: Non-targeted photosensitizers lack selectivity that undermines the potential use of photodynamic therapy (PDT). Herein, we report the DNA mediated assembly of a ZnSe/ZnS quantum dot (QD)-photosensitizer (PS)-Mucin 1(MUC1) aptamer conjugate for targeting the MUC1 cancer biomarker and simultaneous generation of reactive oxygen species (ROS). A photosensitizer, protoporphyrin IX (PpIX), was conjugated to a single stranded DNA and self-assembled to a complementary strand that was conjugated to a QD and harboring a MUC1 aptamer sequence. A multistep fluorescence resonance energy transfer (FRET) is shown that involves the QD, PpIX and covalently linked CF™ 633 amine dye (CF dye) to the MUC1 peptide that tracks the potency of the aptamer to attach itself with the MUC1 peptide. Since the absorption spectra of the CF dye overlap with the emission spectra of PpIX, the former acts as an acceptor to PpIX forming a second FRET pair when the dye labeled MUC1 binds to the aptamer. The binding of the QD-PpIX nanoassemblies with MUC1 through the aptamer was further confirmed by gel electrophoresis and circular dichroism studies. The selective photodamage of MUC1 expressing HeLa cervical cancer cells through ROS generation in the presence of the QD-PpIX FRET probe upon irradiation is successfully demonstrated.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India. prolay@iitp.ac.in.
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Hajipur 844101, Bihar, India.
authors.forename: Pravin
authors.initials: P
authors.lastname: Jha
authors.affiliation: Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India. prolay@iitp.ac.in.
authors.forename: Vandana
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Hajipur 844101, Bihar, India.
authors.forename: Kislay
authors.initials: K
authors.lastname: Sinha
authors.affiliation: Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India. prolay@iitp.ac.in.
authors.forename: Sahid
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Atomic and Molecular Physics Division, Bhabha Atomic Research Centre, Mumbai 400085, India. mksingh@barc.gov.in singh_manojk@yahoo.com.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India. prolay@iitp.ac.in.
authors.forename: Prolay
authors.initials: P
authors.lastname: Das
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry; D045663:Quantum Dots; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D052157:Aptamers, Nucleotide; D053769:Nanocapsules; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C028025:protoporphyrin IX