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1.
Carbohydr Polym ; 340: 122311, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38858027

RESUMEN

Modified biopolymers that are based on prebiotics have been found to significantly contribute to immunomodulatory events. In recent years, there has been a growing use of modified biomaterials and polymer-functionalized nanomaterials in the treatment of various tumors by activating immune cells. However, the effectiveness of immune cells against tumors is hindered by several biological barriers, which highlights the importance of harnessing prebiotic-based biopolymers to enhance host defenses against cancer, thus advancing cancer prevention strategies. Inulin, in particular, plays a crucial role in activating immune cells and promoting the secretion of cytokines. Therefore, this mini-review aims to emphasize the importance of inulin in immunomodulatory responses, the development of inulin-based hybrid biopolymers, and the role of inulin in enhancing immunity and modifying cell surfaces. Furthermore, we discuss the various approaches of chemical modification for inulin and their potential use in cancer treatment, particularly in the field of cancer immunotherapy.


Asunto(s)
Materiales Biocompatibles , Inulina , Neoplasias , Inulina/química , Inulina/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Inmunoterapia/métodos
2.
Acta Biomater ; 180: 140-153, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38604467

RESUMEN

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.


Asunto(s)
Neoplasias de la Mama , Galio , Hidrogeles , Hidrogeles/química , Galio/química , Galio/farmacología , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Animales , Línea Celular Tumoral , Inyecciones , Fototerapia , Ratones Desnudos , Ratones , Terapia Fototérmica , Ratones Endogámicos BALB C
3.
Biomacromolecules ; 25(3): 1959-1971, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38379131

RESUMEN

Triple-negative breast cancer (TNBC) presents treatment challenges due to a lack of detectable surface receptors. Natural killer (NK) cell-based adaptive immunotherapy is a promising treatment because of the characteristic anticancer effects of killing malignant cells directly by secreting cytokines and lytic granules. To maximize the cancer recognition ability of NK cells, biomaterial-mediated ex vivo cell surface engineering has been developed for sufficient cell membrane immobilization of tumor-targeting ligands via hydrophobic anchoring. In this study, we optimized amphiphilic balances of NK cell coating materials composed of CD44-targeting hyaluronic acid (HA)-poly(ethylene glycol) (PEG)-lipid to improve TNBC recognition and the anticancer effect. Changes in the modular design of our material by differentiating hydrophilic PEG length and incorporating lipid amount into HA backbones precisely regulated the amphiphilic nature of HA-PEG-lipid conjugates. The optimized biomaterial demonstrated improved anchoring into NK cell membranes and facilitating the surface presentation level of HA onto NK cell surfaces. This led to enhanced cancer targeting via increasing the formation of immune synapse, thereby augmenting the anticancer capability of NK cells specifically toward CD44-positive TNBC cells. Our approach addresses targeting ability of NK cell to solid tumors with a deficiency of surface tumor-specific antigens while offering a valuable material design strategy using amphiphilic balance in immune cell surface engineering techniques.


Asunto(s)
Ácido Hialurónico , Neoplasias de la Mama Triple Negativas , Humanos , Ácido Hialurónico/química , Línea Celular Tumoral , Materiales Biocompatibles/farmacología , Células Asesinas Naturales , Lípidos , Receptores de Hialuranos/metabolismo
4.
Microb Cell Fact ; 23(1): 2, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172950

RESUMEN

Haloarchaea produce bacterioruberin, a major C50 carotenoid with antioxidant properties that allow for its potential application in the food, cosmetic, and pharmaceutical industries. This study aimed to optimize culture conditions for total carotenoid, predominantly comprising bacterioruberin, production using Halorubrum ruber MBLA0099. A one-factor-at-a-time and statistically-based experimental design were applied to optimize the culture conditions. Culture in the optimized medium caused an increase in total carotenoid production from 0.496 to 1.966 mg L- 1 Maximal carotenoid productivity was achieved in a 7-L laboratory-scale fermentation and represented a 6.05-fold increase (0.492 mg L-1 d-1). The carotenoid extracts from strain MBLA0099 exhibited a 1.8-10.3-fold higher antioxidant activity in vitro, and allowed for a higher survival rate of Caenorhabditis elegans under oxidative stress conditions. These results demonstrated that Hrr. ruber MBLA0099 has significant potential as a haloarchaon for the commercial production of bacterioruberin.


