The structural fate of lipid nanoparticles in the extracellular matrix

Bandara, Sarith R.; Molley, Thomas G.; Kim, Hojun; Bharath, P.; Kilian, Kristopher A.; Leal, Cecília

doi:10.1039/c9mh00835g

Cited by 21 publications

(18 citation statements)

References 77 publications

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“…For example, SAXS has been recently used to study the structural fate of lipid nanoparticles in the ECM. 74 We have also shown in previous work that in situ monitoring of the AuNPs transformation inside cells was enabled by SAXS. 12 This SAXS study was performed on three types of polymergrafted NPs: PMAA(7)-AuNPs, PMAA(11)-AuNPs, and PMAA(19)-AuNPs.…”

Section: ■ Results and Discussionsupporting

confidence: 57%

How Do Surface Properties of Nanoparticles Influence Their Diffusion in the Extracellular Matrix? A Model Study in Matrigel Using Polymer-Grafted Nanoparticles

et al. 2020

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Diffusion of nanomedicines inside the extracellular matrix (ECM) has been identified as a key factor to achieve homogeneous distribution and therefore therapeutic efficacy. Here, we sought to determine the impact of nanoparticles’ (NPs) surface properties on their ability to diffuse in the ECM. As model nano-objects, we used a library of gold nanoparticles grafted with a versatile polymethacrylate corona, which enabled the surface properties to be modified. To accurately recreate the features of the native ECM, diffusion studies were carried out in a tumor-derived gel (Matrigel). We developed two methods to evaluate the diffusion ability of NPs inside this model gel: an easy-to-implement one based on optical monitoring and another one using small-angle X-ray scattering (SAXS) measurements. Both enabled the determination of the diffusion coefficients of NPs and comparison of the influence of their various surface properties, while the SAXS technique also allowed to monitor the NPs’ structure as they diffused inside the gel. Positive charges and hydrophobicity were found to particularly hinder diffusion, and the different results suggested on the whole the presence of NPs–matrix interactions, therefore underlying the importance of the ECM model. The accuracy of the tumor-derived gels used in this study was evidenced by in vivo experiments involving intratumoral injections of NPs on mice, which showed that diffusion patterns in the peripheral tumor tissues were quite similar to the ones obtained within the chosen ECM model.

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Section: ■ Results and Discussionsupporting

confidence: 57%

How Do Surface Properties of Nanoparticles Influence Their Diffusion in the Extracellular Matrix? A Model Study in Matrigel Using Polymer-Grafted Nanoparticles

et al. 2020

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“…This may be attributed to the inefficient release of liposomes decreasing the antitumor performance of BF211@Lipo. 42 Additionally, the uptake of BF211@Lipo was evaluated on normal Raw 264.7 macrophages and HepG2 tumor cells ( Figure S3B and C ). The results indicated that BF211@Lipo were more ingested by tumor cells, showing a certain cell selectivity, which would be beneficial to reduce phagocytosis and toxicity to normal cells, enhancing the specific antitumor therapeutic effect.…”

Section: Resultsmentioning

confidence: 99%

Surfactant Assisted Rapid-Release Liposomal Strategies Enhance the Antitumor Efficiency of Bufalin Derivative and Reduce Cardiotoxicity

Gao¹,

Zhang²,

He³

et al. 2021

IJN

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Background: BF211, a derivative of bufalin (BF), shows significantly improved solubility and potent antitumor efficiency compared to BF. Unfortunately, the unwanted toxicity such as cardiotoxicity caused by unspecific distribution has hindered its clinical use. Methods: PEGylated BF211 liposomes (BF211@Lipo) were designed and optimizely prepared based on the pre-prescription research. In vitro and in vivo cardiotoxicity was evaluated. In vivo pharmacokinetics and biodistribution of BF211@Lipo were investigated. In vivo antitumor activity and toxicity were evaluated in HepG2 cell xenograft models. The rapid-release triggered by Poloxamer 188 (P188) was assessed in vitro and in vivo. Results: The optimized BF211@Lipo displayed a spherical morphology with a size of (164.6 ± 10.3) nm and a high encapsulation efficiency of (93.24 ± 2.15) %. The in vivo concentration-time curves of BF211 loaded in liposomes showed a prolonged half-life in plasma and increased tumor accumulation. No obvious abnormality in electrocardiograms was observed in guinea pigs even at 9 mg/kg. Moreover, to improve the efficient release of BF211@Lipo, a surfactant-assisted rapid-release strategy was developed, and the releasepromoting mechanism was revealed by the fluorescence resonance energy transfer (FRET) and fluorescence nanoparticle tracking analysis (fl-NTA) technology. Sequential injection of BF211@Lipo and P188 could ignite the "cold" liposomes locally in tumor regions, facilitating the burst release of BF211 and enhancing the therapeutic index. Conclusion: Our progressive efforts that begin with preparation technology and dosage regimen enable BF211 to like a drug, providing a promising nano platform to deliver the cardiac glycosides and alleviate the side effects by decreasing unspecific biodistribution.

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“…[13][14][15][16][17][18][19] Such functional supramolecular polymers feature properties beyond the classical role of DNA in biological systems, with applications in optoelectronic devices, drug delivery systems, and diagnostics to name a few. [20][21][22][23][24][25][26][27][28] However, vesicular morphologies are predominantly reported from lipid-DNA conjugates or DNA functionalized liposomes, [29][30][31][32][33][34] while the field apart from lipid-based DNA constructs remains largely unexplored. 35 In previous work, we demonstrated the self-assembly of phenanthrene-DNA conjugates into vesicular structures with light-harvesting features.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular assembly of DNA-constructed vesicles

et al. 2020

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The structural fate of lipid nanoparticles in the extracellular matrix

Abstract: Hydrogels cause unilamellar liposomes to transform into aggregates of multilamellar structures through an osmotic effect.

Cited by 21 publications

References 77 publications

How Do Surface Properties of Nanoparticles Influence Their Diffusion in the Extracellular Matrix? A Model Study in Matrigel Using Polymer-Grafted Nanoparticles

How Do Surface Properties of Nanoparticles Influence Their Diffusion in the Extracellular Matrix? A Model Study in Matrigel Using Polymer-Grafted Nanoparticles

Surfactant Assisted Rapid-Release Liposomal Strategies Enhance the Antitumor Efficiency of Bufalin Derivative and Reduce Cardiotoxicity

Supramolecular assembly of DNA-constructed vesicles

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