Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies

Theranostics, Journal Year: 2022, Volume and Issue: 12(14), P. 6422 - 6436

Published: Jan. 1, 2022

Rationale: Messenger RNA (mRNA) vaccine outperforms other kinds of cancer immunotherapy due to its high response rates, easy preparation, and wide applicability, which is considered as one the most promising forms next-generation therapies.However, inherent instability insufficient protein expression duration mRNA limit efficacy widespread application vaccine.Methods: Here, we first tested possibility a novel circular (circRNA) platform for compare with linear RNA.Then, developed lipid nanoparticle (LNP) system circRNA delivery in vitro vivo.Next, innate adaptive immune circRNA-LNP complex was evaluated vivo.The anti-tumor further confirmed three tumor models.Finally, combination therapy adoptive cell transfer investigated late-stage model. Results:We successfully increased stability by circularizing molecules form highly stable exhibited durable ability.By encapsulating antigen-coding LNP enabling vivo expression, established platform, capable triggering robust activation showed superior multiple mouse models.Conclusions: Overall, our provides prospect development vaccines range hard-to-treat malignancies.

Language: Английский

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Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3778 - 3778

Published: March 29, 2022

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe the USA recent decades. Among different subtypes cancers, hepatocellular carcinoma (HCC) most commonly diagnosed cancer. Besides advances diagnosis promising results pre-clinical studies, HCC remains a highly lethal disease. In many cases, an effect chronic inflammation, which leads to formation complex tumor microenvironment (TME) composed immune stromal cells. TME patients challenge for therapies, as it involved metastasis development resistance. However, given that intricate system cells interacting cells, new immune-based therapies are being developed target HCC. Therefore, understanding complexity will provide possibilities design novel more effective immunotherapeutics combinatorial overcome resistance treatment. this review, we describe role inflammation during progression by focusing on TME. We also therapeutic possible treatment options.

Language: Английский

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Peptide–drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 498 - 516

Published: Aug. 3, 2022

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug (ADCs), with core benefits enhanced cellular permeability and improved selectivity. Two drugs now approved for market by US Food Drug Administration (FDA), in last two years, pharmaceutical companies have been developing PDCs as therapeutic candidates cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, so on. The significant, but poor stability, low bioactivity, long research development time, slow clinical process agents PDC, how can we design more effectively what is future direction PDCs? This review summarises components functions therapeutic, from target screening PDC improvement strategies to applications improve permeability, targeting, stability various PDCs. holds great promise PDCs, such bicyclic peptide‒toxin coupling or supramolecular nanostructures peptide-conjugated drugs. mode delivery determined according current trials summarised. way shown development.

Language: Английский

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Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics

ACS Nano, Journal Year: 2023, Volume and Issue: 17(23), P. 23223 - 23261

Published: Dec. 2, 2023

Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological enzymes, external lasers ultrasound, etc., by changing their hydrophobicity/hydrophilicity, degradability, ionizability, thus have been widely used in biomedical applications. Due the characteristics of tumor microenvironment (TME), stimuli-responsive that cater specifically TME extensively prepare smart nanovehicles for targeted delivery therapeutic diagnostic agents tissues. Compared conventional drug nanosystems, TME-responsive nanosystems many advantages, high sensitivity, broad applicability among different tumors, functional versatility, improved biosafety. In recent years, a great deal research has devoted engineering efficient polymeric significant improvement made both cancer diagnosis therapy. this review, we summarize some advances involving use polymer nanocarriers delivery, imaging, therapy, theranostics. Various chemical stimuli will be described context nanosystems. Accordingly, groups responsible responsiveness strategies incorporate these into discussed detail. With on topic expending at fast pace, innovative concepts, sequential cascade release, NIR-II multifunctional formulations, emerged popular enhanced performance, which also included here with up-to-date illustrations. We hope review offer valuable insights selection optimization help accelerate future applications treatment.

Language: Английский

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Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 4, 2021

Abstract Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, distant metastases among patients with advanced account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, factors, which play significant role in supporting behavior cells. complex dynamic interactions secreted cytokines, chemokines, their receptors mediate chronic inflammation immunosuppressive TME favoring progression, metastasis, decreased response therapy. molecular changes are used as biological markers diagnosis, prognosis, treatment patients. This review highlighted novel insights into understanding functional impact deregulated cytokines chemokines imparting EC, stressing nature therapeutic consequences cytokine-chemokine network. We also discuss oncogenic potential contributing Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, development. In addition, it discusses wide range intracellular signaling pathways that occur TME. Overall, this relatively unexplored field could provide crucial immunology encourage effective application modulatory therapy EC.

Language: Английский

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