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The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, delving into their unique characteristics and mechanisms in detail. Special attention is given to their ability to strategically evade endosomal entrapment, thereby enhancing therapeutic efficacy. The manuscript thoroughly examines assays crucial for understanding endosomal escape and cellular uptake dynamics. By analyzing various assessment methods, we offer nuanced insights into these investigative approaches' multifaceted aspects. We meticulously analyze the use of smart nanocarriers, exploring diverse mechanisms such as pore formation, proton sponge effects, membrane destabilization, photochemical disruption, and the strategic use of endosomal escape agents. Each mechanism's effectiveness and potential application in mitigating endosomal entrapment are scrutinized. This paper provides a critical overview of the current landscape, emphasizing the need for advanced delivery systems to navigate the complexities of cellular uptake. Importantly, it underscores the transformative role of smart nanomaterials in revolutionizing cellular delivery strategies, leading to a paradigm shift towards improved therapeutic outcomes.
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Endossomos , Lisossomos , Lisossomos/metabolismo , Humanos , Endossomos/metabolismo , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Nanoestruturas/química , Animais , Nanopartículas/químicaRESUMO
Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.
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Materiais Biomiméticos , Regeneração Óssea , Microesferas , Nanofibras , Engenharia Tecidual , Humanos , Regeneração Óssea/efeitos dos fármacos , Nanofibras/química , Materiais Biomiméticos/química , Osteogênese/efeitos dos fármacos , Animais , Tamanho da Partícula , Osso e Ossos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Alicerces Teciduais/químicaRESUMO
The application of nanotechnology has significantly advanced the development of novel platforms that enhance disease treatment and diagnosis. A key innovation in this field is the creation of antitoxin nanoparticles (ATNs), designed to address toxin exposure. These precision-engineered nanosystems have unique physicochemical properties and selective binding capabilities, allowing them to effectively capture and neutralize toxins from various biological, chemical, and environmental sources. In this review, we thoroughly examine their therapeutic and diagnostic potential for managing toxin-related challenges. We also explore recent advancements and offer critical insights into the design and clinical implementation of ATNs.
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Nanopartículas , Humanos , Animais , Antitoxinas/uso terapêutico , Antitoxinas/química , Antitoxinas/farmacologia , Nanotecnologia/métodos , Desenho de FármacosRESUMO
Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state-of-the-art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti-tumor immune responses. The study encompasses various facets, including integrating biomaterial-based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines.
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Vacinas Anticâncer , Imunoterapia , Nanoestruturas , Neoplasias , Humanos , Vacinas Anticâncer/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Nanoestruturas/química , Imunoterapia/métodos , Animais , Microambiente Tumoral , NanovacinasRESUMO
Genome editing involves precise modification of specific nucleotides in the genome using nucleases like CRISPR/Cas, ZFN, or TALEN, leading to increased efficiency of homologous recombination (HR) for gene editing, and it can result in gene disruption events via non-homologous end joining (NHEJ) or homology-driven repair (HDR). Genome editing, particularly CRISPR-Cas9, revolutionizes vaccine development by enabling precise modifications of pathogen genomes, leading to enhanced vaccine efficacy and safety. It allows for tailored antigen optimization, improved vector design, and deeper insights into host genes' impact on vaccine responses, ultimately enhancing vaccine development and manufacturing processes. This review highlights different types of genome editing methods, their associated risks, approaches to overcome the shortcomings, and the diverse roles of genome editing.
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Sistemas CRISPR-Cas , Edição de Genes , Edição de Genes/métodos , Humanos , Animais , Vacinas/imunologia , Vacinas/genética , Desenvolvimento de VacinasRESUMO
INTRODUCTION: With the increase in the elderly population and the prevalence of multiple medical conditions, medication adherence, and efficacy have become crucial for the effective management of their health. The aging population faces unique challenges that need to be addressed through advancements in drug delivery systems and formulation technologies. AREAS COVERED: The current review highlights the recent advances in dosage form design for older individuals, with consideration of their specific physiological and cognitive changes. Various dosage forms, such as modified-release tablets/capsules, chewable tablets, and transdermal patches, can be tailored to meet the specific needs of elderly patients. Advancements in drug delivery systems, such as nanotherapeutics, additive manufacturing (three-dimensional printing), and drug-food combinations, improve drug delivery and efficacy and overcome challenges, such as dysphagia and medication adherence. EXPERT OPINION: Regulatory guidelines and considerations are crucial in ensuring the safe utilization of medications among older adults. Important factors to consider include geriatric-specific guidelines, safety considerations, labeling requirements, clinical trial considerations, and adherence and accessibility considerations.
