Multifunctional hollow CaF2:Yb(3+)/Er(3+)/Mn(2+)-poly(2-Aminoethyl methacrylate) microspheres for Pt(IV) pro-drug delivery and tri-modal imaging.
Combining the multi-modal medical imaging with cancer therapy in one single system has attracted the great interests for theranostic purpose. In this paper, CaF2:Yb(3+)/Er(3+)/Mn(2+)-poly(2-Aminoethyl methacrylate) (UCHNs-PAMA) hybrid microspheres were successfully fabricated. The synthetic route to the nanocomposite based on a facile hydrothermal method for fabrication of hollow upconversion (UC) nanospheres at first and then post-ﬁlling the PAMA interiorly through photo-initiated polymerization. The UCHNs showed orange ﬂuorescence under 980 nm near infrared (NIR) laser excitation, which provided the upconverting luminescence (UCL) imaging modality. Meanwhile, the presence of functional Mn(2+) and Yb(3+) offered the enhanced T1-weighted magnetic resonance (MR) and computed tomography (CT) imaging, respectively. Thanks to introducing amine groups-containing PAMA inside the hollow nanospheres, the Pt(IV) pro-drug, c,c,t-Pt(NH3)2Cl2(OOCCH2CH2COOH)2 (DSP), can be conveniently bonded on the polymer network to construct a nanoscale anti-cancer drug carrier. The UCHNs-PAMA-Pt(IV) nanocomposite shows effective inhibition for Hela cell line via MTT assay. In contrast, Pt(IV) pro-drug and UCHNs-PAMA microspheres behave little cytotoxicity to Hela cells. This should be attributed the fact that the anti-cancer ability can be recovered only when Pt(IV) pro-drug was reduced to Pt(II)-drug in cellular environment. Furthermore, the in vivo experiments on small mice also confirm that the hybrid microspheres have relatively low toxic side effects and high tumor inhibition rate. These findings show that the multifunctional hybrid microspheres have potential to be used as UCL/MR/CT tri-modal imaging contrast agent and anti-cancer drug carriers.
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; University of Chinese Academy of Sciences, Beijing 100049, China.
Yunlu
Y
Dai
Department of Radiology, The Second Hospital of Jilin University, Changchun 130022, PR China.
Jianhua
J
Liu
College of Clinical Medicine, Jilin University, Changchun, Jilin 130012, PR China.
Ying
Y
Zhou
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Ping'an
P
Ma
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: zycheng@ciac.ac.cn.
Ziyong
Z
Cheng
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.
Yinyin
Y
Chen
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.
Xuejiao
X
Li
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.
Chunxia
C
Li
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; D002124:Calcium Fluoride / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004871:Erbium / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D049449:Luminescence; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D008863:Microspheres; D064847:Multimodal Imaging; D054118:Nanospheres / Q000648:ultrastructure; D010984:Platinum / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D013696:Temperature; D014057:Tomography, X-Ray Computed; D015018:Ytterbium / Q000737:chemistry*
D008689:Methacrylates; D011355:Prodrugs; D008345:Manganese; D010984:Platinum; C072703:2-aminoethylmethacrylate; D004871:Erbium; D015018:Ytterbium; D002124:Calcium Fluoride
CaF(2):Yb(3+)/Er(3+)/Mn(2+); Drug delivery; Hollow microspheres; MRI/UCL/CT imaging; Poly(2-Aminoethyl methacrylate)