Size‐Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature‐Based Differential Targeting in Triple Negative Breast Cancer

Goel, Shreya; Ferreira, Carolina A.; Dogra, Prashant; Yu, Bo; Kutyreff, Christopher J.; Siamof, Cerise M.; Engle, Jonathan W.; Barnhart, Todd E.; Cristini, Vittorio; Wang, Zhihui; Cai, Weibo

doi:10.1002/smll.201903747

Cited by 39 publications

(42 citation statements)

References 34 publications

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“…We recently demonstrated the application of image‐guided mathematical modeling to investigate the in vivo disposition of ultrasmall porous silica NPs in two mouse models of breast cancer (Figure ) (Goel et al, ). This was accomplished with a reduced PBPK model comprised of systemic circulation, liver, spleen, muscle, and tumor compartments.…”

Section: Image‐guided Mathematical Modelingmentioning

confidence: 99%

Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Dogra

Butner

Nizzero

et al. 2020

WIREs Nanomed Nanobiotechnol

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While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size‐dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non‐invasive in vivo imaging modalities. This allows for visualization and quantification of the whole‐body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non‐invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state‐of‐the‐art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Section: Image‐guided Mathematical Modelingmentioning

confidence: 99%

Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Dogra

Butner

Nizzero

et al. 2020

WIREs Nanomed Nanobiotechnol

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“…To perform 89 Zr radiolabeling of pDox NPs, pDox was first conjugated to p-SCN-Bn-Deferoxamine (DFO; Macrocyclics, Dallas, TX) via amine-isothiocyanate conjugation chemistry as described above (26). Final conjugates were obtained after filtration through PD-10 desalting columns (GE Healthcare, USA).…”

Section: Surface Modification Of Inpg-pdoxmentioning

confidence: 99%

Sequential deconstruction of composite drug transport in metastatic breast cancer

et al. 2020

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It is challenging to design effective drug delivery systems (DDS) that target metastatic breast cancers (MBC) because of lack of competent imaging and image analysis protocols that suitably capture the interactions between DDS and metastatic lesions. Here, we integrate high temporal resolution of in vivo whole-body PET-CT, ex vivo whole-organ optical imaging, high spatial resolution of confocal microscopy, and mathematical modeling, to systematically deconstruct the trafficking of injectable nanoparticle generators encapsulated with polymeric doxorubicin (iNPG-pDox) in pulmonary MBC. iNPG-pDox accumulated substantially in metastatic lungs, compared to healthy lungs. Intratumoral distribution and retention of iNPG-pDox varied with lesion size, possibly induced by locally remodeled microenvironment. We further used multiscale imaging and mathematical simulations to provide improved drug delivery strategies for MBC. Our work presents a multidisciplinary translational toolbox to evaluate transport and interactions of DDS within metastases. This knowledge can be recursively applied to rationally design advanced therapies for metastatic cancers.

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“…5 A, DIR@PVHs NP exhibited better accumulation in tumors than DIR@PVs micelles because HA actively targets CD44, which is overexpressed on tumor cells. However, the nanoparticles showed significant liver accumulation due to non-specific uptake by the reticuloendothelial system (RES) 51 and high expression of CD44 in liver cells. Treatment with DIR@PVHPs NP and DIR@PVHRs NP showed greater tumor accumulation at 24 and 48 h due to the ability of PEG to increase circulation time.…”

Section: Resultsmentioning

confidence: 99%

A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

Hou

Shou

et al. 2020

Acta Pharmaceutica Sinica B

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A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light, and have great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system (NDDS) to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A (DTA) fragment-encoded plasmids to tumor sites. The expression of DTA was induced by exposure to blue light. Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond, and PEGylated hyaluronic acid modified with RGD peptide, accumulated in tumor tissues and were actively internalized into 4T1 cells via dual targeting to CD44 and α v β 3 receptors. The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure. In vitro studies showed that light-induced DTA expression reduced 4T1 cell viability and induced apoptosis. Furthermore, the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4T1 tumor xenograft model, which resulted in excellent antitumor effects, reduced tumor angiogenesis, and no systemic toxicity. The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.

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Size‐Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature‐Based Differential Targeting in Triple Negative Breast Cancer

Cited by 39 publications

References 34 publications

Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Sequential deconstruction of composite drug transport in metastatic breast cancer

A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

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