Core–Satellite Polydopamine–Gadolinium‐Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.

[1]  Jagadis Sankaranarayanan,et al.  An extracellular MRI polymeric contrast agent that degrades at physiological pH. , 2012, Molecular pharmaceutics.

[2]  Gang Liu,et al.  A Synergistically Enhanced T1–T2 Dual‐Modal Contrast Agent , 2012, Advanced materials.

[3]  Peng Huang,et al.  Graphene-based nanomaterials for bioimaging. , 2016, Advanced drug delivery reviews.

[4]  Kyung-Hwa Yoo,et al.  Convertible organic nanoparticles for near-infrared photothermal ablation of cancer cells. , 2011, Angewandte Chemie.

[5]  L. Zhen,et al.  Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells. , 2015, ACS applied materials & interfaces.

[6]  Ying Liu,et al.  Applications of Functionalized Fullerenes in Tumor Theranostics , 2012, Theranostics.

[7]  Jianru Xiao,et al.  Multi-responsive photothermal-chemotherapy with drug-loaded melanin-like nanoparticles for synergetic tumor ablation. , 2016, Biomaterials.

[8]  Mingjie Wu,et al.  Multifunctional Carbon-Based Nanomaterials: Applications in Biomolecular Imaging and Therapy , 2018, ACS omega.

[9]  Lehui Lu,et al.  Dopamine‐Melanin Colloidal Nanospheres: An Efficient Near‐Infrared Photothermal Therapeutic Agent for In Vivo Cancer Therapy , 2013, Advanced materials.

[10]  Liangzhu Feng,et al.  Near‐Infrared Absorbing Polymeric Nanoparticles as a Versatile Drug Carrier for Cancer Combination Therapy , 2013 .

[11]  Peng Huang,et al.  Multimodal‐Imaging‐Guided Cancer Phototherapy by Versatile Biomimetic Theranostics with UV and γ‐Irradiation Protection , 2016, Advanced materials.

[12]  Peng Huang,et al.  Dye‐Loaded Ferritin Nanocages for Multimodal Imaging and Photothermal Therapy , 2014, Advanced materials.

[13]  Ronghua Wang,et al.  NIR‐Laser‐Switched In Vivo Smart Nanocapsules for Synergic Photothermal and Chemotherapy of Tumors , 2016, Advanced materials.

[14]  Jie Yu,et al.  High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. , 2014, ACS nano.

[15]  Yongxiang Luo,et al.  Dual-Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy. , 2017, Small.

[16]  Tianfu Wang,et al.  Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications , 2016, Theranostics.

[17]  Chao Wang,et al.  An Imagable and Photothermal “Abraxane‐Like” Nanodrug for Combination Cancer Therapy to Treat Subcutaneous and Metastatic Breast Tumors , 2015, Advanced materials.

[18]  Sarah E Bohndiek,et al.  Contrast agents for molecular photoacoustic imaging , 2016, Nature Methods.

[19]  Zijian Zhou,et al.  Surface and interfacial engineering of iron oxide nanoplates for highly efficient magnetic resonance angiography. , 2015, ACS nano.

[20]  Liangzhu Feng,et al.  CaCO3 nanoparticles as an ultra-sensitive tumor-pH-responsive nanoplatform enabling real-time drug release monitoring and cancer combination therapy. , 2016, Biomaterials.

[21]  Yueqing Gu,et al.  Ratiometric Photoacoustic Molecular Imaging for Methylmercury Detection in Living Subjects , 2017, Advanced materials.

[22]  Liming Nie,et al.  Structural and functional photoacoustic molecular tomography aided by emerging contrast agents. , 2014, Chemical Society reviews.

[23]  Z. Gu,et al.  Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking , 2013, Theranostics.

[24]  Richey M. Davis,et al.  A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells. , 2015, Journal of the American Chemical Society.

[25]  Yuanyi Zheng,et al.  Injectable 2D MoS2‐Integrated Drug Delivering Implant for Highly Efficient NIR‐Triggered Synergistic Tumor Hyperthermia , 2015, Advanced materials.

