Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems &lt;I&gt;In Vitro&lt;/I&gt;

Privalova, A. M.; Uglanova, S. V.; Кузнецова, Н. В.; Klyachko, Natalia L.; Golovin, Yuri I.; Коренков, В. В.; Водовозова, Е. Л.; Марквичева, Елена

doi:10.1166/jnn.2015.10508

Cited by 14 publications

(11 citation statements)

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“…This requires conducting studies using three-dimensional models that approximate the cellular and molecular composition of tumours. Researchers grow multicellular tumour spheroids , or MTS [178], seed porous scaffolds [179], and create miniature versions of various organs connected by vascular canals called ‘Chips’ [180]. Such models will help researchers develop therapies that act on tissues and systems and not just at the cellular and molecular levels.…”

Section: Metastasis In Target Organsmentioning

confidence: 99%

Cancer and the metastatic substrate

Arvelo¹,

Sojo²,

Cotte³

2016

ecancer

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Seventy percent of cancer patients have detectable metastases when they receive a diagnosis and 90% of cancer deaths result from metastases. These two facts emphasise the urgency for research to study the mechanisms and processes that enable metastasis. We need to develop a greater understanding of the cellular and molecular mechanisms that cause metastasis and also we need to do more. We must also consider the micro- and macro-environmental factors that influence this disease. Studying this environmental context has led us to update the ‘seed and soil’ hypothesis which dates back to the 19th century. This theory describes cancerous cells as seeds and the substrate as the soil in target organs though this may seem antiquated. Nonetheless, the tissue specificity that researchers have recently observed in metastatic colonisation supports the validity of the seed and soil theory. We now know that the metastatic potential of a tumour cell depends on multiple, reciprocal interactions between the primary tumour and distant sites. These interactions determine tumour progression. Studies of metastasis have allowed us to develop treatments that focus on therapeutic effectiveness. These new treatments account for the frequent metastasis of some tumours to target organs such as bones, lungs, brain, and liver. The purpose of this review is first to describe interactions between the cellular and molecular entities and the target organ tumour environment that enables metastasis. A second aim is to describe the complex mechanisms that mediate these interactions.

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Section: Metastasis In Target Organsmentioning

confidence: 99%

Cancer and the metastatic substrate

Arvelo¹,

Sojo²,

Cotte³

2016

ecancer

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“…They can also be used to generate organized cell arrangements in vitro according to the disease or tissue being studied, which is an advantage over 2D and several scaffold-free cell models [15]. Several natural (alginate [16], collagen [17], hyaluronic acid [18], basement membrane matrix [19]) and synthetic (poly(lactic acid-co-glycolic acid) [3], polycaprolactone [18], polyethylene glycol [20], polylactic acid [21]) polymer-based particles have been utilized to develop in vitro cancer models for various cancer studies.…”

Section: Introductionmentioning

confidence: 99%

Scaffold-based lung tumor culture on porous PLGA microparticle substrates

Kuriakose

Nguyen

et al. 2019

PLoS ONE

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Scaffold-based cancer cell culture techniques have been gaining prominence especially in the last two decades. These techniques can potentially overcome some of the limitations of current three-dimensional cell culture methods, such as uneven cell distribution, inadequate nutrient diffusion, and uncontrollable size of cell aggregates. Porous scaffolds can provide a convenient support for cell attachment, proliferation and migration, and also allows diffusion of oxygen, nutrients and waste. In this paper, a comparative study was done on porous poly (lactic-co-glycolic acid) (PLGA) microparticles prepared using three porogens—gelatin, sodium bicarbonate (SBC) or novel poly N-isopropylacrylamide [PNIPAAm] particles, as substrates for lung cancer cell culture. These fibronectin-coated, stable particles (19–42 μm) supported A549 cell attachment at an optimal cell seeding density of 250,000 cells/ mg of particles. PLGA-SBC porous particles had comparatively larger, more interconnected pores, and favored greater cell proliferation up to 9 days than their counterparts. This indicates that pore diameters and interconnectivity have direct implications on scaffold-based cell culture compared to substrates with minimally interconnected pores (PLGA-gelatin) or pores of uniform sizes (PLGA-PMPs). Therefore, PLGA-SBC-based tumor models were chosen for preliminary drug screening studies. The greater drug resistance observed in the lung cancer cells grown on porous particles compared to conventional cell monolayers agrees with previous literature, and indicates that the PLGA-SBC porous microparticle substrates are promising for in vitro tumor or tissue development.

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“…Recently, we have demonstrated that cells in microencapsulated spheroids were more resistant than those in monolayer culture against both free drugs 25 and nano-sized drug delivery systems, namely docetaxel-loaded nanoemulsions or methotrexate prodrug liposomal formulations. 26 In the current study, RI of the cells in the microencapsulated tumor spheroids against native DOX was found to be approx. 20-fold higher compared to that in the monolayer cell culture.…”

Section: Discussionmentioning

confidence: 56%

Novel Doxorubicin Derivatives: Synthesis and Cytotoxicity Study in 2D and 3D in Vitro Models

Akasov¹,

Drozdova²,

Zaytseva-Zotova³

et al. 2017

Adv Pharm Bull

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Purpose: Multidrug resistance (MDR) of tumors to chemotherapeutics often leads to failure of cancer treatment. The aim of the study was to prepare novel MDR-overcoming chemotherapeutics based on doxorubicin (DOX) derivatives and to evaluate their efficacy in 2D and 3D in vitro models.Methods: To overcome MDR, we synthesized five DOX derivatives, and then obtained non-covalent complexes with human serum albumin (HSA). Drug efficacy was evaluated for two tumor cell lines, namely human breast adenocarcinoma MCF-7 cells and DOX resistant MCF-7/ADR cells. Additionally, MCF-7 cells were entrapped in alginate-oligochitosan microcapsules, and generated tumor spheroids were used as a 3D in vitro model to study cytotoxicity of the DOX derivatives.Results: Due to 3D structure, the tumor spheroids were more resistant to chemotherapy compared to monolayer culture. DOX covalently attached to palmitic acid through hydrazone linkage (DOX-N2H-Palm conjugate) was found to be the most promising derivative. Its accumulation levels within MCF-7/ADR cells was 4- and 10-fold higher than those of native DOX when the conjugate was added to cultivation medium without serum and to medium supplemented with 10% fetal bovine serum, respectively. Non-covalent complex of the conjugate with HSA was found to reduce the IC50 value from 32.9 µM (for free DOX-N2H-Palm) to 16.8 µM (for HSA-DOX-N2H-Palm) after 72 h incubation with MCF-7/ADR cells.Conclusion: Palm-N2H-DOX conjugate was found to be the most promising DOX derivative in this research. The formation of non-covalent complex of Palm-N2H-DOX conjugate with HSA allowed improving its anti-proliferative activity against both MCF-7 and MCF-7/ADR cells.

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Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems <I>In Vitro</I>

Cited by 14 publications

References 0 publications

Cancer and the metastatic substrate

Cancer and the metastatic substrate

Scaffold-based lung tumor culture on porous PLGA microparticle substrates

Novel Doxorubicin Derivatives: Synthesis and Cytotoxicity Study in 2D and 3D in Vitro Models

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