title: NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles.
abstract: The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore. cheliub@nus.edu.sg.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yuanzeng
authors.initials: Y
authors.lastname: Min
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Hu
authors.forename: Bengang
authors.initials: B
authors.lastname: Xing
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use; D008856:Microscopy, Fluorescence / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D058726:Nanoconjugates / Q000627:therapeutic use* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D053769:Nanocapsules; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D004317:Doxorubicin