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Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical
Jiaxin Sui1,2,3,4,5, HanBin Qin2,3,4,5,6, Zile Zhang2,3,4,5,7
1Qingdao University Medical College, Qingdao University, Qingdao, Shandong Province, People's Republic of China.
Abstract:
Cancer remains a leading cause of global morbidity and mortality, yet conventional therapies, including surgery, radiotherapy, and chemotherapy, are often limited by invasiveness, systemic toxicity, and drug resistance. In this context, extracellular vesicles (EVs) have emerged as a promising cell-free nanotherapeutic platform. As endogenous nanocarriers, EVs enable precise, targeted delivery of diverse bioactive cargoes (eg, nucleic acids, chemotherapeutics, immunomodulators) to tumor tissues, thereby enhancing therapeutic efficacy while minimizing off-target effects, which is the key advantages for their application in tumor targeted therapy. This review systematically summarizes the characteristics of animal-derived and plant-derived EVs and highlights their translational applications in multiple cancers via immune activation, targeted delivery, tumor microenvironment remodeling, and anti-angiogenesis. We further introduce advanced bioengineering strategies for EV modification to optimize cargo loading, targeting specificity, and in vivo stability, particularly frontier innovations such as artificial intelligence-assisted design and microfluidic manufacturing that improve the precision, controllability, and scalability of engineered EVs. Compared to synthetic nanocarriers, EVs exhibit unique advantages, including excellent biocompatibility, low immunogenicity, and superior ability to cross biological barriers. However, the clinical application of EV-based therapies faces notable challenges, including EV heterogeneity, scalability of production, standardization of characterization methods, cargo loading efficiency, and long-term safety concerns. This review emphasizes the transformative potential of engineered EVs in advancing tumor targeted therapy and improving outcomes for patients with refractory or metastatic tumors.
Insights
Extracellular vesicles (EVs) offer a promising cell-free nanotherapeutic approach for cancer treatment, enabling targeted delivery of therapeutic agents to tumors. Bioengineering strategies and AI advancements are optimizing engineered EVs for improved cancer therapy, despite challenges in production and standardization.
Area of Science:
- Nanomedicine and Drug Delivery
- Cancer Therapeutics
- Biotechnology
Background:
- Conventional cancer therapies face limitations such as invasiveness, toxicity, and drug resistance.
- Extracellular vesicles (EVs) are emerging as a promising cell-free nanotherapeutic platform due to their natural targeting and cargo delivery capabilities.
- EVs offer advantages over synthetic nanocarriers, including biocompatibility, low immunogenicity, and ability to cross biological barriers.
Purpose of the Study:
- To systematically review the characteristics of animal- and plant-derived EVs for cancer therapy.
- To highlight the translational applications of EVs in oncology, including immune activation, targeted delivery, and tumor microenvironment remodeling.
- To introduce advanced bioengineering strategies for optimizing engineered EVs, including AI-assisted design and microfluidic manufacturing.
Main Methods:
- Systematic review of existing literature on EV characteristics and applications in cancer.
- Summary of bioengineering strategies for modifying EVs to enhance cargo loading, targeting, and stability.
- Discussion of frontier innovations like AI and microfluidics in EV production and design.
Main Results:
- Animal- and plant-derived EVs show potential in various cancer treatments through immune activation, targeted delivery, tumor microenvironment modulation, and anti-angiogenesis.
- Engineered EVs demonstrate improved precision, controllability, and scalability through advanced bioengineering techniques.
- EVs possess superior biocompatibility and targeting capabilities compared to synthetic nanocarriers.
Conclusions:
- Engineered EVs hold transformative potential for advancing tumor-targeted therapy, especially for refractory or metastatic cancers.
- Addressing challenges such as EV heterogeneity, production scalability, standardization, and safety is crucial for clinical translation.
- Further research and development in EV bioengineering are essential to fully realize their therapeutic promise in oncology.
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