Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

Ma, Hong; Xing, Fei; Zhou, Yue; Yu, Peiyun; Luo, Rong; Xu, Jiawei; Xiang, Zhou; Rommens, Pol Maria; Duan, Xin; Ritz, Ulrike

doi:10.1039/d3tb01008b

Cited by 2 publications

(1 citation statement)

References 374 publications

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“…Macrophage or phagocytic capture reduces particle circulation in blood. Developing immune-invasive coating can prevent immune recognition and reduce macrophage capture, enhancing the NPs circulation in the blood [8,9]. Vegas et al discovered a triazole containing a small molecule (RZA15) through a combinatorial screening approach that [10] leads to reduction of the recruitment and attachment of the macrophages [11].…”

Section: Introductionmentioning

confidence: 99%

Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles

Yenurkar,

Ruocco,

Pragya

et al. 2024

Biomed. Mater.

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Nanomedicine often failed clinically to show therapeutic efficacy due to reduced particle circulation and enhanced capture by the reticuloendothelial system (RES), including the liver. Developing novel immunomodulatory surface coating can prevent macrophage capture and increase the particle circulation of the nanomedicine, resulting in higher therapeutic efficiency. Herein, we demonstrate the development of immunomodulatory small molecule (RZA15) with triazole functionality using copper-catalyzed click chemistry to conjugate onto spherical polystyrene nanoparticles using amide coupling reactions, achieving higher blood circulation and lesser macrophage uptake of the nanoconjugates. In this work, we evaluated the effectiveness of RZA15 coating for the enhanced circulation of polystyrene nanoparticles of 100 nm size, which is commonly utilized for various drug delivery applications, and compared with poly(ethylene)glycol (PEG) coatings. Several polystyrene nanoconjugate formulations were analyzed in vitro in normal and macrophage cells for cell viability and cellular uptake studies. In vitro studies demonstrated lesser macrophage uptake of the nanoconjugates following RZA15 coating. Finally, in vivo, blood-circulation, pharmacokinetics, and biodistribution studies were performed in the C57BL/6J mouse model that endorsed the substantial role of RZA15 in preventing liver and spleen capture and results in extended circulation. Coating immunomodulatory small molecules to nanoparticles can severely enhance the potential therapeutic effects of nanomedicine at lower doses.

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Section: Introductionmentioning

confidence: 99%

Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles

Yenurkar,

Ruocco,

Pragya

et al. 2024

Biomed. Mater.

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Laser-Induced Intracellular Delivery: Exploiting Gold-Coated Spiky Polymeric Nanoparticles and Gold Nanorods under Near-Infrared Pulses for Single-Cell Nano-Photon-Poration

Kumar,

Nahak,

Gupta

et al. 2024

Micromachines

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This study explores the potential of laser-induced nano-photon-poration as a non-invasive technique for the intracellular delivery of micro/macromolecules at the single-cell level. This research proposes the utilization of gold-coated spiky polymeric nanoparticles (Au-PNPs) and gold nanorods (GNRs) to achieve efficient intracellular micro/macromolecule delivery at the single-cell level. By shifting the operating wavelength towards the near-infrared (NIR) range, the intracellular delivery efficiency and viability of Au-PNP-mediated photon-poration are compared to those using GNR-mediated intracellular delivery. Employing Au-PNPs as mediators in conjunction with nanosecond-pulsed lasers, a highly efficient intracellular delivery, while preserving high cell viability, is demonstrated. Laser pulses directed at Au-PNPs generate over a hundred hot spots per particle through plasmon resonance, facilitating the formation of photothermal vapor nanobubbles (PVNBs). These PVNBs create transient pores, enabling the gentle transfer of cargo from the extracellular to the intracellular milieu, without inducing deleterious effects in the cells. The optimization of wavelengths in the NIR region, coupled with low laser fluence (27 mJ/cm2) and nanoparticle concentrations (34 µg/mL), achieves outstanding delivery efficiencies (96%) and maintains high cell viability (up to 99%) across the various cell types, including cancer and neuronal cells. Importantly, sustained high cell viability (90–95%) is observed even 48 h post laser exposure. This innovative development holds considerable promise for diverse applications, encompassing drug delivery, gene therapy, and regenerative medicine. This study underscores the efficiency and versatility of the proposed technique, positioning it as a valuable tool for advancing intracellular delivery strategies in biomedical applications.

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Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

Abstract: Intracellular cargo delivery, the introduction of small molecules, proteins, and nucleic acids into a specific targeted site in a biological system, is an important strategy for deciphering cell function, directing...

Cited by 2 publications

References 374 publications

Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles

Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles

Laser-Induced Intracellular Delivery: Exploiting Gold-Coated Spiky Polymeric Nanoparticles and Gold Nanorods under Near-Infrared Pulses for Single-Cell Nano-Photon-Poration

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