[26]  Peng Huang,et al.  Biomineralization-Inspired Synthesis of Copper Sulfide-Ferritin Nanocages as Cancer Theranostics. , 2016, ACS nano.

[27]  R. Zhang,et al.  The degradation and clearance of Poly(N-hydroxypropyl-L-glutamine)-DTPA-Gd as a blood pool MRI contrast agent. , 2012, Biomaterials.

[28]  Peng Huang,et al.  Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy. , 2017, Biomaterials.

[29]  Kai Yang,et al.  Polydopamine as a Biocompatible Multifunctional Nanocarrier for Combined Radioisotope Therapy and Chemotherapy of Cancer , 2015 .

[30]  Wei Huang,et al.  Transferring Biomarker into Molecular Probe: Melanin Nanoparticle as a Naturally Active Platform for Multimodality Imaging , 2014, Journal of the American Chemical Society.

[31]  V. Muzykantov,et al.  Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities , 2012, Science.

[32]  Taeghwan Hyeon,et al.  Inorganic Nanoparticles for MRI Contrast Agents , 2009 .

[33]  D. Seidel Cinchona Alkaloids in Synthesis & Catalysis: Ligands, Immobilization and Organocatalysis Cinchona Alkaloids in Synthesis & Catalysis: Ligands, Immobilization and Organocatalysis . Edited by Choong Eui Song (Sungkyunkwan University, Suwon, Republik Korea). WILEY-VCH Verlag GmbH & Co. KGaA: Weinheim. , 2010 .

[34]  A. S. Moses,et al.  Imaging and drug delivery using theranostic nanoparticles. , 2010, Advanced drug delivery reviews.

[35]  Kai Yang,et al.  In Vitro and In Vivo Near‐Infrared Photothermal Therapy of Cancer Using Polypyrrole Organic Nanoparticles , 2012, Advanced materials.

[36]  Jiechao Ge,et al.  Multifunctional gadofulleride nanoprobe for magnetic resonance imaging/fluorescent dual modality molecular imaging and free radical scavenging , 2013 .

[37]  Kai Yang,et al.  FeSe2‐Decorated Bi2Se3 Nanosheets Fabricated via Cation Exchange for Chelator‐Free 64Cu‐Labeling and Multimodal Image‐Guided Photothermal‐Radiation Therapy , 2016, Advanced functional materials.

[38]  D. Parker,et al.  PEG-g-poly(GdDTPA-co-L-cystine): effect of PEG chain length on in vivo contrast enhancement in MRI. , 2005, Biomacromolecules.

[39]  Weibo Cai,et al.  Positron emission tomography imaging using radiolabeled inorganic nanomaterials. , 2015, Accounts of chemical research.

[40]  Jin Chang,et al.  Intrinsically Radioactive [64Cu]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence , 2014, ACS nano.

[41]  Weibo Cai,et al.  Dual-Modality Positron Emission Tomography/Optical Image-Guided Photodynamic Cancer Therapy with Chlorin e6-Containing Nanomicelles. , 2016, ACS nano.

[42]  Peng Huang,et al.  Marriage of Albumin-Gadolinium Complexes and MoS2 Nanoflakes as Cancer Theranostics for Dual-Modality Magnetic Resonance/Photoacoustic Imaging and Photothermal Therapy. , 2017, ACS applied materials & interfaces.

[43]  Liangzhu Feng,et al.  Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-guided Cancer Combination Therapy , 2016, Theranostics.

[44]  Changhui Li,et al.  Biocompatible polypyrrole nanoparticles as a novel organic photoacoustic contrast agent for deep tissue imaging. , 2013, Nanoscale.

[45]  S. Aime,et al.  Biodistribution of gadolinium‐based contrast agents, including gadolinium deposition , 2009, Journal of magnetic resonance imaging : JMRI.

[46]  H. Shinohara,et al.  Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents. , 2001, Bioconjugate chemistry.