Folate-Targeted Liposome Encapsulating Chitosan/Oligonucleotide Polyplexes for Tumor Targeting

Kang, Ji Hee; Battogtokh, Gantumur; Ko, Young Tag

doi:10.1208/s12249-014-0136-5

Cited by 23 publications

(8 citation statements)

References 27 publications

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“…In addition, the constructed resveratrol-containing liposomes exposed the molecules TPP or DQA on their surface to target specifically the mitochondria. In this study, the mitochondriotropic liposomes were constructed with rational lipid composition and thin-film hydration followed by the extrusion method according to previously published method [33,43], the amount of mitochondrial targeting ligand was decided as the amount to exert a targeting effect [2,44,45]. Table 1 shows the average particle sizes, polydispersity index (PDI) and zeta potentials of LS (Res), TLS (Res) and DLS (Res).…”

Section: Resultsmentioning

confidence: 99%

“…The TLS (Res) and DLS (Res) were prepared using a previously reported method with minor modifications [33]. The following lipids (total amount of 2 mg) were dissolved in chloroform: POPC:cholesterol:PEG-PE (7:3:0.15 in μmol) and 100 μg of resveratrol dissolved in ethanol was added to the lipid/chloroform solution.…”

Section: Methodsmentioning

confidence: 99%

“…The PEG-stabilized liposomes have been successfully applied for the in vivo delivery of various therapeutic agents, including nucleic acids, proteins and small molecules [2,33,34]. Liposomes consist of a phospholipid-formed bilayer and can be formulated in different sizes, ranging from a few to tens of micrometers [35,36].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Kang

2019

Pharmaceutics

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Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) and dequalinium-polyethylene glycol-distearoylphosphatidylethanolamine (DQA-DSPE-PEG) were synthesized as mitochondriotropic molecules. Mitochondria-targeting liposomes carrying resveratrol were constructed by modifying the liposome’s surface with TPP-PEG or DQA-PEG, resulting in TLS (Res) and DLS (Res), respectively, with the aim to obtain longer blood circulation and enhanced permeability and retention (EPR). Both TLS (Res) and DLS (Res) showed dimensions of approximately 120 nm and a slightly positive zeta potential. The enhanced cellular uptake and selective accumulation of TLS (Res) and DLS (Res) into the mitochondria were demonstrated by behavioral observation of rhodamine-labeled TLS or DLS, using confocal microscopy, and by resveratrol quantification in the intracellular organelle, using LC–MS/MS. Furthermore, TLS (Res) and DLS (Res) induced cytotoxicity of cancer cells by generating reactive oxygen species (ROS) and by dissipating the mitochondrial membrane potential. Our results demonstrated that TLS (Res) and DLS (Res) could provide a potential strategy to treat cancers by mitochondrial targeting delivery of therapeutics and stimulation of the mitochondrial signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Kang

2019

Pharmaceutics

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“…The Pha@FPPC (FPPC polymer micelles encapsulating Pha) emerged as favorable sphere morphology under the TEM (~93.0 nm) with good dispersion and stability in PBS (pH 7.4) and could be well released in vitro at pH value of 5.2. After tumor cellular untaken by FA-receptor-mediated endocytosis,18–20 PAsp segments became hydrophilic, responding to the acidic pH of endosomes or lysosome, and Pha was rapidly released from unlocked FPPC into the cytoplasm. Therefore, the drug-delivery carrier FPPC could effectively increase the therapeutical concentration of hydrophobic photosensitizer Pha in the tumor site and decrease the systemic cytotoxicity of Pha and chidamide.…”

Section: Resultsmentioning

confidence: 99%

<p>Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy</p>

Ma¹,

Hu²,

Guo³

et al. 2019

IJN

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Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol- b -poly(aspartic acid) (PEG- b -PAsp) grafted folate (FA-PEG- b -PAsp) to obtain the block polymer folate polyethylene glycol- b -poly(asparaginyl-chidamide) (FA-PEG- b -PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide- a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol- b -poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.

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“…It seems that mitochondrial-targeted NPs have great therapeutic impacts [247][248][249]. Liposomes are one of the most important nanocarriers that can be applied in the delivery of small molecules and genes [250,251]. Liposomes have a number of great properties such as high biocompatibility and capability of encapsulating both hydrophilic and hydrophobic drugs [252,253].…”

Section: Selective Targeting Of Mitochondria In Cancer Therapy Using mentioning

confidence: 99%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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Folate-Targeted Liposome Encapsulating Chitosan/Oligonucleotide Polyplexes for Tumor Targeting

Cited by 23 publications

References 27 publications

Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

<p>Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy</p>

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

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