Oxygenated theranostic nanoplatforms with intracellular agglomeration behavior for improving the treatment efficacy of hypoxic tumors

Zhou, Jun; Xue, Chencheng; Hou, Yanhua; Li, Menghuan; Hu, Yan; Chen, Qiufang; Li, Yanan; Li, Ké; Song, Guanbin; Cai, Kaiyong; Luo, Zhong

doi:10.1016/j.biomaterials.2019.01.002

Cited by 43 publications

(70 citation statements)

References 61 publications

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“… 21 , 45 , 46 In this application, PFCE–PLGA NPs made with the conventional batch method can act not just as imaging agents for 19 F MRI but also as multimodal imaging agents for ultrasound and optical methods. 9 , 22 , 24 On the therapeutic side, PFC-based colloids show promising results in the transportation of oxygen for the treatment of cancer 1 − 3 , 5 , 6 or stroke. 7 Therefore, in the current study, after basic toxicity testing, we focused on imaging applications and the oxygen loading in vitro .…”

Section: Resultsmentioning

confidence: 99%

Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic

Hoogendijk

Swider

Staal

et al. 2020

ACS Appl. Mater. Interfaces

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Perfluorocarbon-loaded nanoparticles are powerful theranostic agents, which are used in the therapy of cancer and stroke and as imaging agents for ultrasound and 19 F magnetic resonance imaging (MRI). Scaling up the production of perfluorocarbon-loaded nanoparticles is essential for clinical translation. However, it represents a major challenge as perfluorocarbons are hydrophobic and lipophobic. We developed a method for continuous-flow production of perfluorocarbon-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles using a modular microfluidic system, with sufficient yields for clinical use. We combined two slit interdigital micromixers with a sonication flow cell to achieve efficient mixing of three phases: liquid perfluorocarbon, PLGA in organic solvent, and aqueous surfactant solution. The production rate was at least 30 times higher than with the conventional formulation. The characteristics of nanoparticles can be adjusted by changing the flow rates and type of solvent, resulting in a high PFC loading of 20–60 wt % and radii below 200 nm. The nanoparticles are nontoxic, suitable for 19 F MRI and ultrasound imaging, and can dissolve oxygen. In vivo 19 F MRI with perfluoro-15-crown-5 ether-loaded nanoparticles showed similar biodistribution as nanoparticles made with the conventional method and a fast clearance from the organs. Overall, we developed a continuous, modular method for scaled-up production of perfluorocarbon-loaded nanoparticles that can be potentially adapted for the production of other multiphase systems. Thus, it will facilitate the clinical translation of theranostic agents in the future.

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Section: Resultsmentioning

confidence: 99%

Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic

Hoogendijk

Swider

Staal

et al. 2020

ACS Appl. Mater. Interfaces

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“…It has been approved by the Food and Drug Administration (FDA) as a blood substitute. [ 12a,27 ] Ren et al. loaded oxygenated PFC into hollow Bi 2 Se 3 nanoparticles followed by surface modification with GOx to construct a multifunctional nanoreactor (BGPO NPs, Figure ).…”

Section: Gox‐instructed Cancer Therapiesmentioning

confidence: 99%

Glucose Oxidase‐Related Cancer Therapies

Wang

Yang

Dong

et al. 2020

Advanced Therapeutics

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Glucose oxidase (GOx), which catalyzes the conversion of glucose into gluconic acid and hydrogen peroxide (H 2 O 2) in the presence of oxygen (O 2), has aroused growing interest for cancer therapy. GOx can starve tumor cells to death by depleting glucose, which is very important for their energy supply, and the generated H 2 O 2 is can be used for oxidation therapy. In addition, GOx-catalyzed glucose oxidation exerts a variety of effects on the tumor environment, such as enhancing hypoxia and increasing acidity. The full use of these characteristics can effectively reduce side effects and enhance the therapeutic efficiency of GOx-related cancer therapies. As is generally acknowledged, it is difficult to completely eliminate tumors with a single treatment, whereas combining two or more therapies may yield super-additive results because when properly designed, different treatments can compensate for the shortcomings of the other treatments and bring out the best in each other. In view of these facts, enhanced therapies and combination therapies related to glucose oxidation have been widely studied, and this review provides a systematic overview of recent research on GOx-related cancer therapies (especially starvation therapy) from the perspective of glucose oxidation (including the reaction itself, oxygen, enzymes, gluconic acid, and H 2 O 2) and other combination therapies.

