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Insight into the preformed albumin corona on in vitro and in vivo performances of albumin-selective nanoparticles.

ABSTRACT: Preformed albumin corona of albumin-nonselective nanoparticles (NPs) is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration. However, very few studies have concerned the preformed albumin corona of albumin-selective NPs. Herein, we report a novel type of albumin-selective NPs by decorating 6-maleimidocaproyl polyethylene glycol stearate (SA) onto PLGA NPs (SP NPs) surface, taking albumin-nonselective PLGA NPs as control. PLGA NPs and SP NPs were prepared by emulsion-solvent evaporation method and the resultant NPs were in spherical shape with an average diameter around 180?nm. The corresponding albumin-coating PLGA NPs (PLGA@BSA NPs) and albumin-coating SP NPs (SP@BSA NPs) were formulated by incubating SP NPs or PLGA NPs with bovine serum albumin solution, respectively. The impact of albumin corona on particle characteristics, stability, photothermal effect, cytotoxicity, cell uptake, spheroid penetration and pharmacokinetics was investigated. In line with previous findings of preformed albumin coating, PLGA@BSA NPs exhibited higher stability, cytotoxicity, cell internalization and spheroid penetration performances in vitro, and longer blood circulation time in vivo than those of albumin-nonselective PLGA NPs, but albumin-selective SP NPs is capable of achieving a comparable in vitro and in vivo performances with both SP@BSA NPs and PLGA@BSA NPs. Our results demonstrate that SA decorated albumin-selective NPs pave a versatile avenue for optimizing nanoparticulate delivery without preformed albumin corona.

SUBMITTER: Li Z

PROVIDER: S-EPMC7032257 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Insight into the preformed albumin corona on <i>in vitro</i> and <i>in vivo</i> performances of albumin-selective nanoparticles.

Li Zhenbao Z Li Dan D Zhang Wenjuan W Zhang Peng P Kan Qiming Q Sun Jin J

Asian journal of pharmaceutical sciences 20180809 1

Preformed albumin corona of albumin-nonselective nanoparticles (NPs) is widely exploited to inhibit the unavoidable protein adsorption upon intravenous administration. However, very few studies have concerned the preformed albumin corona of albumin-selective NPs. Herein, we report a novel type of albumin-selective NPs by decorating 6-maleimidocaproyl polyethylene glycol stearate (SA) onto PLGA NPs (SP NPs) surface, taking albumin-nonselective PLGA NPs as control. PLGA NPs and SP NPs were prepare ...[more]

PMID: 32104438

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Project description:Numerous nanocarriers of small molecules depend on either non-specific physical encapsulation or direct covalent linkage. In contrast, this manuscript explores an alternative encapsulation strategy based on high-specificity avidity between a small molecule drug and its cognate protein target fused to the corona of protein polymer nanoparticles. With the new strategy, the drug associates tightly to the carrier and releases slowly, which may decrease toxicity and promote tumor accumulation via the enhanced permeability and retention effect. To test this hypothesis, the drug Rapamycin (Rapa) was selected for its potent anti-proliferative properties, which give it immunosuppressant and anti-tumor activity. Despite its potency, Rapa has low solubility, low oral bioavailability, and rapid systemic clearance, which make it an excellent candidate for nanoparticulate drug delivery. To explore this approach, genetically engineered diblock copolymers were constructed from elastin-like polypeptides (ELPs) that assemble small (<100nm) nanoparticles. ELPs are protein polymers of the sequence (Val-Pro-Gly-Xaa-Gly)n, where the identity of Xaa and n determine their assembly properties. Initially, a screening assay for model drug encapsulation in ELP nanoparticles was developed, which showed that Rose Bengal and Rapa have high non-specific encapsulation in the core of ELP nanoparticles with a sequence where Xaa=Ile or Phe. While excellent at entrapping these drugs, their release was relatively fast (2.2h half-life) compared to their intended mean residence time in the human body. Having determined that Rapa can be non-specifically entrapped in the core of ELP nanoparticles, FK506 binding protein 12 (FKBP), which is the cognate protein target of Rapa, was genetically fused to the surface of these nanoparticles (FSI) to enhance their avidity towards Rapa. The fusion of FKBP to these nanoparticles slowed the terminal half-life of drug release to 57.8h. To determine if this class of drug carriers has potential applications in vivo, FSI/Rapa was administered to mice carrying a human breast cancer model (MDA-MB-468). Compared to free drug, FSI encapsulation significantly decreased gross toxicity and enhanced the anti-cancer activity. In conclusion, protein polymer nanoparticles decorated with the cognate receptor of a high potency, low solubility drug (Rapa) efficiently improved drug loading capacity and its release. This approach has applications to the delivery of Rapa and its analogs; furthermore, this strategy has broader applications in the encapsulation, targeting, and release of other potent small molecules.

Dataset Information

Insight into the preformed albumin corona on in vitro and in vivo performances of albumin-selective nanoparticles.

Publications

Insight into the preformed albumin corona on <i>in vitro</i> and <i>in vivo</i> performances of albumin-selective nanoparticles.

Similar Datasets

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