Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Kumar, Dulla Naveen; Chaudhuri, Aiswarya; Deepa, D; Shekher, Anusmita; Gupta, Subash C.; Majumdar, Shreyasi; Krishnamurthy, S.; Singh, Sanjay; Kumar, Dinesh; Agrawal, Ashish Kumar

doi:10.3390/life12081143

Cited by 43 publications

(35 citation statements)

References 63 publications

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“…For evaluation of their cellular uptake, the isolated exosomes were fluorescently labeled using coumarin-6 as a lipophilic florescent dye (Liang et al., 2021 ; Kumar et al., 2022 ). In brief, equal volumes of exosomal dispersion in PBS and ethanolic dye solution (250 µg/mL) were incubated at 37 °C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis

et al. 2022

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Liver fibrosis is a global life-threatening disorder with no approved treatment. It leads to serious hepatic complications when progressive, such as cirrhosis and carcinoma. Luteolin (LUT) is a plant flavonoid possessing a promising therapeutic potential in various liver diseases particularly, liver fibrosis. It was reported to have potent anti-inflammatory and antioxidant properties. It also suppresses the proliferation of activated hepatic stellate cells (HSC) and induces their apoptosis. However, its poor aqueous solubility and exposure to metabolism hinder its clinical use. Mesenchymal stem cells (MSCs)-derived exosomes, nano-sized extracellular vesicles, have recently emerged as natural biocompatible drug delivery vehicles permitting efficient drug delivery. Accordingly, the present study aimed for the first time to investigate the potential of bone marrow MSCs-derived exosomes to improve LUTs antifibrotic effectiveness. LUT-loaded exosomes (LUT-Ex) were successfully developed, optimized and subjected to both in vitro and in vivo characterization. The elaborated LUT-Ex presented good colloidal properties (size; 150 nm, PDI; 0.3 and ζ-potential; −28 mV), typical vesicular shape, reasonable drug entrapment efficiency (40%) with sustained drug release over 72 h. Additionally, the cellular uptake study of coumarin-6-loaded exosomes in HEP-G2 revealed a significant enhancement in their uptake by 78.4% versus free coumarin-6 solution ( p ≤ 0.001). Following a single intraperitoneal injection, LUT-Ex revealed a superior antifibrotic activity compared with either LUT-suspension or blank exosomes as evidenced by the results of biochemical and histopathological evaluation. In conclusion, the elaborated LUT-Ex could be addressed as a promising nanocarrier for effective treatment of liver fibrosis.

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Section: Methodsmentioning

confidence: 99%

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis

et al. 2022

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“…They are basically generated by two invaginations of the plasma membrane. Exosomes are comprised of various surface proteins that are specific to the endosomal pathway, and can enclose nucleic acid, receptors, cytosolic proteins, and drugs [ 96 , 97 ]. The lipidic layer of exosomes varies from other types of extracellular vesicles such as apoptotic bodies and microvesicles as they are enriched in cholesterol and diacylglycerol [ 45 , 98 ].…”

Section: Lipid-based Nanoparticles: a Versatile Drug Delivery Systemmentioning

confidence: 99%

“…It was observed that developed exosomes showed an average particle size of 80–100 nm, with 82% entrapment efficiency. Moreover, the surface functionalized loaded exosomes showed increased cellular uptake and higher apoptotic index, compared to free drugs [ 97 ].…”

Section: Lipid-based Nanoparticles: a Versatile Drug Delivery Systemmentioning

confidence: 99%

Lipid-Based Nanoparticles as a Pivotal Delivery Approach in Triple Negative Breast Cancer (TNBC) Therapy

Chaudhuri

Kumar

Shaik

et al. 2022

IJMS

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Triple-negative breast cancer is considered the most aggressive type of breast cancer among women and the lack of expressed receptors has made treatment options substantially limited. Recently, various types of nanoparticles have emerged as a therapeutic option against TNBC, to elevate the therapeutic efficacy of the existing chemotherapeutics. Among the various nanoparticles, lipid-based nanoparticles (LNPs) viz. liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid nanocarriers, and lipid–polymer hybrid nanoparticles are developed for cancer treatment which is well confirmed and documented. LNPs include various therapeutic advantages as compared to conventional therapy and other nanoparticles, including increased loading capacity, enhanced temporal and thermal stability, decreased therapeutic dose and associated toxicity, and limited drug resistance. In addition to these, LNPs overcome physiological barriers which provide increased accumulation of therapeutics at the target site. Extensive efforts by the scientific community could make some of the liposomal formulations the clinical reality; however, the relatively high cost, problems in scaling up the formulations, and delivery in a more targetable fashion are some of the major issues that need to be addressed. In the present review, we have compiled the state of the art about different types of LNPs with the latest advances reported for the treatment of TNBC in recent years, along with their clinical status and toxicity in detail.

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“…Biomimetic tumor-derived exosomes loaded with (TEX)-Liposome-paclitaxel (PTX) Microtubule [228] Folic acid (FA)-functionalized bovine milk-derived ssEVs loaded with Paclitaxel (PAC) and 5-fluorouracil (5-FU) Microtubule/synthesis of DNA [229] miR-567 Cancer-associated ATG5 [230] let-7a miRNA EGFR [231] Ultrasonic sensitizer indocyanine green (ICG) Folic acid [232] Deintegrin and metalloproteinase 15 (A15), doxorubicin (Dox) and cholesterol-modified miRNA 159 DNA/GAMYB [233] Cationic bovine serum albumin (CBSA) conjugated siS100A4 nanoparticles Lung PMN [234] Surface display monoclonal antibodies against human CD3 and human HER2 Human CD3 and human HER2 [235] The conjugates of reactive oxygen species (ROS)-responsive sulfide-linked paclitaxel-Linoleic acid conjugates (PTXS-LA) and cucurbitin B (CuB) (EMPC) loaded with CD44…”

Section: Cell Cycle Quiescence and Chemotherapy-resistant Mesenchymal...mentioning

confidence: 99%

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance

Feng

Guo

Tanaka

et al. 2022

IJMS

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Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication. sEVs can transport a variety of bioactive substances, including proteins, RNAs, and lipids. Accumulating evidence has revealed that sEVs play a crucial role in cancer development and progression, with a significant impact on proliferation, invasion, and metastasis. In addition, sEVs systematically coordinate physiological and pathological processes, such as coagulation, vascular leakage, and stromal cell reprogramming, to bring about premetastatic niche formation and to determine metastatic organ tropism. There are a variety of oncogenic factors in tumor-derived sEVs that mediate cellular communication between local stromal cells and distal microenvironment, both of which are important in cancer progression and metastasis. Tumor-derived sEVs contain substances that are similar to parental tumor cells, and as such, sEVs could be biomarkers in cancer progression and potential therapeutic targets, particularly for predicting and preventing future metastatic development. Here, we review the mechanisms underlying the regulation by tumor-derived sEVs on cancer development and progression, including proliferation, metastasis, drug resistance, and immunosuppression, which coordinately shape the pro-metastatic microenvironment. In addition, we describe the application of sEVs to the development of cancer biomarkers and potential therapeutic modalities and discuss how they can be engineered and translated into clinical practice.

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Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Cited by 43 publications

References 63 publications

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis

Lipid-Based Nanoparticles as a Pivotal Delivery Approach in Triple Negative Breast Cancer (TNBC) Therapy

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance

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