A poly(beta-amino ester) activates macrophages independent of NF-κB signaling

Dold, Neil M.; Zeng, Qin; Zeng, Xianyi; Jewell, Christopher M.

doi:10.1016/j.actbio.2017.12.040

Cited by 29 publications

(23 citation statements)

References 44 publications

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“…These polymers have a unique branched architecture that provides a large chemical space for complexation and functionalization. Due to their cationic properties, poly(beta-amino esters) enhances cellular uptake and endosomal escape via the proton sponge effect 224 , 225 . Polymeric nanocarriers can provide effective solutions to these obstacles, and degradable polymers used for cancer vaccines are summarized in Table 3 .…”

Section: Nanocarrier-driven Immunomodulatory Approaches For Pdacmentioning

confidence: 99%

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Liu¹,

Kshirsagar²,

Gautam³

et al. 2022

Theranostics

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Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.

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Section: Nanocarrier-driven Immunomodulatory Approaches For Pdacmentioning

confidence: 99%

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Liu¹,

Kshirsagar²,

Gautam³

et al. 2022

Theranostics

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“…The Jewell group has reported that, while free PBAE in solution is immunologically inert, PBAEs complexed with a polyanion to form nanoparticles can cause activation of antigen-presenting cells (APCs) [58]. Moreover, the degree to which PBAE particles exert immunological activity is dependent on the polymer molecular weight, such that their stimulatory effect decreases as the polymer degrades by hydrolysis, and a macrophage activation pathway independent of Toll-like receptor (TLR) or NF-κB signaling pathways was found [59]. However, for some applications, such as genetic vaccines or gene therapies that require immune activation, these properties of PBAEs can be used as an advantage [60].…”

Section: Cationic Surface Charge-mentioning

confidence: 99%

Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

Karlsson

Rhodes

Green

et al. 2020

Expert Opinion on Drug Delivery

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Introduction: Gene delivery technologies are being developed for an increasing number of biomedical applications, with delivery vehicles including viruses and non-viral materials. Among biomaterials used for non-viral gene delivery, poly(beta-amino ester)s (PBAEs), a class of synthetic, biodegradable polymers, have risen as a leading gene delivery vehicle that has been used for multiple applications in vitro and in vivo.Areas covered: This review summarizes the key properties of PBAEs and their development, including a discussion of the advantages and disadvantages of PBAEs for gene delivery applications. The use of PBAEs to improve the properties of other drug delivery vehicles is also summarized. Expert opinion:PBAEs are designed to have multiple characteristics that are ideal for gene delivery, including their reversible positive charge, which promotes binding to nucleic acids as well as imparting high buffering capacity, and their rapid degradability under mild conditions. Simultaneously, some of their properties also lead to nanoparticle instability and low transfection efficiency in physiological environments. The ease with which PBAEs can be chemically modified

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“…Although this strategy has demonstrated promising results, the addition of a delivery vehicle increases overall vaccine complexity which is a significant hurdle for translation. Further, a number of recent investigations have revealed that many common particulate carriers exhibit some degree of intrinsic immunogenicity . This immunogenicity adds a confounding factor which complicates the understanding of the role of individual vaccine components.…”

Section: Nps and Mps Offer Attractive Features As Carriers Of Signalsmentioning

confidence: 99%

Engineering Immune Tolerance with Biomaterials

Gammon

Jewell

2019

Adv Healthcare Materials

Self Cite

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Autoimmune diseases, rejection of transplanted organs and grafts, chronic inflammatory diseases, and immune‐mediated rejection of biologic drugs impact a large number of people across the globe. New understanding of immune function is revealing exciting opportunities to help tackle these challenges by harnessing—or correcting—the specificity of immune function. However, realizing this potential requires precision control over the interaction between regulatory immune cues, antigens attacked during inflammation, and the tissues where these processes occur. Engineered materials—such as polymeric and lipid particles, scaffolds, and inorganic materials—offer powerful features that can help to selectively regulate immune function during disease without compromising healthy immune functions. This review highlights some of the exciting developments to leverage biomaterials as carriers, depots, scaffolds—and even as agents with intrinsic immunomodulatory features—to promote immunological tolerance.

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A poly(beta-amino ester) activates macrophages independent of NF-κB signaling

Cited by 29 publications

References 44 publications

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

Engineering Immune Tolerance with Biomaterials

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