A Step‐by‐Step Multiple Stimuli‐Responsive Nanoplatform for Enhancing Combined Chemo‐Photodynamic Therapy

Wang, Yi; Wei, Guiwu; Zhang, Xiaobin; Xu, Funeng; Xiong, Xiang‐Yuan; Zhou, Shaobing

doi:10.1002/adma.201605357

Cited by 173 publications

(120 citation statements)

References 54 publications

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“…Our findings potentially allow inserting MRI into photomedicine for enhanced visualization. In addition, because a wide variety of free‐base porphyrins possess favorable properties for detection using CEST imaging, conjugation of these probes to water‐soluble polymers, liposomes, or incorporation into micelles should preserve the CEST properties, allowing their use for a wide variety of multimodal diagnostic and theranostic studies.…”

Section: Discussionmentioning

confidence: 99%

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Zhang

Yuan

et al. 2019

Magnetic Resonance in Med

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Purpose CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free‐base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection. Methods To test these newly identified CEST agents, we acquired a series of Z‐spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor‐bearing mice, and MR images were acquired to assess detection feasibility in vivo. Results Based on the Z‐spectra, the inner nitrogen protons in free‐base porphyrins and chlorin resonate from −8 to −13.5 ppm from water, far shifted from the majority of endogenous metabolites (0‐4 ppm) and Nuclear Overhauser enhancements (−1 to −3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5‐12 ppm). The exchange rates are sufficiently slow to intermediate (500‐9000 s−1) to allow robust detection and were sensitive to substituents on the porphyrin ring. Conclusion These results highlight the capabilities of free‐base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Zhang

Yuan

et al. 2019

Magnetic Resonance in Med

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“…Quantitative analysis of the fluorescence intensity and subcellular colocalization analysis were derived from those fluorescence images. Pearson's correlation coefficients (Rr) were utilized to quantitatively evaluate the correlation between the two types of fluorescence and also for the fluorescence colocalization analysis . A greater Rr value reflects a stronger correlation between the two fluorescent molecules, suggesting that the two molecules occur in the same space.…”

mentioning

confidence: 99%

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy

Wang

Wei

Zhang

et al. 2017

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Mitochondrial-targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin-loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core-shell-SS-shell architecture are composed of a core of Fe O colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near-infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment.

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“…Various reports consistently confirm that ROS could oxidize the lipids on cell membrane to increase its permeability, as well as those proteins on the membranes of endo/lysosomes to facilitate the subsequent release the entrapped nanoparticles into the cytosol, both of which hold promise for improving the delivery efficiency of nanoformulated drugs. A typical example of nanoformulations with PDT‐enhanced internalization and endo/lysosomal‐escaping capabilities was recently reported by Wang et al () In this study, the authors prepared a protoporphyrin‐based polymeric nanoplatform via self‐assembly mechanism, in which both the protoporphyrin IX (photosensitizer) and camptothecin (CPT) were grafted to the polymer backbone. Upon reaching the tumor tissues, the nanocarriers would be illuminated with red light for a short period to enhance the endocytosis efficiency, and the light treatment would also rupture the enso/lysosome membranes to accelerate cytosolic CPT release and help the CPT molecules reaching their nucleus targets.…”

Section: Patterns Of Treatment Cascadesmentioning

confidence: 97%

Cascade‐amplification of therapeutic efficacy: An emerging opportunity in cancer treatment

Luo

Peng

et al. 2019

WIREs Nanomed Nanobiotechnol

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Increasing research evidence reveals that cancer is complex disease involving many biological factors, processes and systems, which may severely limit the actual efficacy of conventional monotonic anticancer approaches. To overcome these obstacles in cancer treatment, a new strategy has been proposed by combining multiple synergistic therapeutic modalities accessing different but inherently related targets and acting sequentially. A major benefit of this strategy is that the multi‐target mechanism could result in a cascade‐amplification effect leading to enhanced anticancer activity. In this review, we provide a critical discussion on the application of cascade‐amplification strategy in the treatment of various cancer indications, focusing on the rational combination of therapeutic agents and their mechanisms of action. A concise yet comprehensive analysis on the potential therapeutic benefit of this strategy was also included. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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A Step‐by‐Step Multiple Stimuli‐Responsive Nanoplatform for Enhancing Combined Chemo‐Photodynamic Therapy

Cited by 173 publications

References 54 publications

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy

Cascade‐amplification of therapeutic efficacy: An emerging opportunity in cancer treatment

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