Reducing off-target drug accumulation by exploiting a type-III interferon response

Tilden, Scott; Ricco, Madison; Hemann, Emily A.; Anchordoquy, Thomas J.

doi:10.1016/j.jconrel.2023.05.029

Cited by 3 publications

(1 citation statement)

References 77 publications

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“…Specifically, lipoplex administration promotes the release of IFN-λ, which reduces normal tissue permeability and off-target deposition of subsequently administered nanoparticles in organs and tissues, leading to increased uptake by tumors. 84 This study suggests that a better understanding of the interplay between nanoparticles and immune systems can greatly benefit nanodrug delivery systems' distribution, biocompatibility, safety, and efficacy.…”

Section: Immunological/physiological Barriermentioning

confidence: 95%

Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions

Anchordoquy,

Artzi,

Balyasnikova

et al. 2024

ACS Nano

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In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop "Mechanisms and Barriers in Nanomedicine" in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, and students to trigger ideas and concepts to move the field forward.

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Section: Immunological/physiological Barriermentioning

confidence: 95%

Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions

Anchordoquy,

Artzi,

Balyasnikova

et al. 2024

ACS Nano

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show abstract

A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics

Ranjbar,

Zhong,

Manautou

et al. 2023

Advanced Drug Delivery Reviews

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Exploiting a Type III Interferon Response to Improve Chemotherapeutic Safety and Efficacy

TILDEN,

Ricco,

Hemann

et al. 2024

Preprint

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Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase the efficacy of chemotherapeutic nanomedicines. In this study we sought to clarify which cell type(s) are capable of producing IFN-λ in response to lipoplexes and how the effects of IFN-λ are propagated. Additionally, we demonstrate that an IFN-λ pretreatment is also capable of altering the accumulation profile of small molecules like doxorubicin. Finally, we assessed different administration routes for an IFN-λ pretreatment and showed the ability of this pretreatment to significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.

show abstract

Reducing off-target drug accumulation by exploiting a type-III interferon response

Cited by 3 publications

References 77 publications

Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions

Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions

A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics

Exploiting a Type III Interferon Response to Improve Chemotherapeutic Safety and Efficacy

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