Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers

Si, Yingnan; Chen, Kai; Ngo, Hanh Giai; Guan, Jia; Totoro, Angela; Zhou, Zhuoxin; Kim, Seulhee; Kim, Tae Hyun; Zhou, Lufang; Liu, Margaret

doi:10.3390/pharmaceutics14010146

Cited by 13 publications

(5 citation statements)

References 65 publications

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“…The biosimilar of Cetuximab, anti-EGFR mAb (Bio X Cell, Lebanon, NH), was tagged to the surface of Exo-AAV via mPEG-DSPE linker to generate the TNBC-targeting mAb-Exo-AAV. Following the procedure developed in our previous study (61,69,70), Exo-AAV was labeled with fluorescent dye Cy5.5 PE (only for IVIS imaging) and modified by mPEG-DSPE with a molar ratio of 1:10,000:6,000,000 (Exo-AAV:Cy5.5:mPEG-DSPE). The Exo-AAV-PEG-Cy5.5 was conjugated with anti-EGFR mAb via DSPE-PEG-NHS linker with a molar ratio of 1:2,680:13,000.…”

Section: Mab-exo-aav Construction and Titrationmentioning

confidence: 99%

An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment

Chen,

Ernst,

Kim

et al. 2024

Preprint

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Targeting cancer cell mitochondria holds great promise for cancer treatment, yet current strategies for specifically and effectively destroying cancer mitochondria in vivo are limited. Here, we introduce mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics technology designed to directly disrupt the inner mitochondrial membrane (IMM) potential and induce cancer cell death. We synthesize a blue light-gated channelrhodopsin (CoChR) in the IMM with a mitochondrial leading sequence and co-express a blue bioluminescence-emitting Nanoluciferase (NLuc) in the cytosol of the same cells. The mLumiOpto genes are selectively delivered to cancer cells in vivo by using two strategies: adeno-associated virus (AAV) carrying a cancer-specific promoter (cfos) or cancer-targeted monoclonal antibody-tagged exosome-associated AAV (mAb-Exo-AAV). Induction with ViviRen (an NLuc luciferin) elicits robust endogenous NLuc bioluminescence, which activates mitochondrial CoChR, triggering cancer cell IMM permeability disruption, IMM potential depolarization and subsequent cell death. Importantly, mLumiOpto demonstrates remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastomas (administrated with AAV) or triple-negative breast cancers (administrated with mAb-Exo-AAV) xenografted mouse models. These findings establish mLumiOpto as a novel and promising therapeutic strategy by targeting cancer cell mitochondria in vivo.

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Section: Mab-exo-aav Construction and Titrationmentioning

confidence: 99%

An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment

Chen,

Ernst,

Kim

et al. 2024

Preprint

Self Cite

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“…However, its efficacy is limited by innate and acquired chemoresistance, which may result in more side effects [ 218 , 219 ]. With the recent development of nanomedicines, targeted therapy has been primarily used to improve the efficacy of chemotherapy and reduce adverse effects [ 220 , 221 ]. Nanocarriers cannot easily penetrate micro-vessel walls in normal tissues because their endothelial gap is dense and structurally intact.…”

Section: Applications Of Lipid-hybrid Cell-derived Biomimetic Functio...mentioning

confidence: 99%

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors

Liu

Chen

et al. 2023

Materials Today Bio

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“…The addition of a PARP inhibitor with PD-1+ EVs further improves the treatment efficacy [152]. Moreover, EVs from HEK293F cells are also shown to target TNBC tumors when bioengineered to contain verrucarin A (Ver-A) followed by surface tagging with anti-EGFR/CD47 mAbs [153].…”

Section: Evs In Tnbc Immunotherapymentioning

confidence: 99%

Extracellular Vesicles in Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential

Das,

Paul,

Ghosh

et al. 2023

Cancers

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Triple–negative breast cancer (TNBC) is an aggressive subtype accounting for ~10–20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2–targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range of patients, and the emerging resistance further adds to the difficulties. Furthermore, TNBC exhibits a higher mutational burden and is acknowledged as the most immunogenic of all BC subtypes. Consequently, the application of immune checkpoint inhibition has been investigated in TNBC, yielding promising outcomes. Recent evidence identified extracellular vesicles (EVs) as an important contributor in the context of TNBC immunotherapy. In view of the extraordinary ability of EVs to transfer bioactive molecules, such as proteins, lipids, DNA, mRNAs, and small miRNAs, between the cells, EVs are considered a promising diagnostic biomarker and novel drug delivery system among the prospects for immunotherapy. The present review provides an in–depth understanding of how EVs influence TNBC progression, its immune regulation, and their contribution as a predictive biomarker for TNBC. The final part of the review focuses on the recent key advances in immunotherapeutic strategies for better understanding the complex interplay between EVs and the immune system in TNBC and further developing EV–based targeted immunotherapies.

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Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers

Cited by 13 publications

References 65 publications

An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment

An Innovative Mitochondrial-targeted Gene Therapy for Cancer Treatment

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors

Extracellular Vesicles in Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential

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