Activatable Cell-Penetrating Peptide Conjugated Polymeric Nanoparticles with Gd-Chelation and Aggregation-Induced Emission for Bimodal MR and Fluorescence Imaging of Tumors

Xia, Bin; Xu, Yan; Fang, Wei; Chen, Sheng; Jiang, Zhilin; Wang, JinChen; Sun, Tian-Ci; Li, Qing; Li, Zhen; Lu, Yang; He, Tao; Cao, Baoqiang; Yang, Chang‐Tong

doi:10.1021/acsabm.9b01049

Cited by 13 publications

(13 citation statements)

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“…Chelate stability of Gd 3+ in SPIO@PEG-GdDTPA was evaluated by the absorption of Gd-arsenazo III complex referring previously reported method [ 32–34 ]. Briefly, equal molar ratio of arsenazo III solution (ASIII, 5 × 10 −5 M) and Gd 3+ in SPIO@PEG-GdDTPA was mixed, and then the absorbance spectra were measured using an UV-vis spectrophotometer (U-3900, Hitachi) at 660 nm.…”

Section: Methodsmentioning

confidence: 99%

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T1–T2 dual-mode magnetic resonance imaging probes

Yang

Cai

et al. 2021

Regenerative Biomaterials

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The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.

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Section: Methodsmentioning

confidence: 99%

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T1–T2 dual-mode magnetic resonance imaging probes

Yang

Cai

et al. 2021

Regenerative Biomaterials

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“…C,D) Reproduced with permission. [45] Copyright 2020, American Chemical Society. theranostic systems combining diagnostic imaging to monitor the therapeutic process or visualize specific locations.…”

Section: Aie-active Nanotheranostics Assembled From Small Aie Moleculesmentioning

confidence: 99%

“…C) Fluorescence inverted microscope images of HepG2 and D) fluorescence images of HepG2‐tumor‐bearing mice after intravenous or injection of N‐BP5‐Gd‐ACPPs and N‐BP5‐Gd, respectively. C,D) Reproduced with permission [45 . ] Copyright 2020, American Chemical Society.…”

Section: Supramolecular Self‐assembly Of Aiegensmentioning

confidence: 99%

“…Gadolinium (Gd)‐chelating and AIE‐active polymeric nanoparticles (N‐BP5‐Gd‐ACPPs), conjugated with activatable cell‐penetrating peptides (ACPPs), were successfully designed and utilized in MRI and FLI for tumor diagnosis. [ 45 ] ACPPs within N‐BP5‐Gd‐ACPPs were cleaved to release polycation which facilitated the nanoparticles to penetrate HepG2 cells. This was confirmed by in vitro FLI (Figure 4C).…”

Section: Supramolecular Self‐assembly Of Aiegensmentioning

confidence: 99%

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Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

et al. 2020

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health concerns across the world. [1] Particularly significant is the effort directed toward the treatment of cancer, which has remained as one of the leading causes of rapidly growing morbidity and mortality rates for centuries. Among a number of significant advances achieved in this domain, cancer theranostics is one such advancement that allows the ingenious integration of accurate diagnosis with therapeutic intervention in a single formulation within spatial colocalization. This phenomenon has captivated the interest of researchers for the evaluation of the potential in fundamental studies and clinical application, [2] primarily due to the attribution of various intrinsic advantages to theranostics, including maximized therapeutic efficacy, optimized drug safety, and improved pharmacokinetics. [3] Notably, in comparison with the conventional therapeutic methods for cancers such as surgical removal, chemotherapy, and radiotherapy, [4] theranostics involves some burgeoning therapeutic strategies including photothermal therapy (PTT), [5] photodynamic therapy (PDT), [6] and gene therapy. It has become one of the most intensive areas of research during recent years due to high efficiency, minimal side effects, excellent tumor suppression, and non-invasive conversion. One of the major pursuits of biomedical science is to develop advanced strategies for theranostics, which is expected to be an effective approach for achieving the transition from conventional medicine to precision medicine. Supramolecular assembly can serve as a powerful tool in the development of nanotheranostics with accurate imaging of tumors and real-time monitoring of the therapeutic process upon the incorporation of aggregation-induced emission (AIE) ability. AIE luminogens (AIEgens) will not only enable fluorescence imaging but will also aid in improving the efficacy of therapies. Furthermore, the fluorescent signals and therapeutic performance of these nanomaterials can be manipulated precisely owing to the reversible and stimuli-responsive characteristics of the supramolecular systems. Inspired by rapid advances in this field, recent research conducted on nanotheranostics with the AIE effect based on supramolecular assembly is summarized. Here, three representative strategies for supramolecular nanomaterials are presented as follows: a) supramolecular self-assembly of AIEgens, b) the loading of AIEgens within nanocarriers with supramolecular assembly, and c) supramolecular macrocycle-guided assembly via host-guest interactions. Meanwhile, the diverse applications of such nanomaterials in diagnostics and therapeutics have also been discussed in detail. Finally, the challenges of this field are listed in this review.

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“…Similarly, ACPPs have been conjugated with Gd-DO3A, oligo (ethylene glycol), methyl ether methacrylate (OEGMA), and AIEgens TPEE (2-[4-vinylphenyl-1,1,2-triyl] tribenzene) that emits strong fluorescence ( Xia et al, 2020 ). This nanosystem, named N-BP5-Gd-ACPPs, has a size of ∼40 nm in which the hydrophobic AIEgens TPEE constitutes the core, hydrophilic copolymers P(OEGMA-co-Gd-DO3A) form the shell, and ACPPs compose the corona.…”

Section: Matrix Metalloproteinases’ Contribution To Cancer Diagnosis ...mentioning

confidence: 99%

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment

González-Ávila

Sommer²,

García-Hernández³

et al. 2022

Front. Mol. Biosci.

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Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs’ augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhibitors have been created to block MMPs’ enzymatic activity. However, they have been ineffective in addition to causing considerable side effects. On the other hand, nanotechnology offers the opportunity to formulate therapeutic agents that can act directly on a target cell, avoiding side effects and improving the diagnosis, follow-up, and treatment of cancer. The goal of the present review is to discuss novel nanotechnological strategies in which MMPs are used with theranostic purposes and as therapeutic targets to control cancer progression.

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Activatable Cell-Penetrating Peptide Conjugated Polymeric Nanoparticles with Gd-Chelation and Aggregation-Induced Emission for Bimodal MR and Fluorescence Imaging of Tumors

Cited by 13 publications

References 68 publications

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T1–T2 dual-mode magnetic resonance imaging probes

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T1–T2 dual-mode magnetic resonance imaging probes

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment

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