Intravital microscopy for real-time monitoring of drug delivery and nanobiological processes

Momoh, Jeffrey; Kapsokalyvas, Dimitrios; Vogt, Michael; Hak, Sjoerd; Kießling, Fabian; Zandvoort, Marc van; Lammers, Twan; Sofias, Alexandros Marios

doi:10.1016/j.addr.2022.114528

Cited by 7 publications

(7 citation statements)

References 176 publications

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“…Overall, we did observe slightly higher CCPM accumulation in PANC-1 tu-mors as compared to 4T1 tumors as a result of passive targeting, that is, not induced by TME modulation by TMX. Given the comparable levels of blood vessel density and perfusion in both models, it seems plausible that the threefold higher amount of tumor-associated macrophages, which have been recognized as a nanoparticle reservoir in (or hitchhiker to) solid tumors, [57][58][59] may explain the higher accumulation of the polymeric drug delivery system in PANC-1 tumors.…”

Section: Discussionmentioning

confidence: 99%

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

Biancacci,

De Santis,

Rama

et al. 2023

Advanced Therapeutics

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The dense stromal matrix in fibrotic tumors hinders tumor‐targeted drug delivery. Tamoxifen (TMX), an estrogen receptor modulator that is clinically used for the treatment of breast cancer, is shown to reprogram the tumor microenvironment (TME) and to alleviate desmoplasia. It is investigated if TMX, administered in free and nano‐formulated form, can be repurposed as a TME remodeling agent to improve tumor accumulation of nano‐formulations in pancreatic ductal adenocarcinoma and triple‐negative breast cancer mouse models, evaluated using clinical‐stage Cy7‐labeled core‐crosslinked polymeric micelles (CCPM). Under control conditions, higher levels of Cy7‐CCPM are found in PANC‐1 tumors (16.7% ID g−1 at 48 h post i.v. injection) than in 4T1 tumors (11.0% ID g−1). In both models, free and nano‐formulated TMX failed to improve CCPM delivery. These findings are congruent with the results from histopathological immunofluorescence analysis of tumor tissue, which indicate that TMX treatment does not significantly change vascularization, perfusion, macrophage infiltration, collagen density, and collagen fiber thickness. Altogether, these results demonstrate that in PANC‐1 and 4T1 mouse models, TMX treatment does not contribute to beneficial TME priming and enhanced tumor‐targeted drug delivery.

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Section: Discussionmentioning

confidence: 99%

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

Biancacci,

De Santis,

Rama

et al. 2023

Advanced Therapeutics

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“…Intravital microscopy offers real-time analysis of NP transport into tumors, though owing to lower resolution. [221] There is considerable debate regarding whether NPs infiltrate the tumor microenvironment via paracellular or transcellular processes, yet arriving at a definitive answer remains challenging. This uncertainty stems from several factors.…”

Section: Methods To Investigate Transcytosismentioning

confidence: 99%

“…Intravital microscopy offers real‐time analysis of NP transport into tumors, though owing to lower resolution. [ 221 ]…”

Section: Enhanced Drug Delivery Strategy: Transcytosismentioning

confidence: 99%

Stimuli‐Responsive Nanocarriers for Transcytosis‐Based Cancer Drug Delivery

Wang,

Sun,

Shen

et al. 2024

Advanced NanoBiomed Research

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Significant challenges persist in enhancing the delivery efficiency of tumor nanomedicines, predominantly due to the difficulty of successfully surpassing pathophysiological barriers. Enhancing tumor penetration of nanomedicines in such conditions represents a pivotal goal in advancing anticancer nanotherapeutics. Transcytosis emerges as a promising solution in this context, addressing the limitations of passive drug delivery. By harnessing diverse stimuli to induce transcytosis, nanocarriers can achieve precise drug delivery and deep tumor penetration, resulting in high therapeutic efficacy and reduced systemic exposure to the therapeutic compound. This review briefly examines various stimuli‐responsive nanosystems and offers an overview and outlook on the development of stimuli‐responsive nanocarriers for transcytosis‐based cancer drug delivery, aiming to provide informative insights for the design of nanomedicines capable of deep tissue penetration and enhanced therapeutic efficacy.

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“…Therapeutic nanoparticle (TNP) drug delivery systems have been developed to extend drug pharmacokinetics, reduce toxicities, and target cancer cells more specifically by exploiting the enhanced permeability and retention (EPR) effect in tumors. [6] Despite clinical successes, [7,8] TNP faces challenges related to uneven tumor accumulation [9,10] and off-target uptake in organs like the liver. To address these issues, we must a) enhance drug penetration from TNP into tumors, and b) widen the TNP therapeutic window by maximizing drug payload in tumors over off-target tissues.…”

Section: Introductionmentioning

confidence: 99%

Sustained and Localized Drug Depot Release Using Radiation‐Activated Scintillating Nanoparticles

Kang,

Quintana,

et al. 2024

Advanced Materials

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Clinical treatment of cancer commonly incorporates X‐ray radiation therapy (XRT), and developing spatially‐precise radiation‐activatable drug delivery strategies may improve XRT efficacy while limiting off‐target toxicities associated with systemically administered drugs. Nevertheless, achieving this has been challenging thus far because strategies typically rely on radical species with short lifespans, and the inherent nature of hypoxic and acidic tumor microenvironments may encourage spatially heterogeneous effects. We hypothesized that the challenge could be bypassed by using scintillating nanoparticles that emit light upon X‐ray absorption, locally forming therapeutic drug depots in tumor tissues. We thus developed a nanoparticle platform ( Scintillating nanoparticle Drug Depot; SciDD) that enables the local release of cytotoxic payloads only after activation by XRT, thereby limiting off‐target toxicity. As a proof‐of‐principle, SciDD was used to deliver a microtubule‐destabilizing payload MMAE (monomethyl auristatin E). With as little as a 2 Gy local irradiation to tumors, MMAE payloads were released effectively to kill tumor cells. XRT‐mediated drug release was demonstrated in multiple mouse cancer models and showed efficacy over XRT alone (p < 0.0001). This work shows that SciDD can act as a local drug depot with spatiotemporally controlled release of cancer therapeutics.This article is protected by copyright. All rights reserved

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Intravital microscopy for real-time monitoring of drug delivery and nanobiological processes

Cited by 7 publications

References 176 publications

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

Stimuli‐Responsive Nanocarriers for Transcytosis‐Based Cancer Drug Delivery

Sustained and Localized Drug Depot Release Using Radiation‐Activated Scintillating Nanoparticles

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