Asunto(s)
Antioxidantes , Halorubrum , Carotenoides
5.
Biomacromolecules ; 25(1): 222-237, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38130077

RESUMEN

Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acid-overexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module. Therefore, a 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-conjugated di-PEG-PBA (DSPEPEG-di(PEG-PBA) biomaterial was synthesized. The DSPEPEG-di(PEG-PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6.5 and 7.4. DSPEPEG-di(PEG-PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells. Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.


Asunto(s)
Ácido N-Acetilneuramínico , Neoplasias , Humanos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/uso terapéutico , Neoplasias/tratamiento farmacológico , Células Asesinas Naturales , Lípidos , Materiales Biocompatibles/uso terapéutico
6.
Biomacromolecules ; 25(1): 436-443, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38146913

RESUMEN

The use of nanocarriers decorated with penetration-enhancing agents (PEAs) is considered to be a promising approach for efficient transdermal delivery. In this study, we developed short amphiphilic skin-penetrating peptides (17 amino acids) that functioned not only as PEAs but also as building blocks of nanocarriers without the incorporation of additional macromolecules for self-assembly and guest molecule encapsulation. Interestingly, varying only two amino acids in the hydrophobic moiety of the peptides resulted in significantly different self-assembly behavior, thermal stability, protease resistance, and skin-penetration efficiency in a human skin model. The analysis of the peptide secondary structure revealed that such characteristic changes arose due to the sequence variation-mediated conformational change in the hydrophobic block. These findings hold significant promise for the development of simple and effective delivery systems exhibiting controllable supramolecular properties.


Asunto(s)
Péptidos , Piel , Humanos , Péptidos/química , Administración Cutánea , Absorción Cutánea , Aminoácidos
7.
Small ; 20(24): e2306738, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38161257

RESUMEN

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.


Asunto(s)
Receptores de Hialuranos , Ácido Hialurónico , Inmunoterapia , Células Asesinas Naturales , Células Asesinas Naturales/inmunología , Receptores de Hialuranos/metabolismo , Animales , Humanos , Inmunoterapia/métodos , Ácido Hialurónico/química , Línea Celular Tumoral , Ligandos , Ratones , Polietilenglicoles/química , Neoplasias/terapia , Neoplasias/inmunología
8.
Adv Healthc Mater ; 13(5): e2302313, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38124514

RESUMEN

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.


Asunto(s)
Vesículas Extracelulares , Nanopartículas Multifuncionales , Neoplasias Pancreáticas , Humanos , Lectinas/metabolismo , Polisacáridos , Neoplasias Pancreáticas/diagnóstico , Vesículas Extracelulares/metabolismo
9.
Nano Converg ; 10(1): 56, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38097911

RESUMEN

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

10.
Bioconjug Chem ; 34(10): 1789-1801, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37726892

RESUMEN

Natural killer (NK) cells exhibit a good therapeutic efficacy against various malignant cancer cells. However, the therapeutic efficacy of plain NK cells is relatively low due to inadequate selectivity for cancer cells. Therefore, to enhance the targeting selectivity and anticancer efficacy of NK cells, we have rationally designed a biomaterial-mediated ex vivo surface engineering technique for the membrane decoration of cancer recognition ligands onto NK cells. Our designed lipid conjugate biomaterial contains three major functional moieties: (1) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid for cell membrane anchoring, (2) polyethylene glycol for intracellular penetration blocker, and (3) lactobionic acid (LBA) for cancer recognition. The biomaterial was successfully applied to NK cell surfaces (LBA-NK) to enhance recognition and anticancer functionalities, especially toward asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma. Highly efficient and homogeneous NK cell surface editing was achieved with a simple coating process while maintaining intrinsic properties of NK cells. LBA-NK cells showed potential ASGPR-mediated tumor cell binding (through LBA-ASGPR interaction) and thereby significantly augmented anticancer efficacies against HepG2 liver cancer cells. Thus, LBA-NK cells can be a novel engineering strategy for the treatment of liver cancers via facilitated immune synapse interactions in comparison with currently available cell therapies.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Materiales Biocompatibles/metabolismo , Células Asesinas Naturales , Lípidos/uso terapéutico
11.
Nanomaterials (Basel) ; 13(13)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37446533

