Feasibility study of dual-targeting paclitaxel-loaded magnetic liposomes using electromagnetic actuation and macrophages

Nguyen, Van Du; Han, Jiwon; Go, Gwangjun; Jin, Zhen; Zheng, Shaohui; Le, Viet Ha; Park, Jong-Oh; Park, Sukho

doi:10.1016/j.snb.2016.09.076

Cited by 38 publications

(37 citation statements)

References 27 publications

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“…To our knowledge, this study represents the first report of reprogramming of monocytes for sustained maintenance of macrophage phenotype without genetic modification. Taken together with studies that have shown that macrophages can deliver drugs to sites of interest 52,53 , our findings suggest that microparticle-loaded monocytes hold considerable potential as a cell therapy strategy across a wide range of applications.…”

Section: Discussionsupporting

confidence: 67%

“…Moreover, we chose dexamethasone for proof of concept, but a drug that promotes a more regenerative macrophage phenotype would be a better choice for studying therapeutic efficacy. Finally, within this paper we have not characterized the effect of microparticle-loading on the homing capacity of monocytes, although other groups have completed similar characterizations 52,53,62 , but this will be important if monocytes are to be administered systemically.…”

Section: Discussionmentioning

confidence: 99%

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Non-Genetic Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype

Wofford

Singh

Cullen

et al. 2019

Preprint

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Monocyte-derived macrophages orchestrate tissue regeneration by homing to sites of injury, phagocytosing pathological debris, and stimulating other cell types to repair the tissue. Accordingly, monocytes have been investigated as a translational and potent source for cell therapy, but their utility has been hampered by their rapid acquisition of a pro-inflammatory phenotype in response to the inflammatory injury microenvironment. To overcome this problem, we designed a cell therapy strategy where we collect and exogenously reprogram monocytes by intracellularly loading the cells with biodegradable microparticles containing an anti-inflammatory drug in order to modulate and maintain an anti-inflammatory phenotype over time. To test this concept, poly(lactic-co-glycolic) acid microparticles were loaded with the anti-inflammatory drug dexamethasone (Dex) and administered to primary human monocytes for four hours to facilitate phagocytic uptake. After removal of non-phagocytosed microparticles, microparticle-loaded monocytes differentiated into macrophages and stored the microparticles intracellularly for several weeks in vitro, releasing drug into the extracellular environment over time. Cells loaded with intracellular Dex microparticles showed decreased expression and secretion of inflammatory factors even in the presence of pro-inflammatory stimuli up to 7 days after microparticle uptake compared to untreated cells or cells loaded with blank microparticles. This study represents a new strategy for long-term maintenance of anti-inflammatory macrophage phenotype using a translational monocyte-based cell therapy strategy without the use of genetic modification. Because of the ubiquitous nature of monocytederived macrophage involvement in pathology and regeneration, this strategy holds potential as a treatment for a vast number of diseases and disorders. RESULTS Microparticle Characteristics and Intracellular StabilityPoly(lactic-co-glycolic) acid (PLGA) microparticles were fabricated with dexamethasone (Dex) or with tetramethylrhodamine (TRITC) as a fluorescent model drug. Microparticles ranged in diameter from 0.98 to 2.05 µm with polydispersity indices between 0.08 and 0.28 ( Fig. 2A).Microparticles were administered to primary human monocytes for 4 hours followed by removal of non-phagocytosed microparticles. Thereafter, monocytes were cultured in macrophage colony stimulating factor (MCSF)-containing media to induce differentiation into macrophages and were imaged at regular intervals (Fig. 2B). Cell area increased over time for both untreated and microparticle-loaded cells, indicating that that monocyte-to-macrophage differentiation was not hindered by intracellular microparticle loading (Fig. 2C). Intracellular fluorescent microparticles were detected for up to 16 days in vitro (detection and quantification methods outlined in Sup. Fig. 1). Interestingly, the number of microparticles ( Fig. 2D) and their intensity per cell ( Fig. 2E) increased in the first three days, which may be due to cell death, phagocytosi...

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Non-Genetic Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype

Wofford

Singh

Cullen

et al. 2019

Preprint

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“…In another study, Nguyen et al. presented the electromagnetic actuation and chemotaxis of cellular microrobots carrying paclitaxel‐encapsulated magnetic liposomes in vitro in breast and colorectal cancer models …”

Section: Therapeutic Applications Of Microrobotsmentioning

confidence: 99%

Mobile Microrobots for Active Therapeutic Delivery

Erkoc

Yasa

Ceylan

et al. 2018

Advanced Therapeutics

199

170

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Recent advances in the versatility and sophistication of design, fabrication, and control methods of mobile microrobots could have a transforming impact on future healthcare technologies. Self-propelled or remotely actuated, synthetic, or biohybrid microrobots can navigate to difficult-to-reach regions in the human body to deliver therapeutics for microscopically localized medical interventions. Here, recent progress in the design of microrobotic systems concerning therapeutic delivery of drugs, cells, and genetic materials is reported. This perspective prioritizes the design aspects of microrobots for medical cargo loading, navigation in biologically relevant environments, and controlled cargo release. In the final section, future prospects and a discussion on the critical shortcomings for the benchside-to-bedside translation of medical microrobots are provided.

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“…Several types of NPs that exhibited good biocompatibility, biodegradability, and capability to load hydrophilic/hydrophobic drugs were widely studied for drug carrying. Liposomes (including unilamellar and multilamellar) enhanced the maximum tolerated dose (MTD) 20-fold in MAs of PTX [ 71 ] and 50–200-fold for Dox [ 30 , 67 ]. It was also reported that poly(lactic-co-glycolic acid) (PLGA) NPs were able to enhance 5-fold higher for Dox MTD for MAs [ 64 ], yet no obvious change was observed for PTX MTD on MSCs [ 69 ].…”

Section: Loading Strategies For Cargo Amounts and Cell Function Balancementioning

confidence: 99%

“…RGD is a short peptide that targets α v β 3 integrin-positive tumors, and modifying RBCs with RGD allowed an obvious attachment in tumors that native RBCs could not achieve [ 23 , 48 ] For magnetizing modification, cell carriers have internalized magnetic particles, such as Fe 3 O 4 , to follow guidance from electromagnetic fields. This method was widely studied as external assistance to control the cell path, and MA motion and speed were found to be enhanced 29 times that of normal cells [ 71 ]. Along with this, it may improve SMAP capability and make a concession to the premise of reducing early leakage risk …”

Section: Cascade Strategies For Improving Cell-driven Targeting Delivery Efficiencymentioning

confidence: 99%

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform

Gao

Zou

Zhao

et al. 2021

Stem Cells International

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Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

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Feasibility study of dual-targeting paclitaxel-loaded magnetic liposomes using electromagnetic actuation and macrophages

Cited by 38 publications

References 27 publications

Non-Genetic Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype

Non-Genetic Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype

Mobile Microrobots for Active Therapeutic Delivery

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform

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