Nanoparticle Activation Methods in Cancer Treatment

White, B. D.; Duan, Chengchen; Townley, Helen E.

doi:10.3390/biom9050202

Cited by 29 publications

(29 citation statements)

References 128 publications

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“…On top of passive accumulation, tumor eradication could be improved by active targeting. In the past, nanoparticles have been designed with pH-responsive activity, making use of the altered pH-environment within cells with enhanced metabolism, especially cancer cells [65,66]. Since many tumors have also shown altered enzyme expression, similar effects can be achieved by nanoparticles that are enzyme-triggered and activated specifically at the tumor site [67,68].…”

Section: Discussionmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation

et al. 2020

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Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired as well. This limits the administered dose and eventually allows tumor cells to escape treatment. In order to increase intratumoral drug concentration and simultaneously reduce systemic side effects, nanoparticles have come into focus as drug carriers. The functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with chemotherapeutics such as mitoxantrone (MTO) enables targeted drug transport by using magnetic forces. Here, we investigate SPIONs consisting of individual iron oxide cores of 10 nm in diameter and a total hydrodynamic diameter of 53 ± 0.8 nm as a transporting system for MTO. Comparing the killing efficacy in monolayer cell culture and multicellular tumor spheroids of HT-29 cells, we show that spheroids tolerate considerably higher doses of nanoparticle-loaded MTO. Therefore, dose predictions from conventional monolayer cell cultures are often misleading for in vivo applications. This was true for both soluble and nanoparticle-bound MTO. Using flow chambers mimicking in vivo blood flow, we furthermore demonstrate that SPIONs can magnetically accumulate MTO. We conclude that SPIONs can function as an effective delivery platform to increase local drug concentrations, thereby potentially overcoming chemotherapy resistance of cells.

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Section: Discussionmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation

et al. 2020

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“…These are diverse molecular structures, including lipid micelles, liposome composites of phospholipid and other molecules, and polymer-based particles, with the common property that they form a vesicle that can be loaded with therapeutic agents and which can then cross the BBB to enter the parenchyma ( 226 ). Once within the brain, variation in environmental pH at the tumor site, amongst other conditions destabilize the nanocarrier structure and trigger release of the cargo within the tissue ( 227 ). Although effective, these nanocarriers are indiscriminate and passively deliver their cargo widely across the brain, a drawback that has spurred the development of more effectively targeted nanocarrier delivery systems.…”

Section: Overcoming Gbm-driven Immunosuppressionmentioning

confidence: 99%

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

et al. 2020

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Glioblastoma multiforme (GBM) is the most frequently occurring primary brain tumor and has a very poor prognosis, with only around 5% of patients surviving for a period of 5 years or more after diagnosis. Despite aggressive multimodal therapy, consisting mostly of a combination of surgery, radiotherapy, and temozolomide chemotherapy, tumors nearly always recur close to the site of resection. For the past 15 years, very little progress has been made with regards to improving patient survival. Although immunotherapy represents an attractive therapy modality due to the promising pre-clinical results observed, many of these potential immunotherapeutic approaches fail during clinical trials, and to date no immunotherapeutic treatments for GBM have been approved. As for many other difficult to treat cancers, GBM combines a lack of immunogenicity with few mutations and a highly immunosuppressive tumor microenvironment (TME). Unfortunately, both tumor and immune cells have been shown to contribute towards this immunosuppressive phenotype. In addition, current therapeutics also exacerbate this immunosuppression which might explain the failure of immunotherapy-based clinical trials in the GBM setting. Understanding how these mechanisms interact with one another, as well as how one can increase the anti-tumor immune response by addressing local immunosuppression will lead to better clinical results for immune-based therapeutics. Improving therapeutic delivery across the blood brain barrier also presents a challenge for immunotherapy and future therapies will need to consider this. This review highlights the immunosuppressive mechanisms employed by GBM cancers and examines potential immunotherapeutic treatments that can overcome these significant immunosuppressive hurdles.

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“…This characteristic is globally recognized as an advantageous opportunity to promote passive tumor accumulation of nanoparticles and to facilitate their cellular uptake, depending on the nanoparticles physicochemical properties [148,149]. Moreover, compared to healthy tissues, tumor microenvironment has unique physicochemical features, including hypoxia, slightly acidic pH, active efflux pumps, hyperthermia and overexpression of several molecular biomarkers [150,151,152]. Considering this, a locally triggered drug release from nanosystems may be promoted by taking advantage of these intrinsic tumor biological peculiar conditions (e.g., pH, temperature and enzymes) or through the application of external stimuli (e.g., light, electric fields, magnetic fields or ultrasound) [144,152,153,154,155,156,157].…”

Section: Nanotechnology and Cancer Treatment—tackling Melanomamentioning

confidence: 99%

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosinase. In addition, the role of nanotechnology as a valuable strategy to effectively deliver selective drugs is emphasized, either incorporating/encapsulating synthetic molecules or natural-derived compounds in lipid-based nanosystems such as liposomes. Nanoformulated compounds have been explored for their improved anticancer activity against melanoma and promising results have been obtained. Indeed, they displayed improved physicochemical properties and higher accumulation in tumoral tissues, which potentiated the efficacy of the compounds in pre-clinical experiments. Overall, these experiments opened new doors for the discovery and development of more effective drug formulations for melanoma treatment.

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Nanoparticle Activation Methods in Cancer Treatment

Cited by 29 publications

References 128 publications

Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation

Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

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