دانلود مقاله وزیکول خارج سلولی باکتری به عنوان نانودارو

چکیده
مقدمه
مکانیسم بیوژنز وزیکول های خارج سلولی مشتق از باکتری های مختلف
درونی سازی BEV ها در سلول های میزبان
تعامل BEVs با سیستم ایمنی میزبان
پیشرفت های اخیر در نانوداروهای مبتنی بر BEVs
مزایای BEVs
نتیجه گیری و دیدگاه بیشتر
در دسترس بودن داده ها و مواد
اختصارات
مراجع

Abstract
Introduction
Biogenesis mechanism of diverse bacteria-derived extracellular vesicles
Internalisation of BEVs into host cells
Interaction of BEVs with the host immune system
Recent advances in BEVs-based nanopharmaceuticals
Advantages of BEVs
Conclusion and further perspective
Availability of data and materials
Abbreviations
References

چکیده
باکتری‌های وزیکول‌های خارج سلولی (BEVs)، که به عنوان نانوذرات دولایه‌ای احاطه‌شده با غشای لیپیدی مشخص می‌شوند که با محموله‌های مولکولی از سلول‌های مادر پر شده‌اند، نقش اساسی در رشد و پاتوژنز باکتری‌ها و همچنین تسهیل تعامل ضروری بین باکتری‌ها و سیستم‌های میزبان دارند. قابل ذکر است، BEVها با بهره مندی از عملکردهای بیولوژیکی منحصر به فرد خود، به عنوان نانوداروهای جدید برای پتانسیل های زیست پزشکی متنوع، نوید زیادی دارند و توجه قابل توجهی را هم از طرف صنعت و هم از دانشگاه ها به خود جلب می کنند. به طور معمول، BEV ها به دلیل قابلیت هدف گیری سلولی ذاتی، سهولت مهندسی محموله همه کاره و قابلیت نفوذ به موانع فیزیولوژیکی، به عنوان پلتفرم های تحویل دارو امیدوارکننده ارزیابی می شوند. علاوه بر این، با نسبت دادن به ایمنی ذاتی قابل توجه، BEVs قادر به تعامل با سیستم ایمنی میزبان برای تقویت ایمونوتراپی به عنوان نانوواکسن جدید در برابر طیف گسترده ای از بیماری ها هستند. در راستای این جهت‌های مهم، در این بررسی، ماهیت BEVها و نقش آن‌ها در فعال‌سازی پاسخ ایمنی میزبان را برای درک بهتر توسعه نانوداروهای مبتنی بر BEV روشن می‌کنیم. علاوه بر این، ما همچنین به طور سیستماتیک پیشرفت های اخیر در BEV ها را برای دستیابی به تحویل هدف مواد ژنتیکی، عوامل درمانی و مواد کاربردی خلاصه می کنیم. علاوه بر این، استراتژی‌های واکسیناسیون با استفاده از BEVs به دقت پوشش داده شده‌اند که پتانسیل درمانی انعطاف‌پذیر آن‌ها را در مبارزه با عفونت‌های باکتریایی، عفونت‌های ویروسی و سرطان نشان می‌دهد. در نهایت، موانع فعلی و چشم انداز بیشتر این نانوداروهای مبتنی بر BEV نیز ارائه خواهد شد.

Abstract

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals’ development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.

Introduction

Vesiculation is a crucial and fundamental process across all kinds of species to produce the extracellular vesicles that serve as essential mediators of basic physiological events [1]. These nanovesicles are filled with molecular patterns originated from parent cells, including metabolites, nucleic acids, proteins, and signaling molecules, to maintain cell growth and homeostasis [2, 3]. Biological regulation by extracellular vesicles is widespread across both prokaryotes and eukaryotes [4]. Notably, bacteria, as one of the major inhabitants in the human body, establish intricate relationships with host health and disease, wherein bacterial extracellular vesicles (BEVs) are indispensably involved in these processes [5, 6]. With the increasing and deep understanding of their biological function, BEVs are found to influence various cellular behaviors, including the transport of genetic information, phage infection, mediation of metabolism, as well as interaction between bacteria-bacteria and bacteria-host [7, 8].

Particularly, BEVs are characterized as nanosized nanoparticles, surrounded by lipid-bilayer membranes, ranging from 20 to 400 nm in diameter [7]. In account of the diversity of bacterial types and biogenesis mechanisms, the BEVs could carry versatile cargos inherited from mother cells, such as lipopolysaccharides (LPS), endotoxins, genetic information, cytosolic and membrane proteins [9]. By thanking the unique structure and intrinsic properties of BEVs, these naturally occurring nanovesicles attract the research interest to be developed as novel nanopharmaceuticals, prompting further exploration of their biomedical applications [10, 11]. Generally, BEVs are widely evaluated as biotherapeutics in different forms. Firstly, these nanovesicles with hollow structures could serve as novel drug delivery platforms, facilitating the transport of diverse bioactive molecules and therapeutic cargo to the recipient cells at the lesion site [12]. Thanks to the stability of naturally-occurring membrane structure, the BEVs-based drug delivery platform could carry the therapeutic genetic tools (e.g. siRNA, CRISPR-Cas9, etc.), protecting them from enzymatic degradation or hydrolysis in the complex physiological environment [13, 14]. Besides, benefiting from the ease of modification, BEVs-based drug delivery platforms could efficiently load the small molecular therapeutics [14], or directly produce the synthetic cargo (e.g. antigens, enzymes, therapeutic proteins, etc.) on the BEVs by editing the desired gene in parent bacteria. The BEVs-based drug carriers are also featured in their capability for targeting delivery toward the disease area to enhance drug accumulation and availability [15]. Moreover, the BEVs drug delivery platform can integrate with functional materials, to facilitate combinational therapy (e.g. photodynamic therapy, photothermal therapy, etc.) and maximize the synergistic therapeutic efficiency [16].

Conclusion and further perspective

In this review, we comprehensively summarize the development of BEV-based nanopharmaceuticals to facilitate disparate biomedical applications in recent years. Amongst the unique advantages and functions of BEVs, we demonstrated the tremendous potential of applying these naturally occurring nanovesicles to establish a myriad of innovative therapeutic strategies for new-generation pharmaceuticals evolution, especially in the versatile bioactive cargo delivery and powerful vaccination approaches.

Taking the unique merits of nanovesicles, the structural stability, ease of cargo loading, promising penetration across physiological barriers, and specific targeting capabilities endow the BEVs application to be beneficial in delivery for a wide range of therapeutics. Particularly, the naturally occurring membrane structure of BEVs enables targeting delivery of therapeutic genetic tools (e.g., siRNA, DNA, CRISPR-Cas9, etc.) in the physiological, preserving stability and bioactivity, thus enhancing gene therapy. Leveraging the ease of genetic modification in parent bacteria, protein cargo, such as enzymes and antigens, can also be directly expressed within BEVs, optimizing loading efficiency compared to conventional delivery platforms. Furthermore, advancements in nanotechnology and material science have witnessed the integration of functional materials with BEV delivery platforms to achieve combinational therapy, thereby further improving the synergistic therapeutic efficacy.