Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs

Jeon, In Seon; Yoo, Jae Do; Gurung, Smriti; Kim, Minseong; Lee, Chanju; Park, Eun Jung; Park, Rang-Woon; Lee, Byungheon; Kim, Soyoun

doi:10.1016/j.biomaterials.2021.120685

Cited by 32 publications

(43 citation statements)

References 57 publications

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“…This novel formulation showed superior activity compared to free DOX in reducing HCC tumor growth and metastases in preclinical models [48,89]. In another report, the PD-L1 binding peptide 1 (PD-L1pep1, CLQKTPKQC) was introduced into ferritin's sequence to generate an FN targeted to PD-L1 [34]. Another well-studied tumor-targeting ligand is the tLyp-1 peptide, which binds the receptor Neuropilin 1 expressed in the stroma of many types of tumors [90].…”

Section: Production and Modifications Of Fnmentioning

confidence: 99%

“…ICIs currently used in the clinical setting are monoclonal antibodies (mAbs) that are able to block the activity of the programmed cell death protein 1 (PD-1)/PD-L1 interaction or cytotoxic T-lymphocyte antigen-4 expressed by T cells. Recently, a DOX-loaded engineered FN displaying the PD-L1 binding peptide (PpNF) was developed by Seon and colleagues [34]. Interestingly, this novel nanoformulation was able to achieve enhanced tumor-growth reduction in the colon carcinoma CT26 xenograft model, as compared to anti-PD-L1 mAb and free DOX (Figure 5).…”

Section: Fn-based Nps For Immunomodulation and Immunotherapymentioning

confidence: 99%

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Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable characteristics of FNs is their intrinsic targeting efficiency toward the Transferrin Receptor 1, which is overexpressed in many tumors. Furthermore, genetic manipulation can be employed to introduce novel variants that are able to improve the loading capacity, targeting capabilities and bio-availability of this versatile drug delivery system. In this review, we discuss the main characteristics of FN and the most recent applications of this promising nanotechnology in the field of oncology with a particular emphasis on the imaging and treatment of solid tumors.

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Section: Production and Modifications Of Fnmentioning

confidence: 99%

Section: Fn-based Nps For Immunomodulation and Immunotherapymentioning

confidence: 99%

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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“…However, not all combination immunotherapy is safe. A PpNF (Dox) nanocage developed by the SoyounKim group decreased the weight of tumor-bearing mice in combination immunotherapy [52], which might be attributed to the off-target toxicity of Dox as it was effectively delivered to mice bodies by the nanocage. In view of this issue, we used a Bcl9 peptide in co-immunotherapy with intrinsic properties as we described.…”

Section: Discussionmentioning

confidence: 99%

Turning a Targeting β-Catenin/Bcl9 Peptide Inhibitor into a GdOF@Au Core/Shell Nanoflower for Enhancing Immune Response to Cancer Therapy in Combination with Immune Checkpoint Inhibitors

You

Zhang

et al. 2022

Pharmaceutics

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Combination administration is becoming a popular strategy in current cancer immunotherapy to enhance tumor response to ICIs. Recently, a peptide drug, a protein–protein interaction inhibitor (PPI), that disrupts the β-catenin/Bcl9 interaction in the tumoral Wnt/β-catenin pathway has become a promising candidate drug for immune enhancement and tumor growth inhibition. However, the peptide usually suffers from poor cell membrane permeability and proteolytic degradation, limiting its adequate accumulation in tumors and ultimately leading to side effects. Herein, a gadolinium–gold-based core/shell nanostructure drug delivery system was established, where Bcl9 was incorporated into a gadolinium–gold core–shell nanostructure and formed GdOFBAu via mercaptogenic self-assembly. After construction, GdOFBAu, when combined with anti-PD1 antibodies, could effectively inhibit tumor growth and enhance the response to immune therapy in MC38 tumor-bearing mice; it not only induced the apoptosis of cancer cells, but also promoted the tumor infiltration of Teff cells (CD8+) and decreased Treg cells (CD25+). More importantly, GdOFBAu maintained good biosafety and biocompatibility during treatment. Taken together, this study may offer a promising opportunity for sensitizing cancer immunotherapy via metal–peptide self-assembling nanostructured material with high effectiveness and safety.

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“…It is also a key marker of T-cell activation and proliferation. 4,6,39,44 In this study, total protein concentrations in isolated tumors were detected by the BCA protein assay kit, and subsequently, the levels of cytokine IFN-γ were determined by ELISA (Figure 5G). Compared with the saline group, the IFN-γ level in the siPD-L1@PM/DOX@LPs group increased significantly, reaching 0.50 ± 0.05 pg/μg (p < 0.001).…”

Section: 7mentioning

confidence: 95%

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

Yao

Wang

et al. 2022

ACS Appl. Mater. Interfaces

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Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.

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Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs

Cited by 32 publications

References 57 publications

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Turning a Targeting β-Catenin/Bcl9 Peptide Inhibitor into a GdOF@Au Core/Shell Nanoflower for Enhancing Immune Response to Cancer Therapy in Combination with Immune Checkpoint Inhibitors

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

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