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CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy
摘要: Combined photothermal and gene therapy provides a promising modality toward cancer treatment, yet facile integration and controlled codelivery of gene payloads and photothermal conversion agents (PTCAs) remains a great challenge. Inspired by the robust wet adhesion of marine mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%). Moreover, a successful calcium phosphate (CaP) coating via biomineralization was constructed on the cationic nanoparticle to prohibit premature release of siRNA. The CaP coating underwent biodegradation in weakly-acidic subcellular conditions (lysosomes). The synergistic integration of tertiary amines and catechol moieties on the subsequently exposed surfaces was demonstrated to feature the destabilization/disruption ability toward model cellular membranes via the greatly enhanced interfacial adhesion and interactions. Consequently, sufficient permeability of lysosomal membranes, and in turn, a high lysosomal escape efficiency, was realized, which then resulted in high gene silencing efficiencies via sufficient cytosolic delivery of siRNA. When an efficient knocking down (65%) of survivin (an inhibitor of apoptosis proteins) was combined with a subsequent photothermal ablation, remarkably higher therapeutic efficiencies were observed both in vitro and in vivo, as compared with monotherapy. The system may help to pave a new avenue on the utilization of bio-adhesive surfaces for handling the obstacles of combined photothermal and gene therapy.
关键词: porous polydopamine nanocarriers,bioadhesion,lysosomal escape,siRNA delivery,photothermal therapy
更新于2025-09-23 15:22:29
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Super-resolution imaging of self-assembled nanocarriers using quantitative spectroscopic analysis for cluster extraction
摘要: Self-assembled nanocarriers have inspired a range of applications for bioimaging, diagnostics, and drug delivery. Non-invasive visualization and characterization of nanocarriers are important for understanding their structure to function relationship. However, quantitative visualization of nanocarriers in the sample’s native environment remains challenging using existing technologies. Single-molecule localization microscopy (SMLM) has the potential to provide both high-resolution visualization and quantitative analysis of nanocarriers in their native environment. However, non-specific binding of fluorescent probes used in SMLM can introduce artifacts, which impose challenges in quantitative analysis of SMLM images. We showed the feasibility of using spectroscopic point accumulation for imaging in nanoscale topography (sPAINT) to visualize self-assembled polymersomes (PS) with molecular specificity. Furthermore, we analyzed the unique spectral signatures of Nile Red (NR) molecules bound to the PS to reject artifacts from non-specific NR bindings. We further developed quantitative spectroscopic analysis for cluster extraction (qSPACE) to increase the localization density by 4-fold compared to sPAINT; thus, reducing variations in PS size measurements to less than 5%. Finally, using qSPACE we quantitatively imaged PS at various concentrations in aqueous solutions with ~20-nm localization precision and 97% reduction in sample misidentification relative to conventional SMLM.
关键词: nanocarriers,Nile Red,super-resolution imaging,single-molecule localization microscopy,spectroscopic analysis,polymersomes
更新于2025-09-23 15:19:57
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Insight into the efficiency of oxygen introduced photodynamic therapy (PDT) and deep PDT against cancers with various assembled nanocarriers
摘要: Photodynamic therapy (PDT) has been used in the treatment of cancers and other benign diseases for several years in clinic. However, the hypoxia of tumors and the penetration limitation of excitation light to tissues can dramatically reduce the efficacy of PDT to cancers. To overcome these drawbacks, various assembled nanocarriers such as nanoparticles, nanocapsules, nanocrystals, and so on were introduced. The assembled nanocarriers have the ability of loading photosensitizers, delivering O2 into tumors, generating O2 in situ in tumors, as well as turning near-infrared (NIR) light, X-rays, and chemical energy into ultraviolet or visible light. Therefore, it is easy for the nanocarriers to improve the hypoxia microenvironment or increase the treatment depth of cancers, which will improve the efficiency of PDT to some degree. In recent years, a number of investigations were focused on these subjects. We will summarize the advances of nanocarriers in PDT, especially in O2 introduction PDT and deep PDT. The perspectives, challenges, and potential in translation of PDT will also be discussed.