RESUMEN

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

12.
Biomater Res ; 27(1): 59, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37344853

RESUMEN

Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell-cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell-surface modulation, a few cell recognition moieties, and how their interplay in cell-cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications.

13.
Macromol Biosci ; 23(11): e2300159, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37319369

RESUMEN

Immune cell engineering is an active field of ongoing research that can be easily applied to nanoscale biomedicine as an alternative to overcoming limitations of nanoparticles. Cell membrane coating and artificial nanovesicle technology have been reported as representative methods with an advantage of good biocompatibility for biomimetic replication of cell membrane characteristics. Cell membrane-mediated biomimetic technique provides properties of natural cell membrane and enables membrane-associated cellular/molecular signaling. Thus, coated nanoparitlces (NPs) and artificial nanovesicles can achieve effective and extended in vivo circulation, enabling execution of target functions. While coated NPs and artificial nanovesicles provide clear advantages, much work remains before clinical application. In this review, first a comprehensive overview of cell membrane coating techniques and artificial nanovesicles is provided. Next, the function and application of various immune cell membrane types are summarized.


Asunto(s)
Materiales Biomiméticos , Nanopartículas , Neoplasias , Humanos , Membrana Celular , Neoplasias/terapia , Inmunoterapia
14.
Int J Biol Macromol ; 242(Pt 2): 124814, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37201889

RESUMEN

Metal nanoparticles have been tremendously utilised, such as; antibacterial and anticancer agents. Although metal nanoparticles exhibits antibacterial and anticancer activity, but the drawback of toxicity on normal cells limits their clinical applications. Therefore, improving the bioactivity of hybrid nanomaterial (HNM) and minimizing toxicity is of paramount importance for biomedical applications. Herein, a facile and simple double precipitation method was used to develop biocompatible and multifunctional HNM from antimicrobial chitosan, curcumin, ZnO and TiO2. In HNM, biomolecules chitosan and curcumin were used to control the toxicity of ZnO and TiO2 and improve their biocidal properties. The cytotxicological properties of the HNM was studied against human breast cancer (MDA-MB-231) and fibroblast (L929) cell lines. The antimicrobial activity of the HNM was examined against Escherichia coli and Staphylococcus aureus bacteria, via the well-diffusion method. In addition, the antioxidant property was evaluated by the radical scavenging method. These findings actively, support the ZTCC HNM potential, as an innovative biocidal agent for applications in the clinical and healthcare sectors.


Asunto(s)
Antiinfecciosos , Quitosano , Curcumina , Nanoestructuras , Óxido de Zinc , Humanos , Curcumina/farmacología , Óxido de Zinc/farmacología , Antibacterianos/farmacología
15.
Biomater Sci ; 11(13): 4537-4548, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37158297

RESUMEN

For the successful development of various cellular products in cancer immunotherapy, an effective ex vivo priming technique for immune cells is often required. Among a variety of immunomodulatory substances, tumor cell lysates (TCLs) have been considered a robust immune activator with high adjuvanticity and tumor antigen population. Therefore, the present study suggests a novel ex vivo dendritic cell (DC) priming technique that utilizes (1) squaric acid (SqA)-mediated oxidation of source tumor cells to obtain antigenic TCLs with an increased immunogenic potential and (2) a coacervate (Coa) colloidal complex as an exogenous TCL carrier. Elevated oxidation by SqA-treated source tumor cells resulted in an increased immunogenic potential, indicated by a high level of damage-associated molecular pattern molecules in TCLs that could sufficiently stimulate DCs. Moreover, to effectively deliver these exogenous immunomodulating TCL DCs, Coa (i.e., a colloidal micro-carrier using cationic mPEGylated poly(ethylene arginyl aspartate diglyceride) and anionic heparin) was utilized for the sustained release of cargo TCLs and for preserving their bioactivity. Coa-mediated ex vivo delivery of SqA-treated TCLs (SqA-TCL-Coa) effectively promoted DC maturation through the enhanced uptake of antigens into target DCs, increased expression of DC activation markers, facilitated secretion of pro-inflammatory cytokines from activated DCs, and improved major histocompatibility complex-I dependent cross-presentation of a colorectal cancer specific antigen. Therefore, based on antigenic and adjuvant behaviors, our Coa-mediated exogenous delivery of SqA-TCL could be a promising application as a facile ex vivo DC priming strategy for further cell-based cancer immunotherapies.


