Intracellular delivery of peptide cargos using polyhydroxybutyrate based biodegradable nanoparticles: Studies on antitumor efficacy of BCL-2 converting peptide, NuBCP-9

Kapoor, Sanjiv; Gupta, Dablu Lal; Kumar, Manoj; Sharma, Sapna; Gupta, Amit; Misro, M. M.; Singh, Harpal

doi:10.1016/j.ijpharm.2016.07.077

Cited by 28 publications

(12 citation statements)

References 32 publications

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“…Agents that can bind directly to Nur77 to promote Nur77 translocation and interaction with Bcl-2 are unique in that they can simultaneously target both Nur77 and Bcl-2. The reported Nur77-derived peptide with 9 amino acids (NuBCP-9) and its enantiomer as Bcl-2-converting peptides has demonstrated such a potential (12,44,45). In this regard, our identification of small molecules that can directly bind Nur77 to activate the Nur77-Bcl-2 apoptotic pathway is significant and BI1071 represents the first lead of this class of small molecules, which warrants further evaluation.…”

Section: Discussionmentioning

confidence: 98%

BI1071, a Novel Nur77 Modulator, Induces Apoptosis of Cancer Cells by Activating the Nur77-Bcl-2 Apoptotic Pathway

Chen

Cao

et al. 2019

Molecular Cancer Therapeutics

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Nur77 (also called TR3 or NGFI-B), an orphan member of the nuclear receptor superfamily, induces apoptosis by translocating to mitochondria where it interacts with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic molecule. Nur77 posttranslational modification such as phosphorylation has been shown to induce Nur77 translocation from the nucleus to mitochondria. However, small molecules that can bind directly to Nur77 to trigger its mitochondrial localization and Bcl-2 interaction remain to be explored. Here, we report our identification and characterization of DIM-C-pPhCF 3 þ MeSO 3 À (BI1071), an oxidized product derived from indole-3-carbinol metabolite, as a modulator of the Nur77-Bcl-2 apoptotic pathway. BI1071 binds Nur77 with high affinity, promotes Nur77 mitochondrial targeting and interaction with Bcl-2, and effectively induces apoptosis of cancer cells in a Nur77-and Bcl-2-dependent manner. Studies with animal model showed that BI1071 potently inhibited the growth of tumor cells in animals through its induction of apoptosis. Our results identify BI1071 as a novel Nur77binding modulator of the Nur77-Bcl-2 apoptotic pathway, which may serve as a promising lead for treating cancers with overexpression of Bcl-2.

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Section: Discussionmentioning

confidence: 98%

BI1071, a Novel Nur77 Modulator, Induces Apoptosis of Cancer Cells by Activating the Nur77-Bcl-2 Apoptotic Pathway

Chen

Cao

et al. 2019

Molecular Cancer Therapeutics

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“…NuBCP-9, a nine AA Nur77-derived peptide, which induced a Bcl-2 conformational change, converted the protein from a cyto-protector to a cytocide. As a result, NuBCP-9 demonstrated potent anticancer activity while being harmless to normal cells …”

Section: Peptide Therapeutics In Cancer Therapymentioning

confidence: 99%

“…As a result, NuBCP-9 demonstrated potent anticancer activity while being harmless to normal cells. 43 In addition to these three major intracellular pathways, nonmembranolytic ACPs can target alternative pathways. For example, peptides that increase the half-life of p53 tumor suppressor protein can reduce the viability of cancer cell lines and of tumors in vivo.…”

Section: Therapeutic Anticancer Peptidesmentioning

confidence: 99%

Design of Polymeric Carriers for Intracellular Peptide Delivery in Oncology Applications

Sylvestre

Prossnitz

et al. 2021

Chem. Rev.

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In recent decades, peptides, which can possess high potency, excellent selectivity, and low toxicity, have emerged as promising therapeutics for cancer applications. Combined with an improved understanding of tumor biology and immuno-oncology, peptides have demonstrated robust antitumor efficacy in preclinical tumor models. However, the translation of peptides with intracellular targets into clinical therapies has been severely hindered by limitations in their intrinsic structure, such as low systemic stability, rapid clearance, and poor membrane permeability, that impede intracellular delivery. In this Review, we summarize recent advances in polymer-mediated intracellular delivery of peptides for cancer therapy, including both therapeutic peptides and peptide antigens. We highlight strategies to engineer polymeric materials to increase peptide delivery efficiency, especially cytosolic delivery, which plays a crucial role in potentiating peptide-based therapies. Finally, we discuss future opportunities for peptides in cancer treatment, with an emphasis on the design of polymer nanocarriers for optimized peptide delivery.

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“…) . Kapoor et al employed PHB–PEG nanoparticles to encapsulate the NuBCP‐9 peptide (FSRSLHSLL) which targeted Bcl‐2 anti‐apoptotic activity in cancer cells. PHB with a molecular weight of 72 000 g mol −1 was coupled with PEG of 4000 g mol −1 via Steglich esterification to obtain nanoparticles with encapsulated drug with an average diameter of 126 nm with loading efficiency of 61%.…”

Section: Phas In Biomedical Applicationsmentioning

confidence: 99%

Polyhydroxyalkanoate-based drug delivery systems

2016

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Microbial polyhydroxyalkanoates (PHAs) have been a subject of significant research interest in the past few decades. The recent development of novel functionalized PHAs has opened up new possibilities to combine the good biocompatibility of PHA-based drug delivery systems to, for example, improve drug loading and release properties, targeting or imaging functionalities. This mini-review presents some recent scientific developments in the preparation of functionalized PHAs, PHA-drug and PHA-protein conjugates, multifunctional PHA nanoparticles and micelles as well as biosynthetic PHA particles for drug delivery. These developments in combination with the generally excellent biocompatibility of PHA materials are expected to further expand the interest in PHA materials for drug delivery and other therapeutic applications.

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Intracellular delivery of peptide cargos using polyhydroxybutyrate based biodegradable nanoparticles: Studies on antitumor efficacy of BCL-2 converting peptide, NuBCP-9

Cited by 28 publications

References 32 publications

BI1071, a Novel Nur77 Modulator, Induces Apoptosis of Cancer Cells by Activating the Nur77-Bcl-2 Apoptotic Pathway

BI1071, a Novel Nur77 Modulator, Induces Apoptosis of Cancer Cells by Activating the Nur77-Bcl-2 Apoptotic Pathway

Design of Polymeric Carriers for Intracellular Peptide Delivery in Oncology Applications

Polyhydroxyalkanoate-based drug delivery systems

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