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Creators/Authors contains: "Santos, Hélder A."

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  1. Abstract

    The effective removal of complex pollutants is extremely challenging for environmental and material science, especially pollutants including detergents and pesticides do not decompose or degrade in the aquatic environment which cannot be easily removed. Here, a novel biocompatible superparamagnetic nanocomposite integrating the advantages of porous silicon nanoparticles is developed, the chelation ability of chitosan, and graphene‐oxide‐iron that can simultaneously adsorb complex hydrophobic and hydrophilic pollutants on their internal and external surfaces which have significantly improved pollutant removal efficiency over the current existing methods. A porous silicon nanoparticle (PSi) conjugated magnetite‐chitosan‐reduced graphene oxide (MCRGO) nanoparticles (PSi‐MCRGO) are synthesized for complete removal of detergent, pesticide, and toxic heavy metals cadmium and lead ions from water at a favorable room temperature. The adsorption behavior of the nanocomposites fits well with the Freundlich isotherm and pseudo‐second‐order kinetics model by adsorption mechanism. Moreover, the fresh and recycled nanocomposites are easily separated by an external magnetic field for reusability due to super magnetite response and show high binding capacity for toxic heavy metal ions. Furthermore, the nanocomposites are biocompatible and reusable, and for the fourth time, recycled nanocomposites can completely remove toxic heavy metals. Overall, the novel nanocomposites completely remove complex pollutants which hold great potential for real water treatment.

     
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  2. Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.

     
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  3. Abstract

    Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities to control the resulting subclasses of antibodies produced, which can mediate effector functions relevant to distinct disease settings. Here, it is found that three scaffold‐based vaccines, fabricated from poly(lactide‐co‐glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce robust, long‐term antibody responses to a model peptide antigen gonadotropin‐releasing hormone with single‐shot immunization. Compared to a bolus vaccine, PLG vaccines prolong germinal center formation and T follicular helper cell responses. Altering the presentation and release of the adjuvant (cytosine‐guanosine oligodeoxynucleotide, CpG) tunes the resulting IgG subclasses. Further, PLG vaccines elicit strong humoral responses against disease‐associated antigens HER2 peptide and pathogenicE. coli, protecting mice againstE. colichallenge more effectively than a bolus vaccine. Scaffold‐based vaccines may thus enable potent, durable and versatile humoral immune responses against disease.

     
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  4. Abstract

    Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte‐macrophage colony‐stimulating factor and cytosine‐phosphodiester‐guanine‐rich oligonucleotides, are combined with spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), loaded with p53 activator Nutlin‐3a (Nut‐3a) for combined chemoimmunotherapy. The Sp‐AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut‐3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.

     
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