Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

Wang, Shiqi; Fontana, Flavia; Shahbazi, Mohammad‐Ali; Santos, Hélder A.

doi:10.1039/d1cc00811k

Cited by 35 publications

(22 citation statements)

References 124 publications

(267 reference statements)

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“…Next, in the presence of pyridinium p ‐toluenesulfonate, Ox‐DEX polymer was treated with 2‐methoxypropene to yield partially oxidized acetalated dextran (Ox‐AcDEX) polymer (Scheme 1a ), which can be fabricated into conjugates via the formation of Schiff base linkages. [ 27 ] We tried to conjugate Ox‐AcDEX polymer with a MUC1 CTLp with the sequence of TSAPDTRPAP, and then prepared the nanoparticles (NPs) by the double emulsion method. Very low conjugation efficiency of peptides in the NPs was found, possibly due to the cleavage of the formed Schiff base in dichloromethane used to prepare the NPs.…”

Section: Resultsmentioning

confidence: 99%

Developing Acid‐Responsive Glyco‐Nanoplatform Based Vaccines for Enhanced Cytotoxic T‐lymphocyte Responses Against Cancer and SARS‐CoV‐2

Gao

Zhao

Dong

et al. 2021

Adv Funct Materials

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Cytotoxic T‐lymphocytes (CTLs) are central for eliciting protective immunity against malignancies and infectious diseases. Here, for the first time, partially oxidized acetalated dextran nanoparticles (Ox‐AcDEX NPs) with an average diameter of 100 nm are fabricated as a general platform for vaccine delivery. To develop effective anticancer vaccines, Ox‐AcDEX NPs are conjugated with a representative CTL peptide epitope (CTLp) from human mucin‐1 (MUC1) with the sequence of TSAPDTRPAP (referred to as Mp1) and an immune‐enhancing adjuvant R837 (referred to as R) via imine bond formation affording AcDEX‐(imine)‐Mp1‐R NPs. Administration of AcDEX‐(imine)‐Mp1‐R NPs results in robust and long‐lasting anti‐MUC1 CTL immune responses, which provides mice with superior protection from the tumor. To verify its universality, this nanoplatform is also exploited to deliver epitopes from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to prevent coronavirus disease 2019 (COVID‐19). By conjugating Ox‐AcDEX NPs with the potential CTL epitope of SARS‐CoV‐2 (referred to as Sp) and R837, AcDEX‐(imine)‐Sp‐R NPs are fabricated for anti‐SARS‐CoV‐2 vaccine candidates. Several epitopes potentially contributing to the induction of potent and protective anti‐SARS‐CoV‐2 CTL responses are examined and discussed. Collectively, these findings shed light on the universal use of Ox‐AcDEX NPs to deliver both tumor‐associated and virus‐associated epitopes.

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Section: Resultsmentioning

confidence: 99%

Developing Acid‐Responsive Glyco‐Nanoplatform Based Vaccines for Enhanced Cytotoxic T‐lymphocyte Responses Against Cancer and SARS‐CoV‐2

Gao

Zhao

Dong

et al. 2021

Adv Funct Materials

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“…98,99 Self-assembly of polysaccharide chains can be employed for NPs formation as well, which is another supramolecular avenue. 100 Commonly, hydrophilic polysaccharides are functionalised with hydrophobic moieties (bile acids, fatty acids or cholesterol) that will aggregate in aqueous environment leading to micellar structures (Scheme 2d). 101,102 As such, NPs with hydrophobic core and hydrophilic polysaccharide shell are obtained.…”

Section: Crosslinking and Aggregation Strategiesmentioning

confidence: 99%

Polysaccharide nanoparticles: from fabrication to applications

2021

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“…In this regard, some natural oligosaccharides, such as chitosan, dextran, and cyclodextrins, are widely used in the biomedical field as precursors for developing responsive vehicles. [ 38 ] For instance, a series of pH‐triggered cyclodextrin‐containing biomaterials based on acetalization chemistry has been well demonstrated ( Figure ). [ 39 ] More recently, the same research group successfully produced a microRNA‐33 antagonist (anti‐miR33)‐conjugated pH‐sensitive nanoplatform by using cyclodextrin‐based polymers.…”

Section: Smart Biomaterials For Treating Cardiovascular Diseasesmentioning

confidence: 99%

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

Tapeinos

Gao

Bauleth‐Ramos

et al. 2022

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the heart, leading to the two major subcategories of cerebrovascular and cardiovascular diseases (CVDs). Both cerebral and cardiovascular diseases (CCVDs) are prevalent, leading to high percentages of mortality and morbidity worldwide. [3,4] Over the years, several medical approaches have been used to treat these diseases. For example, mechanical thrombectomy and tissue plasminogen activator (tPA) administration are the standard therapies for treating ischemic stroke that can undoubtedly help numerous patients. However, limitations like the short time window for applying these therapies (≈3-6 h) and the transformation of ischemic stroke to hemorrhagic due to tPA administration constrains their use to most patients. Following the same rationale, the standard treatment for myocardial ischemia that leads to infarction uses thrombolytics like aspirin and tissue or urokinase plasminogen activator (uPA), in combination with antihypertensives to reduce blood pressure and nitroglycerine to widen the blood vessels. Nevertheless, similar side effects as in ischemic stroke inhibit their unconditioned use. Notably, most of the current commercial treatments are focused on the imminent effects of CCVDs without considering the post-ischemia side effects. In particular, blood flow restoration followed by damage mitigation in the brain or the heart is the primary goal of the current CCVDs' treatment. Although these treatments increase the patients' survival, and to a limited extent, attenuate the disease's symptoms, they are unable to properly cure the disease due to the detrimental side effects caused by vascular ischemia.Several "smart" strategies have been suggested to eliminate the restraints of the current medical treatments and improve their therapeutic outcome. [5,6] These strategies involve using biomaterials that can read the biochemical alterations in the diseased microenvironment and respond in predetermined ways. [7,8] These "smart" biomaterials or stimuli-responsive materials can alter their physicochemical properties or structure depending on various stimuli. Additionally, they can exert a therapeutic effect either by the release of an encapsulated therapeutic (e.g., tPA/uPA) [9,10] or because of an inherent property (e.g., antioxidant CeO 2 nanoparticles (NPs)). [11][12][13] It should be noted that the stimuli can be internal, like acidic pH, platelet activation, reactive oxygen species (ROS) concentration, and enzyme concentration, or external, like magnetic and electric fields, ultrasound, and light. The reason why these stimuliresponsive biomaterials are at the forefront of research lies in the complex pathophysiology of the CCVDs that renders simple Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasin...

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Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

Abstract: Acetalated dextran (Ac-DEX) is a pH-responsive dextran derivative polymer. Prepared by a simple acetalation reaction, Ac-DEX has tunable acid-triggered release profile. Despite its relatively short research history, Ac-DEX has shown...

Cited by 35 publications

References 124 publications

Developing Acid‐Responsive Glyco‐Nanoplatform Based Vaccines for Enhanced Cytotoxic T‐lymphocyte Responses Against Cancer and SARS‐CoV‐2

Developing Acid‐Responsive Glyco‐Nanoplatform Based Vaccines for Enhanced Cytotoxic T‐lymphocyte Responses Against Cancer and SARS‐CoV‐2

Polysaccharide nanoparticles: from fabrication to applications

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

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