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“…Zhou et al reported a PFC and etoposide (EP) co-loaded porous hollow Fe 3 O 4 nanoplatform (PHMNPs-S-S-PEG-LA@PFC/EP) with GSH-triggered agglomeration ability (Figure 9c). [342] With lactobionic acid (LA)-guided tumor targeting and improved intracellular retention by increasing agglomeration (Figure 9d,f), PHMNP-S-S-PEG-LA@PFC(O 2 )/ EP can alleviate tumor hypoxia ( Figure 9e) and improve EP's anti-cancer susceptibility, demonstrating the importance of intracellular retention of AHCNs. Similar to these examples, smart strategies need to be considered to prevent the exosmosis of AHCNs, and achieve comprehensive consideration of circulation, clearance, tumor accumulation, infiltration, retention, and other issues.…”

Section: Improving the Intracellular Retention Of Ahcnsmentioning

confidence: 99%

Retooling Cancer Nanotherapeutics’ Entry into Tumors to Alleviate Tumoral Hypoxia

Sun

et al. 2020

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The contribution of the TME in the progress of the malignant tumor is significant and now also increasingly recognized to affect the efficiencies of drug delivery and distribution within tumors. [8] Hypoxia is the phenomenon where the oxygen supplied through the usually aberrant tumor blood vessels are insufficient to consistently meet the growing tumor's metabolic needs. [9] Hypoxia occurs in tumors due to insufficient oxygen supply in relation to the tumors' metabolism and includes: a) acute hypoxia, the result of poor blood perfusion caused by abnormal, aberrant vasculature, giving rise to tortuous network organization, irregular flow pattern, [4] and b) chronic hypoxia, the cause and the result of a sparse vascular density in the tumor, giving rise to insufficient oxygen delivered to tumor cells spatially distant from blood vessels. Compensatory angiogenesis itself is also regarded as the result of mainly nutrient and oxygen deprivation as the tumor grows. [10] Hence, hypoxia is an element in the TME that is closely interconnected with pathological angiogenesis and extracellular matrix in cancer. In general, cells are sensitive to low oxygen conditions, which activate the hypoxia-inducible factor (HIF) family of transcriptional factors to allow for expression of genes that may enhance tumor survival under the hypoxic environment. One consequential outcome is the accumulation of vascular endothelial growth factor (VEGF) under transcription by HIF-1α, resulting in the induction of angiogenesis. [11] Under hypoxia, the oxygen-dependent subunit of HIF-1, HIF-1α, is successfully accumulated (otherwise degraded in normoxic conditions) to dimerize with an oxygen-independent subunit to form the HIF-1 dimer. [4] HIF-1 then upregulates dozens of genes that allows for both adaptation and long-term expansion of the tumor cells. [12] Hypoxia is a critical factor to examine, as there is increasing recognition of its role as a potential target during cancer therapy, although the dual role of HIFs in both promoting survival and apoptosis poses a challenge for certain tumor types and cases. [13] 1.2. Hypoxia Aggravates the Challenges for Cancer Therapy A major consequence of hypoxia is the occurrence of hypoxiainduced metastasis. Hypoxia and metastasis have been Anti-hypoxia cancer nanomedicine (AHCN) holds exciting potential in improving oxygen-dependent therapeutic efficiencies of malignant tumors. However, most studies regarding AHCN focus on optimizing structure and function of nanomaterials with presupposed successful entry into tumor cells. From such a traditional perspective, the main barrier that AHCN needs to overcome is mainly the tumor cell membrane. However, such an oversimplified perspective would neglect that real tumors have many biological, physiological, physical, and chemical defenses preventing the current state-of-the-art AHCNs from even reaching the targeted tumor cells. Fortunately, in recent years, some studies are beginning to intentionally focus on overcoming physiological barriers to alleviate hypoxi...

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Oxygenated theranostic nanoplatforms with intracellular agglomeration behavior for improving the treatment efficacy of hypoxic tumors

Cited by 43 publications

References 61 publications

Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic

Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic

Glucose Oxidase‐Related Cancer Therapies

Retooling Cancer Nanotherapeutics’ Entry into Tumors to Alleviate Tumoral Hypoxia

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