title: A PEGylation-Free Biomimetic Porphyrin Nanoplatform for Personalized Cancer Theranostics.
abstract: PEGylation (PEG) is the most commonly adopted strategy to prolong nanoparticles' vascular circulation by mitigating the reticuloendothelial system uptake. However, there remain many concerns in regards to its immunogenicity, targeting efficiency, etc., which inspires pursuit of alternate, non-PEGylated systems. We introduced here a PEG-free, porphyrin-based ultrasmall nanostructure mimicking nature lipoproteins, termed PLP, that integrates multiple imaging and therapeutic functionalities, including positron emission tomography (PET) imaging, near-infrared (NIR) fluorescence imaging and photodynamic therapy (PDT). With an engineered lipoprotein-mimicking structure, PLP is highly stable in the blood circulation, resulting in favorable pharmacokinetics and biodistribution without the need of PEG. The prompt tumor intracellular trafficking of PLP allows for rapid nanostructure dissociation upon tumor accumulation to release monomeric porphyrins to efficiently generate fluorescence and photodynamic reactivity, which are highly silenced in intact PLP, thus providing an activatable mechanism for low-background NIR fluorescence imaging and tumor-selective PDT. Its intrinsic copper-64 labeling feature allows for noninvasive PET imaging of PLP delivery and quantitative assessment of drug distribution. Using a clinically relevant glioblastoma multiforme model, we demonstrated that PLP enabled accurate delineation of tumor from surrounding healthy brain at size less than 1 mm, exhibiting the potential for intraoperative fluorescence-guided surgery and tumor-selective PDT. Furthermore, we demonstrated the general applicability of PLP for sensitive and accurate detection of primary and metastatic tumors in other clinically relevant animal models. Therefore, PLP offers a biomimetic theranostic nanoplatform for pretreatment stratification using PET and NIR fluorescence imaging and for further customized cancer management via imaging-guided surgery, PDT, or/and potential chemotherapy.
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.|‡Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 2J7, Canada.|§Medical Isotopes Research Center, Peking University, Beijing 100871, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Cui
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Qiaoya
authors.initials: Q
authors.lastname: Lin
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.|∥Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2J7, Canada.|#Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
authors.forename: Cheng S
authors.initials: CS
authors.lastname: Jin
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Wenlei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.|∇Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
authors.forename: Nidal
authors.initials: N
authors.lastname: Muhanna
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.|∇Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Irish
authors.affiliation: §Medical Isotopes Research Center, Peking University, Beijing 100871, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: †Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada.|‡Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 2J7, Canada.|∥Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2J7, Canada.|#Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D061848:Optical Imaging; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D057285:Precision Medicine / Q000379:methods*; D017433:Protein Structure, Secondary; D025321:Surgery, Computer-Assisted; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D016632:Apolipoprotein A-I; D011166:Porphyrins
keywords: PEGylation; PET imaging; fluorescence-guided surgery; multimodal imaging; nanoparticle; photodynamic therapy; porphyrin