Asunto(s)
Neoplasias , Humanos , Neoplasias/metabolismo , Antígenos de Neoplasias , Reactividad Cruzada , Citocinas/metabolismo , Células Dendríticas
16.
Gels ; 9(4)2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37102931

RESUMEN

Colon cancer is a significant health concern. The development of effective drug delivery systems is critical for improving treatment outcomes. In this study, we developed a drug delivery system for colon cancer treatment by embedding 6-mercaptopurine (6-MP), an anticancer drug, in a thiolated gelatin/polyethylene glycol diacrylate hydrogel (6MP-GPGel). The 6MP-GPGel continuously released 6-MP, the anticancer drug. The release rate of 6-MP was further accelerated in an acidic or glutathione environment that mimicked a tumor microenvironment. In addition, when pure 6-MP was used for treatment, cancer cells proliferated again from day 5, whereas a continuous supply of 6-MP from the 6MP-GPGel continuously suppressed the survival rate of cancer cells. In conclusion, our study demonstrates that embedding 6-MP in a hydrogel formulation can improve the efficacy of colon cancer treatment and may serve as a promising minimally invasive and localized drug delivery system for future development.

17.
Colloids Surf B Biointerfaces ; 226: 113294, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37043951

RESUMEN

A variety of therapeutic approaches using liquid metal (LM) have been intensively investigated, due to its unique physico-chemical properties that include high surface tension, fluidity, shape deformability, thermal conductivity, and electrical conductivity. Among a series of LMs, the relatively lower toxicity and minimal volatility of gallium (Ga)-based LMs (GaLMs) enables their usage in a series of potential biomedical applications, especially implantable platforms, to treat multiple diseases. In addition, the highly efficient conversion of light energy into thermal or chemical energy via GaLMs has led to recent developments in photothermal and photodynamic applications for anticancer treatments. As attractive photothermal agents or photosensitizers, a systematic interpretation of the structural characteristics and photo-responsive behaviors of GaLMs is necessary to develop effective anticancer engineering applications. Therefore, the aim of this review is to provide a comprehensive summary of currently suggested GaLM-mediated photo-therapeutic cancer treatments. In particular, the review summarizes (1) surface coating techniques to form stable and multifunctional GaLM particulates, (2) currently investigated GaLM-mediated photothermal and photodynamic anticancer therapies, (3) synergistic efficacies with the aid of additional interventions, and (4) 3D composite gels embedded with GaLMs particles, to convey the potential technological advances of LM in this field.


Asunto(s)
Antiinfecciosos , Galio , Fotoquimioterapia , Galio/farmacología , Galio/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Penicilinas , Antiinfecciosos/uso terapéutico , Expectorantes
18.
Biomater Sci ; 10(20): 5968-5979, 2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36048163

