Anticancer Platelet-Mimicking Nanovehicles.
Ontology highlight
ABSTRACT:
SUBMITTER: Hu Q
PROVIDER: S-EPMC4998740 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Anticancer Platelet-Mimicking Nanovehicles.
Hu Quanyin Q Sun Wujin W Qian Chengen C Wang Chao C Bomba Hunter N HN Gu Zhen Z
Advanced materials (Deerfield Beach, Fla.) 20150929 44
A core-shell nanovehicle coated with a platelet membrane (PM) is developed for targeted and site-specific delivery of an extracellularly active drug and an intracellular functional small-molecular drug, leading to enhanced antitumor efficacy. This PM-coated nanovehicle can also effectively eliminate the circulating tumor cells in vivo and inhibit development of tumor metastasis. ...[more]
Similar Datasets
Project description:Rational: Interstitial brachytherapy (BT) is a promising radiation therapy for cancer; however, the efficacy of BT is limited by tumor radioresistance. Recent advances in materials science and nanotechnology have offered many new opportunities for BT. Methods: In this work, we developed a biomimetic nanotheranostic platform for enhanced BT. Core-shell Au@AuPd nanospheres (CANS) were synthesized and then encapsulated in platelet (PLT)-derived plasma membranes. Results: The resulting PLT/CANS nanoparticles efficiently evaded immune clearance and specifically accumulated in tumor tissues due to the targeting capabilities of the PLT membrane coating. Under endoscopic guidance, a BT needle was manipulated to deliver appropriate radiation doses to orthotopic colon tumors while sparing surrounding organs. Accumulated PLT/CANS enhanced the irradiation dose deposition in tumor tissue while alleviating tumor hypoxia by catalyzing endogenous H2O2 to produce O2. After treatment with PLT/CANS and BT, 100% of mice survived for 30 days. Conclusions: Our work presents a safe, robust, and efficient strategy for enhancing BT outcomes when adapted to treatment of intracavitary and unresectable tumors.
| S-EPMC8210607 | biostudies-literature
Project description:In the bone marrow, the interaction of progenitor cells with the vasculature is fundamental for the release of blood cells into circulation. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising protein biomaterial for bone marrow tissue engineering, because of its tunable architecture and mechanical properties, the capacity to incorporate labile compounds without loss of bioactivity and the demonstrated ability to support blood cell formation without premature activation. In this study, we fabricated a custom perfusion chamber to contain a multi-channel lyophilized silk sponge mimicking the vascular network in the bone marrow niche. The perfusion system consisted in an inlet and an outlet and 2 splitters that allowed funneling flow in each single channel of the silk sponge. Computational Fluid Dynamic analysis demonstrated that this design permitted confined flow inside the vascular channels. The silk channeled sponge supported efficient platelet release from megakaryocytes (Mks). After seeding, the Mks localized along SDF-1? functionalized vascular channels in the sponge. Perfusion of the channels allowed the recovery of functional platelets as demonstrated by increased PAC-1 binding upon thrombin stimulation. Further, increasing the number of channels in the silk sponge resulted in a proportional increase in the numbers of platelets recovered, suggesting applicability to scale-up for platelet production. In conclusion, we have developed a scalable system consisting of a multi-channeled silk sponge incorporated in a perfusion chamber that can provide useful technology for functional platelet production ex vivo.
| S-EPMC6082392 | biostudies-literature
Project description:Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.
| S-EPMC8061396 | biostudies-literature
Project description:The aberrant expression of endocytic epidermal growth factor receptors (EGFRs) in cancer cells has emerged as a key target for therapeutic intervention. Here, we describe for the first time a state-of-the-art design for a heparan sulfate (HS) oligosaccharide-based nanovehicle to target EGFR-overexpressed cancer cells in cellular heterogeneity. An ELISA plate IC50 inhibition assay and surface plasma resonance (SPR) binding assay of structurally well-defined HS oligosaccharides showed that 6-O-sulfation (6-O-S) and 6-O-phosphorylation (6-O-P) of HS tetrasaccharides significantly enhanced EGFR cognate growth factor binding. The conjugation of these HS ligands to multivalent fluorescent gold nanoparticles (AuNPs) enabled the specific and efficient targeting of EGFR-overexpressed cancer cells. In addition, this heparinoid-nanovehicle exhibited selective homing to NPs in cancer cells in three-dimensional (3D) coculture spheroids, thus providing a novel target for cancer therapy and diagnostics in the tumor microenvironment (TME).
