Multifunctional nanoparticles for cancer immunotherapy

Saleh, Tayebeh; Shojaosadati, Seyed Abbas

doi:10.1080/21645515.2016.1147635

Cited by 35 publications

(36 citation statements)

References 88 publications

(131 reference statements)

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“…The physicochemical characteristics of the nanoparticles, such as size, shape, surface charge, and surface functionalization, are crucial parameters in designing DDS for cancer immunotherapy [36]. The delivery mechanism of nanoparticles depends greatly on enhanced permeation and retention effects.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

et al. 2017

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Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients. Early clinical substantiation lends weight to the claim that cancer immunotherapies, which are adaptive and enduring treatment methods, generate much more sustained and robust anticancer effects when they are effectively formulated in nanoparticles or scaffolds than when they are administered as free drugs. Engineering cancer immunotherapies using nanomaterials is, therefore, a very promising area worthy of further consideration and investigation. This review focuses on the recent advances in cancer immunoengineering using nanoparticles for enhancing the therapeutic efficacy of a diverse range of immunotherapies. The delivery of immunostimulatory agents to antitumor immune cells, such as dendritic or antigen presenting cells, may be a far more efficient tactic to eradicate tumors than delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In addition to its immense therapeutic potential, immunoengineering using nanoparticles also provides a valuable tool for unearthing and understanding the basics of tumor biology. Recent research using nanoparticles for cancer immunotherapy has demonstrated the advantage of physicochemical manipulation in improving the delivery of immunostimulatory agents. In vivo studies have tested a range of particle sizes, mostly less than 300 nm, and particles with both positive and negative zeta potentials for various applications. Material composition and surface modifications have been shown to contribute significantly in selective targeting, efficient delivery and active stimulation of immune system targets. Thus, these investigations, including a wide array of nanoparticles for cancer immunotherapy, substantiate the employment of nanocarriers for efficacious cancer immunotherapies.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

et al. 2017

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“…Signal transducer and activator of transcription (STAT3) signaling is an important pathway that can mediate immune suppression at the tumor microenvironment. The induction of the transcriptional activity of STAT3 by the tumor cells mediates tumor growth by promoting angiogenesis and hypoxia, accomplished by an increased expression of matrix metalloproteinases and secretion of suppressive cytokines (e.g., IL‐10, IL‐6, and TGF‐β), while reducing the production of proinflammatory cytokines (e.g., IL‐12, IFN‐γ, and TNF) . Therefore, silencing STAT3 in DCs is another useful approach in cancer immunotherapy.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…Besides the inherent adjuvancy of some nanosystems, the use of stimuli‐responsive materials to deliver antigens and/or immunostimulatory molecules can also amplify the immune activation ( Figure ) …”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…Generally, nonviral delivery systems are internalized via the endocytosis pathway, in which the NPs become entrapped in endosomes, and ultimately end up in the lysosome, where they can suffer an active enzymatic degradation processes . Thus, antigens loaded into NPs are entrapped in the endocytic compartments, and further intracellular transport toward the cytoplasm is prevented.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

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Immunostimulation and Immunosuppression: Nanotechnology on the Brink

et al. 2018

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Immunotherapy is revolutionizing current therapies in cancer and in autoimmune diseases, showing impressive results in clinical trials. Recently, the development of innovative nano‐biomaterials has been focusing on the interactions between such materials and the immune system, both in the adaptive and innate branches. Biomaterials can display immunostimulative, neutral, or immunosuppressive interactions. Nanoparticles displaying immunostimulative potential are employed in the formulation of cancer vaccines, while immunosuppressive materials are being researched for the development of vaccines able to induce tolerance in autoimmune diseases. Here, the properties influencing the immunomodulation effect of nanomaterials are analyzed, followed by a detailed review of the recent applications of nanomaterials for the delivery of antigens, adjuvants, chemotherapeutics, and immunomodulatory drugs.

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“…21,22 Successful fabrication and implementation of such systems requires consideration of variables such as material toxicity, particle size, particle shape, surface charge, and stiffness or rigidity. 23,24 For efficient delivery, size is a major parameter. Small particles in the 10–50 nm size range selectively accumulate in the lymphatic system and lymph nodes, where DCs are present in large numbers, whereas larger particles are mostly taken up by macrophages.…”

Section: Introductionmentioning

confidence: 99%

Toward Personalized Peptide-Based Cancer Nanovaccines: A Facile and Versatile Synthetic Approach

et al. 2017

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Personalized cancer vaccines (PCVs) are receiving attention as an avenue for cancer immunotherapy. PCVs employ immunogenic peptide epitopes capable of stimulating the immune system to destroy cancer cells with great specificity. Challenges associated with effective delivery of these peptides include poor solubility of hydrophobic sequences, rapid clearance, and poor immunogenicity, among others. The incorporation of peptides into nanoparticles has the potential to overcome these challenges, but the broad range of functionalities found in amino acids presents a challenge to conjugation due to possible interferences and lack of reaction specificity. Herein, a facile and versatile approach to generating nanosized PCVs under mild nonstringent conditions is reported. Following a simple two-step semibatch synthetic approach, amphiphilic hyperbranched polymer–peptide conjugates were prepared by the conjugation of melanoma antigen peptides, either TRP2 (hydrophobic) or MUT30 (hydrophilic), to an alkyne functionalized core via strain-promoted azide–alkyne click chemistry. Self-assembly of the amphiphiles gave spherical nanovaccines (by transmission electron microscopy) with sizes in the range of 10–30 nm (by dynamic light scattering). Fluorescently labeled nanovaccines were prepared to investigate the cellular uptake by antigen presenting cells (dendritic cells), and uptake was confirmed by flow cytometry and microscopy. The TRP2 nanovaccine was taken up the most followed by MUT30 nanoparticles and, finally, nanoparticles without peptide. The nanovaccines showed good biocompatibility against B16–F10 cells, yet the TRP2 peptide showed signs of toxicity, possibly due to its hydrophobicity. A test for immunogenicity revealed that the nanovaccines were poorly immunogenic, implying the need for an adjuvant when administered in vivo. Treatment of mice with melanoma tumors showed that in combination with adjuvant, CpG, groups with the peptide nanovaccines slowed tumor growth and improved survival (up to 24 days, TRP2) compared to the untreated group (14 days).

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Multifunctional nanoparticles for cancer immunotherapy

Cited by 35 publications

References 88 publications

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

Immunostimulation and Immunosuppression: Nanotechnology on the Brink

Toward Personalized Peptide-Based Cancer Nanovaccines: A Facile and Versatile Synthetic Approach

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