Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

Bisso, Sofia; Mura, Simona; Castagner, Bastien; Couvreur, Patrick; Leroux, Jean‐Christophe

doi:10.1016/j.ejpb.2019.06.013

Cited by 21 publications

(8 citation statements)

References 59 publications

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“…Synthesis of PEG-Ale and Alex Fluor 488-Ale: PEG-Ale was synthetized according to a reported method with minor modification. [28] Ale (400 mg, 1.23 mmol) was dissolved in NaOH solution (2 n, 1 mL), followed by adding ultrapure H 2 O (800 μL, 18.2 MΩ cm). The pH value of the solution was adjusted to 7 by dropwise addition of HCl (1 n).…”

Section: Methodsmentioning

confidence: 99%

A Manganese Phosphate Nanocluster Activates the cGAS‐STING Pathway for Enhanced Cancer Immunotherapy

Gao

Xie

Lei

et al. 2021

Advanced Therapeutics

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Targeting the stimulator of interferon genes (STING) pathway with cyclic dinucleotides (CDNs), the natural STING agonists, is a promising immunotherapeutic strategy for cancer. However, the clinical application of natural CDNs as therapeutics is greatly hindered by their intrinsic properties including negative charges, small molecular weight, and high susceptibility to enzymatic degradation. Mn 2+ ions have been recently discovered to directly activate the cyclic GMP-AMP (cGAMP) synthase (cGAS) and augment cGAMP-STING binding affinity. Here, a PEGylated manganese(II) phosphate (MnP-PEG) nanocluster is developed with high biocompatibility and potent capacity to stimulate the cGAS-STING pathway. MnP-PEG nanoclusters activate the immature bone marrow-derived dendritic cells (DCs) leading to 57.3-and 13.3-fold higher production of interferon and interleukin-6 than free cGAMP, respectively. The potent STING activation capacity is likely due to the efficient cellular internalization of MnP-PEG nanoclusters by DCs and acid-triggered release of Mn 2+ ions in the endolysosomes. Intratumoral administration of MnP-PEG nanoclusters markedly enhances tumor infiltration as well as maturation of DCs and macrophages, and promotes activation and cytotoxicity of T cells and natural killer cells in the tumor. MnP-PEG nanocluster in combination with a checkpoint inhibitor leads to significant tumor regression in the B16F10 murine melanoma model without any overt toxicities.

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Section: Methodsmentioning

confidence: 99%

A Manganese Phosphate Nanocluster Activates the cGAS‐STING Pathway for Enhanced Cancer Immunotherapy

Gao

Xie

Lei

et al. 2021

Advanced Therapeutics

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“…For example, Madhumathi et al used calcium phosphate nanoparticles for the co-delivery of the antibiotic, tetracycline and the anti-inflammatory, ibuprofen [36]. Bisso et al used a similar approach for the dual delivery of bisphosphates and nucleic acids [37]. Therapeutic factors can be loaded onto calcium phosphate particles either during the synthesis of the calcium phosphate through co-precipitation [38,39,40] or by combining with the calcium phosphate powders post-synthesis through absorption processes [36].…”

Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

“…Bisphosphonate-loaded calcium phosphate particles have also been used in dual drug delivery approaches. For example, Bisso et al investigated the dual delivery of plasmid DNA and alendronate using calcium phosphate nanoparticles, with the goal of facilitating cellular internalization of both the compounds and potentially achieving a combined pharmacological effect [37]. The study used a pH-sensitive poly(ethylene glycol)-alendronate conjugate to formulate stable plasmid DNA-loaded calcium phosphate nanoparticles.…”

Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

2019

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Bone injuries and diseases constitute a burden both socially and economically, as the consequences of a lack of effective treatments affect both the patients’ quality of life and the costs on the health systems. This impended need has led the research community’s efforts to establish efficacious bone tissue engineering solutions. There has been a recent focus on the use of biomaterial-based nanoparticles for the delivery of therapeutic factors. Among the biomaterials being considered to date, calcium phosphates have emerged as one of the most promising materials for bone repair applications due to their osteoconductivity, osteoinductivity and their ability to be resorbed in the body. Calcium phosphate nanoparticles have received particular attention as non-viral vectors for gene therapy, as factors such as plasmid DNAs, microRNAs (miRNA) and silencing RNA (siRNAs) can be easily incorporated on their surface. Calcium phosphate nanoparticles loaded with therapeutic factors have also been delivered to the site of bone injury using scaffolds and hydrogels. This review provides an extensive overview of the current state-of-the-art relating to the design and synthesis of calcium phosphate nanoparticles as carriers for therapeutic factors, the mechanisms of therapeutic factors’ loading and release, and their application in bone tissue engineering.

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“…The use of calcium phosphate compounds as inherent entities in bone void fillers or scaffold materials aimed at tissue engineering has recently gained considerable interest. Several reports on novel materials containing calcium phosphate nanoparticles elucidate their potential [21][22][23][24][25][26][27]. The inorganic phase incorporated within an organic carrier may act beneficially in terms of osteogenic commitment; for example, fibroblast-derived extracellular matrix (ECM) sheets for the replacement of the periosteum promoted osteogenic differentiation of human mesenchymal stem cells (MSCs) [28] when covered with calcium phosphate particles.…”

Section: Introductionmentioning

confidence: 99%

Directing Stem Cell Commitment by Amorphous Calcium Phosphate Nanoparticles Incorporated in PLGA: Relevance of the Free Calcium Ion Concentration

Gröninger

Hess

Mohn

et al. 2020

IJMS

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The microenvironment of mesenchymal stem cells (MSCs) is responsible for the modulation in MSC commitment. Nanocomposites with an inorganic and an organic component have been investigated, and osteogenesis of MSCs has been attributed to inorganic phases such as calcium phosphate under several conditions. Here, electrospun meshes and two-dimensional films of poly(lactic-co-glycolic acid) (PLGA) or nanocomposites of PLGA and amorphous calcium phosphate nanoparticles (PLGA/aCaP) seeded with human adipose-derived stem cells (ASCs) were analyzed for the expression of selected marker genes. In a two-week in vitro experiment, osteogenic commitment was not found to be favored on PLGA/aCaP compared to pure PLGA. Analysis of the medium revealed a significant reduction of the Ca2+ concentration when incubated with PLGA/aCaP, caused by chemical precipitation of hydroxyapatite (HAp) on aCaP seeds of PLGA/aCaP. Upon offering a constant Ca2+ concentration, however, the previously observed anti-osteogenic effect was reversed: alkaline phosphatase, an early osteogenic marker gene, was upregulated on PLGA/aCaP compared to pristine PLGA. Hence, in addition to the cell–material interaction, the material–medium interaction was also important for the stem cell commitment here, affecting the cell–medium interaction. Complex in vitro models should therefore consider all factors, as coupled impacts might emerge.

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Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

Cited by 21 publications

References 59 publications

A Manganese Phosphate Nanocluster Activates the cGAS‐STING Pathway for Enhanced Cancer Immunotherapy

A Manganese Phosphate Nanocluster Activates the cGAS‐STING Pathway for Enhanced Cancer Immunotherapy

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

Directing Stem Cell Commitment by Amorphous Calcium Phosphate Nanoparticles Incorporated in PLGA: Relevance of the Free Calcium Ion Concentration

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