RESUMEN

Effective exogenous delivery of interleukin (IL)-15 to natural killer (NK) cells with subsequent anticancer efficacy could be a promising immune cell-based cancer immunotherapy. For the protection of encapsulated cargo IL-15 while maintaining its bioactivity under physiological conditions, we utilized a coacervate (Coa) consisting of a cationic methoxy polyethylene glycol-poly(ethylene arginyl aspartate diglyceride) (mPEG-PEAD) polymer, anionic counterpart heparin, and cargo IL-15. mPEGylation into the backbone cation effectively preserved the colloidal stability of Coa in harsh environments and enhanced the protection of cargo IL-15 than normal Coa without mPEGylation. Proliferation and anticancer efficacy of primed NK cells through co-culture with multiple cancer cell lines were enhanced in the mPEG-Coa group due to the maintained bioactivity of cargo IL-15 during the ex vivo expansion of NK cells. These facilitated functions of NK cells were also supported by the increased expression of mRNAs related to anticancer effects of NK cells, including cytotoxic granules, death ligands, anti-apoptotic proteins, and activation receptors. In summary, our Coa-mediated exogenous IL-15 delivery could be an effective ex vivo priming technique for NK cells with sustained immune activation that can effectively facilitate its usage for cancer immunotherapy.


Asunto(s)
Diglicéridos , Interleucina-15 , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/farmacología , Ácido Aspártico , Diglicéridos/metabolismo , Diglicéridos/farmacología , Etilenos/metabolismo , Etilenos/farmacología , Heparina/farmacología , Interleucina-15/metabolismo , Interleucina-15/farmacología , Células Asesinas Naturales , Polietilenglicoles/farmacología
19.
Biomater Adv ; 140: 213059, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35961186

RESUMEN

Once administrated, intercellular adhesion to recognize and/or arrest target cells is essential for specific treatments, especially for cancer or tumor. However, immune cells administrated into the tumor-microenvironment could lose their intrinsic functionalities such as target recognition ability, resulting in an ineffective cancer immunotherapy. Various manipulation techniques for decorating functional moieties onto cell surface and enhancing target recognition have been developed. A hydrophobic interaction-mediated ex-vivo cell surface engineering using lipid-based biomaterials could be a state-of-the-art engineering technique that could achieve high-efficiency cell surface modification by a single method without disturbance of intrinsic characteristics of cells. In this regard, this review provides design principles for the development of lipid-based biomaterials with a linear structure of lipid, polyethylene glycol, and functional group, strategies for the synthesis process, and their practical applications in biomedical engineering. Especially, we provide new insights into the development of a novel surface coating techniques for natural killer (NK) cells with engineering decoration of cancer targeting moieties on their cell surfaces. Among immune cells, NK cells are interesting cell population for substituting T cells because of their excellent safety and independent anticancer efficacy. Thus, optimal strategies to select cancer-type-specific targeting moieties and present them onto the surface of immune cells (especially, NK cells) using lipid-based biomaterials could provide additional tools to capture cancer cells for developing novel immune cell therapy products. Enhanced anticancer efficacies by surface-engineered NK cells have been demonstrated both in vitro and in vivo. Therefore, it could be speculated that recent progresses in cell surface modification technology via lipid-based biomaterials could strengthen immune surveillance and immune synapses for utilization in a next-generation cancer immunotherapy, beyond currently available genetic engineering tool such as chimeric antigen receptor-mediated immune cell modulation.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Materiales Biocompatibles/metabolismo , Humanos , Células Asesinas Naturales , Lípidos , Neoplasias/terapia , Receptores Quiméricos de Antígenos/genética , Microambiente Tumoral
20.
Pharmaceutics ; 14(7)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35890254

RESUMEN

Tumor cell lysates (TCLs) are a good immunogenic source of tumor-associated antigens. Since whole necrotic TCLs can enhance the maturation and antigen-presenting ability of dendritic cells (DCs), multiple strategies for the exogenous delivery of TCLs have been investigated as novel cancer immunotherapeutic solutions. The TCL-mediated induction of DC maturation and the subsequent immunological response could be improved by utilizing various material-based carriers. Enhanced antitumor immunity and cancer vaccination efficacy could be eventually achieved through the in vivo administration of TCLs. Therefore, (1) important engineering methodologies to prepare antigen-containing TCLs, (2) current therapeutic approaches using TCL-mediated DC activation, and (3) the significant sequential mechanism of DC-based signaling and stimulation in adaptive immunity are summarized in this review. More importantly, the recently reported developments in biomaterial-based exogenous TCL delivery platforms and co-delivery strategies with adjuvants for effective cancer vaccination and antitumor effects are emphasized.

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