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Sistemas de Liberação de Medicamentos , Humanos , Idoso , Comprimidos , Cápsulas , Formas de DosagemRESUMO
Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological tools, opening new possibilities. This article delves deeply into the concept of "tumor-derived systems", an umbrella term for tools sourced from the tumor that aid in combatting it. It includes cancer cell membrane-coated nanoparticles (for tumor theranostics), extracellular vesicles (for tumor diagnosis/therapy), tumor cell lysates (for cancer vaccine development), and engineered cancer cells/organoids (for cancer research). This review seeks to offer a complete overview of the tumor-derived materials that are utilized in cancer research, as well as their current stages of development and implementation. It is aimed primarily at researchers working at the interface of cancer biology and biomedical engineering, and it provides vital insights into this fast-growing topic.
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Collagen-based hydrogels have emerged as a highly promising platform for diverse applications in ophthalmology, spanning from drug delivery systems to biomedical interventions. This review explores the diverse sources of collagen, which give rise to different types of collagen protein. The critical isolation and purification steps are discussed, emphasizing their pivotal role in preparing collagen for biomedical use. To ensure collagen quality and purity, and the suitability of collagen for targeted applications, a comprehensive characterization and quality control are essential, encompassing assessments of its physical, chemical, and biological properties. Also, various cross-linking collagen methods have been examined for providing insight into this crucial process. This comprehensive review delves into every facet of collagen and explores the wide-ranging applications of collagen-based hydrogels, with a particular emphasis on their use in drug delivery systems and their potential in diverse biomedical interventions. By consolidating current knowledge and advancements in the field, this review aims to provide a detailed overview of the utilization of engineered collagen-based hydrogels in ocular therapeutics.
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Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core selection, approaches for coating nanoparticle cores with the cell membrane, and characterization methods. Moreover, this review underscores strategies employed to enhance the multi-functionality of these nanosystems, including lipid insertion, membrane hybridization, metabolic engineering, and genetic modification. Additionally, the applications of these bioinspired nanosystems in cancer diagnosis and therapeutics are discussed, along with the recent advances in this field. Through a comprehensive exploration of membrane-coated nanosystems, this review provides valuable insights into their potential for precise cancer theranostics.
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Chitosan, a biocompatible and biodegradable polysaccharide derived from chitin, has surfaced as a material of promise for drug delivery and biomedical applications. Different chitin and chitosan extraction techniques can produce materials with unique properties, which can be further modified to enhance their bioactivities. Chitosan-based drug delivery systems have been developed for various routes of administration, including oral, ophthalmic, transdermal, nasal, and vaginal, allowing for targeted and sustained release of drugs. Additionally, chitosan has been used in numerous biomedical applications, such as bone regeneration, cartilage tissue regeneration, cardiac tissue regeneration, corneal regeneration, periodontal tissue regeneration, and wound healing. Moreover, chitosan has also been utilized in gene delivery, bioimaging, vaccination, and cosmeceutical applications. Modified chitosan derivatives have been developed to improve their biocompatibility and enhance their properties, resulting in innovative materials with promising potentials in various biomedical applications. This article summarizes the recent findings on chitosan and its application in drug delivery and biomedical science.
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Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells.
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Materiais Biocompatíveis , Neoplasias , Humanos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Neoplasias/patologia , Imunoterapia/métodos , Células-Tronco Neoplásicas/patologia , Lipídeos , Microambiente TumoralRESUMO
Globally, diabetic nephropathy (DN) is the foremost cause of end-stage renal disease. With the incidence of diabetes increasing day by day, DN's occurrence is expected to surge to pandemic proportions. Current available therapeutic interventions associated with DN emphasize blood pressure, glycemia and lipid control while ignoring DN's progression mechanism at a molecular level. This review sheds light on the molecular insights involved in DN to help understand the initiation and progression pattern. Further, we summarize novel strategies with reported applications in developing a nanomedicine-based platform for DN-targeted drug delivery to improve drug efficacy and safety.