Rationalizing the Use of Functionalized Poly-Lactic-Co-Glycolic Acid Nanoparticles for Dendritic Cell-Based Targeted Anticancer Therapy

Kokate, Rutika; Chaudhary, Pankaj; Sun, Xiangle; Thamake, Sanjay; Maji, Sayantan; Chib, Rahul; Vishwanatha, Jamboor K.; Jones, Harlan P.

doi:10.2217/nnm.15.213

Cited by 39 publications

(26 citation statements)

References 35 publications

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“…AM1 (400 μM) was dissolved in 980 μl HEPES (25 mM, pH vation, including greater infiltration by inflammatory DCs than myeloid suppressor cells and CD4 + and CD8 + T cell infiltration. Furthermore, in contrast to passive DC-targeting strategies (7,(44)(45)(46), a single administration of OVA-Clec9A-TNE inhibited the growth of and enhanced survival with the relatively immunogenic PyMT-OVA and AT3-OVA breast cancer models. After vaccine administration, the burst of IFN-α provoked systemic activation of CD8 + and CD8 -DCs.…”

Section: Methodsmentioning

confidence: 95%

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Zeng

Middelberg

Gemiarto

et al. 2018

Journal of Clinical Investigation

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could be achieved, the immunogenicity of TNE-encapsulated antigen was not explored. Here we show unexpectedly, given the lack of DC activation by anti-Clec9A-antigen conjugates, that in the absence of adjuvant, cross-presenting DCs targeted with antigenClec9A-TNE stimulate DC activation, antigen-specific CTLs, and highly effective tumor-specific immunity, dependent on the presence of CD4 helper epitopes and CD40 signaling.

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Section: Methodsmentioning

confidence: 95%

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Zeng

Middelberg

Gemiarto

et al. 2018

Journal of Clinical Investigation

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“…Besides DEX and starch also other carbohydrates like chitosan [ 30 ] were reported to trigger complement activation, which is of considerable importance given the ongoing interest in chitosan-based and -coated NC for biomedical applications [ 31 ]. Aside from carbohydrates also other surface properties may trigger complement activation as reported for positively charged poly(lactic-co-glycolic) acid (PLGA) based NC [ 32 ], another type of NC frequently used in preclinical [ 33 ] and clinical [ 34 ] studies. Therefore, in vivo complement opsonization of NC may contribute to their biodistribution in numerous cases.…”

Section: Discussionmentioning

confidence: 99%

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Bednarczyk

Medina‐Montano

Fittler

et al. 2021

IJMS

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The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.

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“…A similar study constructed a PLGA-based nanoparticle encapsulating CpG ODN-coated tumor antigen. This nanomedicine significantly enhances both maturation and activation of DCs and inhibits tumor growth and angiogenesis through induction of potent CTL responses in 4T1 breast tumorbearing mice [73]. Besides tumor peptides, delivery of tumor-associated mRNAs also exhibits a promising enhancement in immune system response.…”

Section: Delivery Of Tumor Antigens Through Nanoparticlesmentioning

confidence: 99%

Emerging nanomedicines for effective breast cancer immunotherapy

2020

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Breast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

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Rationalizing the Use of Functionalized Poly-Lactic-Co-Glycolic Acid Nanoparticles for Dendritic Cell-Based Targeted Anticancer Therapy

Abstract: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

Cited by 39 publications

References 35 publications

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Emerging nanomedicines for effective breast cancer immunotherapy

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