Anticancer Platelet‐Mimicking Nanovehicles

Hu, Quanyin; Sun, Wujin; Qian, Chengen; Wang, Chao; Bomba, Hunter N.; Gu, Zhen

doi:10.1002/adma.201503323

Cited by 547 publications

(467 citation statements)

References 50 publications

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“…This membraneencapsulated strategy allows for greater circulation time, since high clearance rates are often a hindrance to effectively targeted drug delivery, decreased immunogenicity, and improved specific targeting. 59 Cloaked drug delivery can also suppress the complement system, increasing the Figure 5 (a) Schematic of platelet membrane-enclosed nanovehicle drug delivery mechanism developed by Hu et al 59 Platelet membranes are isolated via centrifugation and then used to enclose the doxorubicin-nanovehicle particle. The membrane-doxorubicin-nanovehicle particle is loaded with TNF-related apoptosis ligand (TRAIL) and inserted into the bloodstream, where it can target and deliver doxorubicin and TRAIL to circulating tumor cells.…”

Section: Cloaking and Active Targeting Mechanisms For Drug Deliverymentioning

confidence: 99%

“…antimicrobial efficacy of the system, and has several potential applications in the field of cancer nanomedicine due to the natural aggregation of platelets around metastatic tumors. 32,59,60 The Gu research group has developed a platform for delivering anticancer drugs within a platelet membraneenclosed nanovehicle ( Figure 5(a)). The outer platelet membrane shell of the particle is coated with proteins such as P-selectin, which allow the particle to bind CD44 receptors on cancer cells, and the inner nanogel is loaded with doxorubicin, a small-molecule anticancer drug that can be released upon internalization and subsequent digestion of the particle by cancer cells.…”

Section: Cloaking and Active Targeting Mechanisms For Drug Deliverymentioning

confidence: 99%

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Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Nandi

Brown

2016

Exp Biol Med (Maywood)

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Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic plateletmimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics.

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Section: Cloaking and Active Targeting Mechanisms For Drug Deliverymentioning

confidence: 99%

Section: Cloaking and Active Targeting Mechanisms For Drug Deliverymentioning

confidence: 99%

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Nandi

Brown

2016

Exp Biol Med (Maywood)

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“…To investigate the endocytosis pathway, the cells were cultured at different temperatures (37 °C, 25 °C, and 4 °C) in the presence of DOX (1 μM) or the VPA and DOX combination (DOX concentration, 1 μM) for 3 h. It has been established that the incubation of cells at 4 °C could block endocytosis [28]. Concurrently, cells were pre-treated for 1 h with various kinds of specific endocytosis inhibitors: CPZ (10 μM), an inhibitor of clathrin-mediated endocytosis [51]; MβCD (3 mM), an inhibitor of caveolae-mediated endocytosis [51]; and LY (20 μM), an inhibitor of macropinocytosis [46]. After incubation for 3 h with DOX or the VPA and DOX combination, the cells were washed twice with PBS and the fluorescent intensity of DOX in the cells was evaluated using the fluorescence microplate reader (GeminiEM) with excitation and emission wavelengths of approximately 470 nm and 570 nm, respectively.…”

Section: Determination Of the Endocytosis Pathwaysmentioning

confidence: 99%

“…For the quantitative analysis of the internalized DOX, cells were lysed with a protein lysis buffer and fluorescence was measured using the fluorescence microplate reader (GeminiEM) with excitation and emission wavelengths of approximately 470 nm and 570 nm, respectively. To normalize the intracellular DOX concentrations, the DOX concentration was divided by the protein concentration, as previously described [51].…”

Section: Dox Internalization Analysismentioning

confidence: 99%

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Anti-Proliferation Effects in Hepatocellular Carcinoma Cells

Saha¹,

Yin²,

Kim³

et al. 2017

Preprint

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Abstract:We evaluated the mono-and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

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“…It was found that nanoparticle loading in cells did not affect its migration, chemotaxic ability. In addition, exosomes, cell membrane components, microvesicles, which originated from cells, can mimic the function of cells to deliver drug into targeted tissue in noninvasive way (Haney et al, 2015;Hu et al, 2015;Peng et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

et al. 2017

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Cell-mediated drug delivery systems employ specific cells as drug vehicles to deliver drugs to targeted sites. Therapeutics or imaging agents are loaded into these cells and then released in diseased sites. These specific cells mainly include red blood cells, leukocytes, stem cells and so on. The cell acts as a Trojan horse to transfer the drug from circulating blood to the diseased tissue. In such a system, these cells keep their original properties, which allow them to mimic the migration behavior of specific cells to carry drug to the targeted site after in vivo administration. This strategy elegantly combines the advantages of both carriers, i.e. the adjustability of nanoparticles (NPs) and the natural functions of active cells, which therefore provides a new perspective to challenge current obstacles in drug delivery. This review will describe a fundamental understanding of these cell-based drug delivery systems, and discuss the great potential of combinational application of cell carrier and NPs.

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Anticancer Platelet‐Mimicking Nanovehicles

Cited by 547 publications

References 50 publications

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Anti-Proliferation Effects in Hepatocellular Carcinoma Cells

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

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