| S-EPMC8179433 | biostudies-literature
Project description:Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and (iv) heteromultivalent presentation of ligands that mediate adhesion to both von Willebrand Factor and collagen, as well as specific clustering to activated platelets. Platelet-like nanoparticles (PLNs) exhibit enhanced surface-binding compared to spherical and rigid discoidal counterparts and site-selective adhesive and platelet-aggregatory properties under physiological flow conditions in vitro. In vivo studies in a mouse model demonstrated that PLNs accumulate at the wound site and induce ?65% reduction in bleeding time, effectively mimicking and improving the hemostatic functions of natural platelets. We show that both the biochemical and biophysical design parameters of PLNs are essential in mimicking platelets and their hemostatic functions. PLNs offer a nanoscale technology that integrates platelet-mimetic biophysical and biochemical properties for potential applications in injectable synthetic hemostats and vascularly targeted payload delivery.
| S-EPMC4246005 | biostudies-literature
Project description:BACKGROUNDS:Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients' compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process. METHODS:In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer. RESULTS:Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability. CONCLUSIONS:Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.
| S-EPMC7118915 | biostudies-literature
Project description:Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate via responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation through the IEDDA reaction. The hierarchically regulated and locally confined Dox liberation led to dramatically decreased side-effects that were much lower than those of the clinical Doxorubicin Hydrochloride Liposomal Injection (Doxil), while the antitumor therapeutic effect was potent.
| S-EPMC8150104 | biostudies-literature
Project description:Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-? and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The RNA nanoparticles were delivered to macrophages specifically. The degree of immunostimulation greatly depended on the size, shape and number of the payload per nanoparticles. Stronger immune response was observed when the number of adjuvants per polygon was increased, demonstrating the advantage of shape transition from triangle to pentagon.
| S-EPMC4150753 | biostudies-literature
Project description:BACKGROUND:Currently, the diagnosis and treatment of neuroblastomas-the most frequent solid tumors in children-exploit the norepinephrine transporter (hNET) via radiolabeled norepinephrine analogs. We aim to develop a nanomedicine-based strategy towards precision therapy by targeting hNET cell-surface protein with hNET-derived homing peptides. RESULTS:The peptides (seq. GASNGINAYL and SLWERLAYGI) were shown to bind high-resolution homology models of hNET in silico. In particular, one unique binding site has marked the sequence and structural similarities of both peptides, while most of the contribution to the interaction was attributed to the electrostatic energy of Asn and Arg (<?-?228 kJ/mol). The peptides were comprehensively characterized by computational and spectroscopic methods showing ~?21% ?-sheets/aggregation for GASNGINAYL and ~?27% ?-helix for SLWERLAYGI. After decorating 12-nm ferritin-based nanovehicles with cysteinated peptides, both peptides exhibited high potential for use in actively targeted neuroblastoma nanotherapy with exceptional in vitro biocompatibility and stability, showing minor yet distinct influences of the peptides on the global expression profiles. Upon binding to hNET with fast binding kinetics, GASNGINAYLC peptides enabled rapid endocytosis of ferritins into neuroblastoma cells, leading to apoptosis due to increased selective cytotoxicity of transported payload ellipticine. Peptide-coated nanovehicles significantly showed higher levels of early apoptosis after 6 h than non-coated nanovehicles (11% and 7.3%, respectively). Furthermore, targeting with the GASNGINAYLC peptide led to significantly higher degree of late apoptosis compared to the SLWERLAYGIC peptide (9.3% and 4.4%, respectively). These findings were supported by increased formation of reactive oxygen species, down-regulation of survivin and Bcl-2 and up-regulated p53. CONCLUSION:This novel homing nanovehicle employing GASNGINAYLC peptide was shown to induce rapid endocytosis of ellipticine-loaded ferritins into neuroblastoma cells in selective fashion and with successful payload. Future homing peptide development via lead optimization and functional analysis can pave the way towards efficient peptide-based active delivery of nanomedicines to neuroblastoma cells.
| S-EPMC7359476 | biostudies-literature
Project description:Cancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell-cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy.
| S-EPMC8627085 | biostudies-literature