Computational Nanomedicine: Modeling of Nanoparticle-Mediated Hyperthermal Cancer Therapy

Kaddi, Chanchala; Phan, John H.; Wang, May D.

doi:10.2217/nnm.13.117

Cited by 56 publications

(31 citation statements)

References 74 publications

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“…Nanotherapeutic response can be simulated by describing tumors as physical objects subject to physical laws, such as conservation of mass and momentum. Extensive modeling work studying tumor growth as well as angiogenesis has been published in recent years, as reviewed in [119–137] and associated references, with a subset of studies focusing on nanotherapy [24,27,138–148]. For example, the interaction between NP vascular extravasation, uptake, and distribution with heterogeneous tumor interstitial, vascular, and lymphatic conditions was studied in [140], finding that an elevated interstitial hydraulic conductivity leads to low NP accumulation regardless of NP capacity for vascular extravasation.…”

Section: Evaluation Of Nanotherapy Using Computational Modelingmentioning

confidence: 99%

Evaluation of uptake and distribution of gold nanoparticles in solid tumors

2015

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Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticuloendothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

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Section: Evaluation Of Nanotherapy Using Computational Modelingmentioning

confidence: 99%

Evaluation of uptake and distribution of gold nanoparticles in solid tumors

2015

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“…With regards to MNPs, however, almost all MNPs in the past MNHT treatments were injected directly into the tumor tissue. Attempts have been made recently to attach tumor- [88] and Rodrigues et al [89].…”

Section: Future Perspectivementioning

confidence: 99%

Antitumor Immunity by Magnetic Nanoparticle-Mediated Hyperthermia

et al. 2014

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Magnetic nanoparticle-mediated hyperthermia (MNHT) generates heat to a local tumor tissue of above 43°C without damaging surrounding normal tissues. By applying MNHT, a significant amount of heat-shock proteins is expressed within and around the tumor tissues, inducing tumor-specific immune responses. In vivo experiments have indicated that MNHT can induce the regression of not only a local tumor tissue exposed to heat, but also distant metastatic tumors unexposed to heat. In this article, we introduce recent progress in the application of MNHT for antitumor treatments and summarize the mechanisms and processes of its biological effects during antitumor induction by MNHT. Several clinical trials have been conducted indicating that the MNHT system may add a promising and novel approach to antitumor therapy.

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“…However, in vitro models lack key features of cancerous tissue found in vivo, including a vascular network, while in vivo models present challenges due to systemic interactions that may be difficult to tease apart. As a complement to these experimental approaches, computational simulation of cancer nanotherapy has aimed to provide the capability for system-level analysis 9, 16, 18, 19, 24, 27–30, 43, 44, 46 . In particular, we have recently studied via mathematical modeling the extravasation, uptake, and distribution of nanoparticles subject to heterogeneous tumor tissue and vascular conditions 5, 6, 40 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Drug-Loaded Gold Nanoparticle Cytotoxicity as a Function of Tumor Vasculature-Induced Tissue Heterogeneity

Miller

Frieboes

2018

Ann Biomed Eng

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The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-mediated drug delivery. This heterogeneity spans from the molecular (genomic, proteomic, metabolomic) to the cellular (cell types, adhesion, migration) and to the tissue (vasculature, extra-cellular matrix) scales. In particular, tumor vasculature forms abnormally, inducing proliferative, hypoxic, and necrotic tumor tissue regions. As the vasculature is the main conduit for nanotherapy transport into tumors, vasculature-induced tissue heterogeneity can cause local inadequate delivery and concentration, leading to subpar response. Further, hypoxic tissue, although viable, would be immune to the effects of cell-cycle specific drugs. In order to enable a more systematic evaluation of such effects, here we employ computational modeling to study the therapeutic response as a function of vasculature-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated interacting with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results quantify the influence that varying levels of tumor vascular density coupled with the drug strength have on nanoparticle uptake and washout, and the associated tissue response. The drug strength affects the proportion of proliferating, hypoxic, and necrotic tissue fractions, which in turn dynamically affect and are affected by the vascular density. Higher drug strengths may be able to achieve stronger tumor regression but only if the intra-tumoral vascular density is above a certain threshold that affords sufficient transport. This study establishes an initial step towards a more systematic methodology to assess the effect of vasculature-induced tumor tissue heterogeneity on the response to nanotherapy.

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Computational Nanomedicine: Modeling of Nanoparticle-Mediated Hyperthermal Cancer Therapy

Cited by 56 publications

References 74 publications

Evaluation of uptake and distribution of gold nanoparticles in solid tumors

Evaluation of uptake and distribution of gold nanoparticles in solid tumors

Antitumor Immunity by Magnetic Nanoparticle-Mediated Hyperthermia

Evaluation of Drug-Loaded Gold Nanoparticle Cytotoxicity as a Function of Tumor Vasculature-Induced Tissue Heterogeneity

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