Improved nanoformulation and bio-functionalization of linear-dendritic block copolymers with biocompatible ionic liquids

Hamadani, Christine M.; Chandrasiri, Indika; Yaddehige, Mahesh Loku; Dasanayake, Gaya S.; Owolabi, Iyanuoluwani; Flynt, Alex S.; Hossain, Mehjabeen; Liberman, Lucy; Lodge, Timothy P.; Werfel, Thomas A.; Watkins, Davita L.; Tanner, Eden E. L.

doi:10.1039/d2nr00538g

Cited by 23 publications

(26 citation statements)

References 44 publications

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“…Hemo-Biocompatibility Studies: Hemolysis assay to check potential red blood cell viability in the presence of NPs was simulated exvivo in accordance with previously published methods, however in this case with K2-EDTA-treated female adult human whole blood (Bio-IVT, #HMN796643). [41,42] Whole blood was mixed with 4 mg mL −1 of PMAG or PEGMA NPs in 1x phosphate-buffered saline (PBS) pH 7.4, 1 mg mL −1 of PLGA NPs in 1x PBS pH 7.4, 1x PBS pH 7.4, or Triton-X (20% v/v). Hemolysis assay was performed in quadruplicate and absorbance was measured at 405 nm (BioTeK synergy H1).…”

Section: Methodsmentioning

confidence: 99%

“…Hemo-biocompatibility was performed as previously published [41,42] to assess the nanoparticles' suitability for intravenous administration. Figure 3B shows the degree of lysis of RBC membranes after physical interaction with nanoparticles.…”

Section: Cytocompatibility Studiesmentioning

confidence: 99%

“…1 mg mL −1 PLGA NPs provided as reference polymer as previously published. [41,42] C) Percentage of early apoptotic cells after treatment with nanoparticles. D) Percentage of late apoptotic cells after treatment with nanoparticles.…”

Section: Cytocompatibility Studiesmentioning

confidence: 99%

“…A) Cell viability of naïve RAW 264.7 macrophages after incubating with varying concentrations of PPSb-PMAG and PPS-b-PEGMA for 24 h. B) Average ex vivo red blood cell (RBC) hemolysis assays with PPS-b-PMAG and PPS-b-PEGMA show high human hemo-biocompatibility (n = 4 with mean standard error).20% v/v Triton-X and 1x PBS were used as positive and negative normalization controls. 1 mg mL −1 PLGA NPs provided as reference polymer as previously published [41,42]. C) Percentage of early apoptotic cells after treatment with nanoparticles.…”

mentioning

confidence: 99%

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ROS‐Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

Shofolawe-Bakare

Mel

Mishra

et al. 2022

Macromolecular Bioscience

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Macrophages play a diverse, key role in many pathologies, including inflammatory diseases, cardiovascular diseases, and cancer. However, many therapeutic strategies targeting macrophages suffer from systemic off-target toxicity resulting in notoriously narrow therapeutic windows. To address this shortcoming, the development of poly(propylene sulfide)-b-poly(methacrylamidoglucopyranose) [PPS-b-PMAG] diblock copolymer-based nanoparticles (PMAG NPs) capable of targeting macrophages and releasing drug in the presence of reactive oxygen species (ROS) is reported. PMAG NPs have desirable physicochemical properties for systemic drug delivery, including slightly negative surface charge, ≈100 nm diameter, and hemo-compatibility. Additionally, due to the presence of PPS in the NP core, PMAG NPs release drug cargo preferentially in the presence of ROS. Importantly, PMAG NPs display high cytocompatibility and are taken up by macrophages in cell culture at a rate ≈18-fold higher than PEGMA NPs-NPs composed of PPS-b-poly(oligoethylene glycol methacrylate). Computational studies indicate that PMAG NPs likely bind with glucose transporters such as GLUT 1/3 on the macrophage cell surface to facilitate high levels of internalization. Collectively, this study introduces glycopolymeric NPs that are uniquely capable of both receptor-ligand targeting to macrophages and ROS-dependent drug release and that can be useful in many immunotherapeutic settings.

