Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer

Layek, Buddhadev; Shetty, Mihir; Nethi, Susheel Kumar; Sehgal, Drishti; Starr, Timothy K.; Prabha, Swayam

doi:10.3390/cancers12040965

Cited by 19 publications

(18 citation statements)

References 61 publications

(76 reference statements)

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“…Furthermore, exogenous microRNAs delivered by MSCs also assist in antitumor therapy, which deserves further clinical evaluation [492][493][494]. Another valid use of modified MSCs is to load various anti-tumor drugs, which has been extensively tested in numerous cancer types with significant inhibiting tumor growth and improving the anti-cancer efficacy of chemotherapeutic drugs [495][496][497].…”

Section: Mscs As Potential Therapeutic Targetmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

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Section: Mscs As Potential Therapeutic Targetmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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“…However, the maintenance dose of nano-MSCs is limited by the relatively large size of this therapeutic modality [ 60 ]. From our experimental experience, administrating an IV dose greater than 4 × 10 6 nano-MSCs may increase the chance of forming cell clots within blood vessels and cause immediate death of experimental animals [ 15 , 61 ]. Thus, a maximal maintenance dose of 2 × 10 6 MSCs (equivalent to 50 μg or 2.5 mg/kg PTX) was simulated.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic—Pharmacodynamic Modeling of Tumor Targeted Drug Delivery Using Nano-Engineered Mesenchymal Stem Cells

et al. 2021

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Nano-engineered mesenchymal stem cells (nano-MSCs) are promising targeted drug delivery platforms for treating solid tumors. MSCs engineered with paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are efficacious in treating lung and ovarian tumors in mouse models. The quantitative description of pharmacokinetics (PK) and pharmacodynamics (PD) of nano-MSCs is crucial for optimizing their therapeutic efficacy and clinical translatability. However, successful translation of nano-MSCs is challenging due to their complex composition and physiological mechanisms regulating their pharmacokinetic-pharmacodynamic relationship (PK–PD). Therefore, in this study, a mechanism-based preclinical PK–PD model was developed to characterize the PK–PD relationship of nano-MSCs in orthotopic A549 human lung tumors in SCID Beige mice. The developed model leveraged literature information on diffusivity and permeability of PTX and PLGA NPs, PTX release from PLGA NPs, exocytosis of NPs from MSCs as well as PK and PD profiles of nano-MSCs from previous in vitro and in vivo studies. The developed PK–PD model closely captured the reported tumor growth in animals receiving no treatment, PTX solution, PTX-PLGA NPs and nano-MSCs. Model simulations suggest that increasing the dosage of nano-MSCs and/or reducing the rate of PTX-PLGA NPs exocytosis from MSCs could result in improved anti-tumor efficacy in preclinical settings.

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“…After three times wash, the sections were incubated with 3,3'-diaminobenzidine (DAB) tetrahydrochloride and followed by a counterstain with hematoxylin 62 . The photographs of slides were taken by using a digital light microscope (Olympus, Japan), and the percentage of tumor cells that were positive for the Ki-67 as a proliferation biomarker was quantified using ImageJ software 63 .…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer

Golpich

Amini

Kefayat

et al. 2022

Sci Rep

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Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.

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Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer

Cited by 19 publications

References 61 publications

Targeting the tumor stroma for cancer therapy

Targeting the tumor stroma for cancer therapy

Pharmacokinetic—Pharmacodynamic Modeling of Tumor Targeted Drug Delivery Using Nano-Engineered Mesenchymal Stem Cells

In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer

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