Generation of antigen-specific Foxp3+ regulatory T-cells in vivo following administration of diabetes-reversing tolerogenic microspheres does not require provision of antigen in the formulation

Engman, Carl; Wen, Yi; Meng, Wilson S.; Bottino, Rita; Trucco, Massimo; Giannoukakis, Nick

doi:10.1016/j.clim.2015.03.004

Cited by 58 publications

(42 citation statements)

References 110 publications

(6 reference statements)

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“…However, although systematic comparisons between the in vitro and in vivo behaviors of ENPBs are important before they are evaluated in the clinic, such comparisons were not made in our previous work Polymer materials have been widely used as biomedical materials. [27][28][29][30][31] Many synthetic polymer biomaterials similar to P(DLLA-CL), such as PDLLA, [32][33][34][35] PLGA, 36-37 P(LLA-CL), 38 and PCL, [39][40] have been assessed in vivo to determine their behaviors in the bone microenvironments of sheep, [32][33][35][36] rabbit, 34,37 and pig. [38][39][40] However, there have been no reports evaluating the in vivo behaviors of P(DLLA-CL) biomaterials in bone microenvironments thus far.…”

Section: Introductionmentioning

confidence: 99%

Electrospun Nanofibrous P(DLLA–CL) Balloons as Calcium Phosphate Cement Filled Containers for Bone Repair: in Vitro and in Vivo Studies

Liu

Wei

Zhong

et al. 2015

ACS Appl. Mater. Interfaces

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The spinal surgeon community has expressed significant interest in applying calcium phosphate cement (CPC) for the treatment of vertebral compression fractures (VCFs) and minimizing its disadvantages, such as its water-induced collapsibility and poor mechanical properties, limiting its clinical use. In this work, novel biodegradable electrospun nanofibrous poly(d,l-lactic acid-ϵ-caprolactone) balloons (ENPBs) were prepared, and the separation, pressure, degradation, and new bone formation behaviors of the ENPBs when used as CPC-filled containers in vitro and in vivo were systematically analyzed and compared. CPC could be separated from surrounding bone tissues by ENPBs in vitro and in vivo. ENPB-CPCs (ENPBs serving as CPC-filled containers) exerted pressure on the surrounding bone microenvironment, which was enough to crush trabecular bone. Compared with the CPC implantation, ENPB-CPCs delayed the degradation of CPC (i.e., its water-induced collapsilibity). Finally, possible mechanisms behind the in vivo effects caused by ENPB-CPCs implanted into rabbit thighbones and pig vertebrae were proposed. This work suggests that ENPBs can be potentially applied as CPC-filled containers in vivo and provides an experimental basis for the clinical application of ENPBs for the treatment of VCFs. In addition, this work will be of benefit to the development of polymer-based medical implants in the future.

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Section: Introductionmentioning

confidence: 99%

Electrospun Nanofibrous P(DLLA–CL) Balloons as Calcium Phosphate Cement Filled Containers for Bone Repair: in Vitro and in Vivo Studies

Liu

Wei

Zhong

et al. 2015

ACS Appl. Mater. Interfaces

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“…By concentrating antibodies in lymph nodes to which inflamed tissues drained, dosage of the drug injected can be reduced. Techniques of parental injections targeting selected lymph nodes have been reported [41]. The current design hinges on engineering a fluorogenic module into the network of βFP within which binding sites for IgG can be monitored optically (Fig.…”

Section: Resultsmentioning

confidence: 99%

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

Liu

Saunders

Bagia

et al. 2016

Journal of Controlled Release

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Herein we report an injectable film by which antibodies can be localized in vivo. The system builds upon a bifunctional polypeptide consisting of a fluorogen-activating protein (FAP) and a β-fibrillizing peptide (βFP). The FAP domain generates fluorescence that reflects IgG binding sites conferred by Protein A/G (pAG) conjugated with the fluorogen malachite green (MG). A film is generated by mixing these proteins with molar excess of EAK16-II, a βFP that forms β-sheet fibrils at high salt concentrations. The IgG-binding, fluorogenic film can be injected in vivo through conventional needled syringes. Confocal microscopic images and dose–response titration experiments showed that loading of IgG into the film was mediated by pAGMG bound to the FAP. Release of IgG in vitro was significantly delayed by the bioaffinity mechanism; 26% of the IgG were released from films embedded with pAGMG after five days, comparedto close to 90% in films without pAGMG. Computational simulations indicated that the release rate of IgG is governed by positive cooperativity due to pAGMG. When injected into the subcutaneous space of mouse footpads, film-embedded IgG were retained locally, with distribution through the lymphatics impeded. The ability to track IgG binding sites and distribution simultaneously will aid the optimization of local antibody delivery systems.

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“…Recent work by the Giannoukakis laboratory established microparticles containing antisense oligonucleotides against CD40, CD80, and CD86 co-stimulatory molecule transcripts can combinatorially downregulate DC maturation and ameliorate disease in a type 1 diabetes mouse model, laying the foundation for the DC-based clinical trial mentioned above. Upon subcutaneous injection, microparticles were shown to be taken up by DCs, traffic to draining lymph nodes, augment antigen-specific regulatory T cell proliferation, and reverse new-onset diabetes [46,47]. …”

Section: Targeted Drug Delivery To Immune Cellsmentioning

confidence: 99%

Combinatorial drug delivery approaches for immunomodulation

Stewart

Keselowsky

2017

Advanced Drug Delivery Reviews

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Immunotherapy has been widely explored for applications to both augment and suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an individual arm of the immune system are often incompletely effective. Imperfect mechanistic understanding and heterogeneity within disease pathology have seen monotherapies inadequately equipped to mediate complete disease remission. Recent success in applications of combinatorial immunotherapy has suggested that targeting multiple biological pathways simultaneously may be critical in treating complex immune pathologies. Drug delivery approaches through engineered biomaterials offer the potential to augment desired immune responses while mitigating toxic side-effects by localizing immunotherapy. This review discusses recent advances in immunotherapy and highlights newly explored combinatorial drug delivery approaches. Furthermore, prospective future directions for immunomodulatory drug delivery to exploit are provided.

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Generation of antigen-specific Foxp3+ regulatory T-cells in vivo following administration of diabetes-reversing tolerogenic microspheres does not require provision of antigen in the formulation

Cited by 58 publications

References 110 publications

Electrospun Nanofibrous P(DLLA–CL) Balloons as Calcium Phosphate Cement Filled Containers for Bone Repair: in Vitro and in Vivo Studies

Electrospun Nanofibrous P(DLLA–CL) Balloons as Calcium Phosphate Cement Filled Containers for Bone Repair: in Vitro and in Vivo Studies

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

Combinatorial drug delivery approaches for immunomodulation

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