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Section: Methodsmentioning

confidence: 99%

Section: Cytocompatibility Studiesmentioning

confidence: 99%

Section: Cytocompatibility Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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ROS‐Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

Shofolawe-Bakare

Mel

Mishra

et al. 2022

Macromolecular Bioscience

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“…The method involves the use of living cells ( biological-camouflage of the nanoparticles, thereby preventing opsonization. 91,92 Biological camouflage (biomimicry) is a strategy utilized in the prevention of opsonization of nanoparticles. This strategy involves modification of the nanoparticulate surface to mimic the properties of biological molecules, such as cell, cell membranes, or macromolecular-proteins, that are not recognized by the immune system as foreign.…”

Section: Cellular Hitchhikingmentioning

confidence: 99%

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Mehta,

Shende

2023

Cell Biochemistry & Function

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Opsonization plays a pivotal role in hindering controlled drug release from nanoformulations due to macrophage‐mediated nanoparticle destruction. While first and second‐generation delivery systems, such as lipoplexes (50–150 nm) and quantum dots, hold immense potential in revolutionizing disease treatment through spatiotemporal controlled drug delivery, their therapeutic efficacy is restricted by the selective labeling of nanoparticles for uptake by reticuloendothelial system and mononuclear phagocyte system via various molecular forces, such as electrostatic, hydrophobic, and van der Waals bonds. This review article presents novel insights into surface‐modification techniques utilizing macromolecule‐mediated approaches, including PEGylation, di‐block copolymerization, and multi‐block polymerization. These techniques induce stealth properties by generating steric forces to repel micromolecular‐opsonins, such as fibrinogen, thereby mitigating opsonization effects. Moreover, advanced biological methods, like cellular hitchhiking and dysopsonic protein adsorption, are highlighted for their potential to induce biological camouflage by adsorbing onto the nanoparticulate surface, leading to immune escape. These significant findings pave the way for the development of long‐circulating next‐generation nanoplatforms capable of delivering superior therapy to patients. Future integration of artificial intelligence‐based algorithms, integrated with nanoparticle properties such as shape, size, and surface chemistry, can aid in elucidating nanoparticulate‐surface morphology and predicting interactions with the immune system, providing valuable insights into the probable path of opsonization.

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Ionic Liquid Coating‐Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV

Hamadani,

Mahdi,

Merrell

et al. 2024

Advanced Science

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Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, the CNS acts as a latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate HIV, and given CNS infection, patients experience neurological deficits collectively referred to as “neuroHIV”. Herein, the development of bioinspired ionic liquid‐coated nanoparticles (IL‐NPs) for in situ hitchhiking on red blood cells (RBCs) is reported, which enables 48% brain delivery of intracarotid arterial‐ infused cargo. Moreover, IL choline trans‐2‐hexenoate (CA2HA 1:2) demonstrates preferential accumulation in parenchymal microglia over endothelial cells post‐delivery. This study further demonstrates successful loading of abacavir (ABC), an ART that is challenging to encapsulate, into IL‐NPs, and verifies retention of antiviral efficacy in vitro. IL‐NPs are not cytotoxic to primary human peripheral blood mononuclear cells (PBMCs) and the CA2HA 1:2 coating itself confers notable anti‐viremic capacity. In addition, in vitro cell culture assays show markedly increased uptake of IL‐NPs into neural cells compared to bare PLGA nanoparticles. This work debuts bioinspired ionic liquids as promising nanoparticle coatings to assist CNS biodistribution and has the potential to revolutionize the delivery of cargos (i.e., drugs, viral vectors) through compartmental barriers such as the blood‐brain‐barrier (BBB).

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Improved nanoformulation and bio-functionalization of linear-dendritic block copolymers with biocompatible ionic liquids

Abstract: Ionic liquid-functionalized linear-dendritic block copolymer nanoparticles show facile assemblies and red blood cell hitchhiking in whole blood.

Cited by 23 publications

References 44 publications

ROS‐Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

ROS‐Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Ionic Liquid Coating‐Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV

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