High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma

Kim, Gloria B.; Aragon‐Sanabria, Virginia; Randolph, Lauren N.; Jiang, Hali; Reynolds, Joshua; Webb, Becky; Madhankumar, A.; Lian, Xiaojun; Connor, James R.; Yang, Jian; Dong, Chuan

doi:10.1016/j.bioactmat.2020.04.011

Cited by 40 publications

(44 citation statements)

References 39 publications

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“…Immunotherapy aims to induce or expand the host's anticancer immune response, which can distinguish the subtle differences between cancerous cells and healthy cells. In recent years, great progress has been made in treating malignant tumors via activation of the host's immune system, targeted cellular therapeutics [ [8] , [9] , [10] , [11] , [12] ], immune checkpoint blockade [ [13] , [14] , [15] ], and therapeutic cancer vaccines [ [16] , [17] , [18] , [19] ].…”

Section: Introductionsmentioning

confidence: 99%

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

Fan

Liu

Xue

et al. 2021

Bioactive Materials

129

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Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors. As effective carriers, metal-organic frameworks (MOFs) have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity. Herein, we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF (MIL101-NH 2 ) as the core carrier; the MOF was dual-dressed with photoacoustic and fluorescent signal donors (indocyanine green, ICG) and immune adjuvants (cytosine-phosphate-guanine sequence, CpG) and named ICG-CpG@MOF. This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging (fluorescence, photoacoustic, photothermal and magnetic resonance imaging) of the tumor. Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation. ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment. Furthermore, the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system, which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects. This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.

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Section: Introductionsmentioning

confidence: 99%

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

Fan

Liu

Xue

et al. 2021

Bioactive Materials

129

View full text Add to dashboard Cite

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“…As shown in Fig. 8 A, RGDfC-Se@siSox2 significantly down-regulated the protein expression of ki67 (cell proliferation-related protein) compared to saline (control) and RGDfC-Se@siNC (negative control) groups because of the siSox2-silencing effect [ 48 ]. RGDfC-Se@siSox2 also inhibited the expression of the CD31 (a tumor angiogenesis-related protein) and up-regulated the expression of apoptosis-promoting proteins caspase-3 and phosphorylated p53, compared to saline and RGDfC-Se@siNC groups.…”

Section: Resultsmentioning

confidence: 99%

Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma

Xia

Tang

Chen

et al. 2021

Bioactive Materials

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RNA interference (RNAi) is one of the most promising methods for the treatment of malignant tumors. However, developing an efficient biocompatible delivery vector for small interfering RNA (siRNA) remains a challenging issue. This study aimed to prepare a non-viral tumor-targeted carrier, named RGDfC-modified functionalized selenium nanoparticles (RGDfC-SeNPs). RGDfC-SeNPs were used to selectively deliver siSox2 to HepG2 liver cancer cells and tissues for the treatment of hepatocellular carcinoma (HCC). In the current study, RGDfC-SeNPs were successfully synthesized and characterized. It was shown that RGDfC-SeNPs could effectively load siSox2 to prepare an antitumor prodrug RGDfC-Se@siSox2. RGDfC-Se@siSox2 exhibited selective uptake in HepG2 liver cancer cells and LO2 normal liver cells, indicating RGDfC-SeNPs could effectively deliver siSox2 to HepG2 liver cancer cells. RGDfC-Se@siSox2 entered HepG2 cells via clathrin-mediated endocytosis by firstly encircling the cytoplasm and then releasing siSox2 in the lysosomes. RGDfC-Se@siSox2 could effectively silence Sox2 and inhibit the proliferation, migration and invasion of HepG2 cells. RGDfC-Se@siSox2 induced HepG2 cells apoptosis most likely via overproduction of reactive oxygen species and disruption of the mitochondrial membrane potentials. Most importantly, RGDfC-Se@siSox2 significantly inhibited the tumor growth in HepG2 tumor-bearing mice without obvious toxic side effects. These studies indicated that RGDfC-SeNPs may be an ideal gene carrier for delivering siSox2 to HepG2 cells and that RGDfC-Se@siSox2 may be a novel and highly specific gene-targeted prodrug therapy for HCC.

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“…The results of the study showed the ability of LNPs to deliver mRNA from the CAR to primary T cells and generate functional CAR T cells that have the potential to induce cancer cell death [ 159 ]. Furthermore, another approach to reprogramming T cells is to use nanocarriers to deliver drugs, antibodies, and interleukins, as they can protect T cells from immunosuppression and activate CD8+ T cells [ 160 , 161 , 162 , 163 , 164 ].…”

Section: 3 T Cellsmentioning

confidence: 99%

Nanocarriers Used in Drug Delivery to Enhance Immune System in Cancer Therapy

et al. 2021

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Cancer, a group of diseases responsible for the second largest cause of global death, is considered one of the main public health problems today. Despite the advances, there are still difficulties in the development of more efficient cancer therapies and fewer adverse effects for the patients. In this context, nanobiotechnology, a materials science on a nanometric scale specified for biology, has been developing and acquiring prominence for the synthesis of nanocarriers that provide a wide surface area in relation to volume, better drug delivery, and a maximization of therapeutic efficiency. Among these carriers, the ones that stand out are those focused on the activation of the immune system. The literature demonstrates the importance of this system for anticancer therapy, given that the best treatment for this disease also activates the immune system to recognize, track, and destroy all remaining tumor cells.

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High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma

Cited by 40 publications

References 39 publications

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma

Nanocarriers Used in Drug Delivery to Enhance Immune System in Cancer Therapy

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