808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd(3+)-sensitized upconversion emission with enhanced anti-tumor efficacy.
The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd(3+)-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
Zhiyao
Z
Hou
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Kerong
K
Deng
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. Electronic address: cxli@ciac.ac.cn.
Chunxia
C
Li
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Xiaoran
X
Deng
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
Hongzhou
H
Lian
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
Ziyong
Z
Cheng
Institute for Biomedical Materials and Devices, Faculty of Science, University of Techology Sydney, NSW, 2007, Australia.
Dayong
D
Jin
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. Electronic address: jlin@ciac.ac.cn.
Jun
J
Lin
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D005459:Fluorides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009354:Neodymium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019800:Phenol; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014466:Ultraviolet Rays; D015019:Yttrium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D017319:Photosensitizing Agents; D011809:Quinones; D017382:Reactive Oxygen Species; C525362:sodium yttriumtetrafluoride; C009495:titanium dioxide; D009354:Neodymium; D019800:Phenol; D015019:Yttrium; D010569:Perylene; D006820:Hyaluronic Acid; D014025:Titanium; D005459:Fluorides; C048388:hypocrellin A
808 nm light; Dual-photosensitizers nanoplatform; Hyaluronic acid target; Nd(3+)-sensitized upconversion nanoparticles; Photodynamic therapy