Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

Korang-Yeboah, Maxwell; Patel, Divya; Morton, Derrick J.; Sharma, Pankaj; Gorantla, Yamini; Joshi, Jugal; Nagappan, Perri; Pallaniappan, Ravi; Chaudhary, Jaideep

doi:10.18632/oncotarget.10953

Cited by 9 publications

(7 citation statements)

References 43 publications

(81 reference statements)

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“…Accordingly, delivery of Id4 encapsulated in biodegradable polycaprolactone/maltodextrin nanoparticles leads to increased apoptosis, decreased proliferation and colony formation. In vivo the Id4-nanoparticle approach has been shown to be more efficient than the administration of docetaxel in reducing the tumor volume [ 332 ].…”

Section: The Id Proteins As Therapeutic Targetsmentioning

confidence: 99%

The Id-protein family in developmental and cancer-associated pathways

2017

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Inhibitors of DNA binding and cell differentiation (Id) proteins are members of the large family of the helix-loop-helix (HLH) transcription factors, but they lack any DNA-binding motif. During development, the Id proteins play a key role in the regulation of cell-cycle progression and cell differentiation by modulating different cell-cycle regulators both by direct and indirect mechanisms. Several Id-protein interacting partners have been identified thus far, which belong to structurally and functionally unrelated families, including, among others, the class I and II bHLH transcription factors, the retinoblastoma protein and related pocket proteins, the paired-box transcription factors, and the S5a subunit of the 26 S proteasome. Although the HLH domain of the Id proteins is involved in most of their protein-protein interaction events, additional motifs located in their N-terminal and C-terminal regions are required for the recognition of diverse protein partners. The ability of the Id proteins to interact with structurally different proteins is likely to arise from their conformational flexibility: indeed, these proteins contain intrinsically disordered regions that, in the case of the HLH region, undergo folding upon self- or heteroassociation. Besides their crucial role for cell-fate determination and cell-cycle progression during development, other important cellular events have been related to the Id-protein expression in a number of pathologies. Dysregulated Id-protein expression has been associated with tumor growth, vascularization, invasiveness, metastasis, chemoresistance and stemness, as well as with various developmental defects and diseases. Herein we provide an overview on the structural properties, mode of action, biological function and therapeutic potential of these regulatory proteins.

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Section: The Id Proteins As Therapeutic Targetsmentioning

confidence: 99%

The Id-protein family in developmental and cancer-associated pathways

2017

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“…Different human malignancies have been detected for ID expression levels ( 5 ). For instance, it has been reported and agreed that increased levels of IDs were associated with malignant grade and a poor prognosis in various types of carcinoma ( 6 – 9 ). It has been revealed that increasing ID1 mRNA expression was observed in subtypes of human breast tumors and that this acted as a driver in BC metastasis ( 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

Prognostic values of the inhibitor of DNA‑binding family members in breast cancer

Zhou

Zeng

et al. 2018

Oncol Rep

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The inhibitor of DNA-binding (ID) proteins are dominant-negative modulators of transcription factors with basic helix-loop-helix (bHLH) structures, which control a variety of genes in cell cycle regulation. An increasing volume of evidence has demonstrated that the deregulated expression of IDs in several types of malignancy, including breast carcinoma, has been proven to serve crucial regulatory functions in tumorigenesis and the development of breast cancer (BC). The present study evaluated the prognostic values of the ID family members by investigating a set of publicly accessible databases, including Oncomine, bc-GenExMiner, Kaplan-Meier plotter and the Human Protein Atlas. The results demonstrated that mRNA levels of distinct IDs exhibited diverse profiles between BC and normal counterparts. The mRNA expression level of ID2 was significantly higher in breast cancer than normal tissues, while the mRNA expression levels of ID1, ID3 and ID4 were significantly lower in breast cancer tissues than in normal tissues. Furthermore, higher mRNA expression levels of ID1 and ID4 were associated with subgroups with lower pathological grades and fewer lymph node metastases. Survival analysis revealed that elevated mRNA levels of ID1 and ID4 predicted an improved survival in all patients with BC. Increased ID1 mRNA levels were associated with higher relapse-free survival rates in all patients with BC, particularly in those with ER positive and Luminal A subtype tumors. Increased ID4 mRNA expression predicted longer survival times in all patients with BC, particularly in those with hormone receptor-positive tumors or those treated with endocrine therapy. These results indicated that IDs are essential prognostic indicators in BC. Future studies on the effect of IDs on the pathogenesis and development of BC are warranted.

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“…An amine-terminated generation 5 polyamidoamine dendrimer was conjugated with guanidinobenzoic acid (GBA) for the protein vehicle [ 32 ]. Biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was used to deliver proteins into LNCaP cells [ 33 ]. The high efficiency of intracellular protein delivery can be safely used in cell differentiation and reprogramming in regenerative medicine and the differentiation therapy of cancers.…”

Section: Discussionmentioning

confidence: 99%

Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles

Chou

Hsia

et al. 2018

Materials

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Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.

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Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

Cited by 9 publications

References 43 publications

The Id-protein family in developmental and cancer-associated pathways

The Id-protein family in developmental and cancer-associated pathways

Prognostic values of the inhibitor of DNA‑binding family members in breast cancer

Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles

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