Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers.
The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser.
Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China; Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Leyong
L
Zeng
Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China.
Yuanwei
Y
Pan
Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Ying
Y
Tian
Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Xin
X
Wang
Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China.
Wenzhi
W
Ren
Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Shouju
S
Wang
Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. Electronic address: cjr.luguangming@vip.163.com.
Guangming
G
Lu
Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China. Electronic address: aiguo@nimte.ac.cn.
Aiguo
A
Wu
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005459:Fluorides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007259:Infrared Rays; D061986:MCF-7 Cells; D008819:Mice, Nude; D053761:Nanocomposites / Q000627:therapeutic use / Q000648:ultrastructure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013932:Thulium / Q000493:pharmacokinetics / Q000627:therapeutic use; D014025:Titanium / Q000627:therapeutic use*; D015018:Ytterbium / Q000493:pharmacokinetics / Q000627:therapeutic use; D015019:Yttrium / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; C525362:sodium yttriumtetrafluoride; C009495:titanium dioxide; D015019:Yttrium; D004317:Doxorubicin; D013932:Thulium; D014025:Titanium; D015018:Ytterbium; D005459:Fluorides
Breast cancers; Enhanced chemotherapy; Multidrug resistance; NIR-triggered photodynamic therapy; NaYF(4):Yb/Tm–TiO(2) inorganic photosensitizers