关键词: Oxygen introduction,Photodynamic therapy (PDT),Cancers,Nanocarriers,Deep PDT
更新于2025-09-19 17:13:59
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Enhancement of curcumin antitumor efficacy and further photothermal ablation of tumor growth by single-walled carbon nanotubes delivery system <i>in vivo</i>
摘要: Curcumin, a commonly used natural product for antitumor therapy, is unable to achieve full potential due to poor bioavailability. Based on our previous report of a novel delivery system for curcumin using functionalized single-walled carbon nanotubes by phosphatidylcholine and polyvinylpyrrolidone (SWCNT-Cur), we further evaluated SWCNT-Cur’s performance in vivo and characteristics in vitro. SWCNT-Cur significantly increased the blood concentration of curcumin, up to 18-fold, in mice. And in a murine S180 tumor model, SWCNT-Cur exhibited significantly higher inhibition efficacy on tumor growth and no obvious toxicity in main organs. Moreover, photothermal therapy induced by SWCNT under near-infrared radiation further facilitated SWCNT-Cur to inhibit the tumor growth in vivo. In addition, solvent residue is negligible in SWCNT-Cur formulation, and hydrogen bonding was formed between void carriers and curcumin, as demonstrated by GC chromatograph and IR spectra. Furthermore, experiments of confocal microscopy and spectrofluorometer showed that SWCNT-Cur gave a six-fold higher uptake for curcumin compared to native curcumin in human prostate cancer PC-3 cells. In conclusion, curcumin delivery with functionalized SWCNT is a promising strategy to enhance anticancer activity in vivo by enhancing cell uptake and blood concentration, changing physicochemical properties of curcumin and combining phototherapeutic with chemotherapeutic effects.
关键词: cancer therapy,Curcumin,nanocarriers,single-walled carbon nanotubes,photothermal effect
更新于2025-09-16 10:30:52
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Dual-functional supramolecular nanohybrids of quantum dot/biopolymer/chemotherapeutic drug for bioimaging and killing brain cancer cells in vitro
摘要: Glioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and constructed for the first time quantum dot-biopolymer-drug nanohybrids based on host-guest chemistry for simultaneous bioimaging, targeting, and anti-cancer drug delivery against GBM cells in vitro. ZnS fluorescent quantum dots (ZnS-QDs) were produced using chemically modified polysaccharide, carboxymethylcellulose (CMC), as water-soluble capping ligand and biofunctional layer via a facile one-step eco-friendly aqueous colloidal process at room temperature and physiological pH. These hybrid inorganic-organic nanocolloids (ZnS@CMC) were electrostatically conjugated with doxorubicin (DOX) anti-cancer drug forming innovative supramolecular complexes (ZnS@CMC-DOX) for amalgamating bioimaging and killing cancer cells. These nanoconjugates were characterized regarding their optical and physicochemical properties combined with morphological and structural features. The cytocompatibility was evaluated by MTT assay using healthy and GBM cells. The results showed that ultra-small ZnS-QDs were expertly produced uniform nanocolloids (average size = 3.6 nm). They demonstrated photoluminescence emission within the visible range of spectra. The cell viability results in vitro showed no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. In summary, the novelty of this research relies on using a nanotheranostic strategy for developing ZnS@CMC-DOX nanohybrids with supramolecular vesicle-like structures. They behaved simultaneously as active fluorescent nanoprobes and nanocarriers with modulated drug release for bioimaging and killing malignant glioma cells proving the high potential for applications in cancer nanomedicine.
关键词: Nanocarriers,Cancer nanotheranostic,Nanocolloids,Nanoconjugates,Fluorescent nanoparticles,Nanomedicine,Nanohybrids,Nanoparticles
更新于2025-09-12 10:27:22
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Photoactive Nanocarriers for Controlled Delivery
摘要: Photoactive nanocarriers have emerged as robust and minimally invasive systems for the on-demand delivery of active payloads. The easy manipulation offered by light irradiation as an external stimulus allows precise spatiotemporal control of payload release based on the time, intensity, location, and wavelength of light exposure. Compared to conventional passive delivery systems, photoactive nanocarriers offer the possibility of tailoring the release kinetics of the encapsulated active molecules, which is of considerable clinical relevance for targeted delivery to desired sites of interest. In this progress report, the recent advances in the design and fabrication of photoactive nanoplatforms based on three main modes of mechanisms: photochemical reactions, the photothermal effect, and photosensitization mechanism mediated by reactive oxygen species are highlighted. The combination of these mechanisms provides additional flexibility for the effective delivery of therapeutics and improved synergistic therapeutic effects. Finally, challenges in future perspectives on the development of photoactive nanomaterials and their medical translation are discussed.
关键词: photothermal effects,photosensitization,photochemical reaction,nanocarriers,controlled delivery
更新于2025-09-11 14:15:04
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Functional Polymer Nanocarriers for Photodynamic Therapy
摘要: Photodynamic therapy (PDT) is an appealing therapeutic modality in management of some solid tumors and other diseases for its minimal invasion and non-systemic toxicity. However, the hydrophobicity and non-selectivity of the photosensitizers, inherent serious hypoxia of tumor tissues and limited penetration depth of light restrict PDT further applications in clinic. Functional polymer nanoparticles can be used as a nanocarrier for accurate PDT. Here, we elucidate the mechanism and application of PDT in cancer treatments, and then review some strategies to administer the biodistribution and activation of photosensitizers (PSs) to ameliorate or utilize the tumor hypoxic microenvironment to enhance the photodynamic therapy effect.
关键词: hypoxia,photodynamic therapy,nanocarriers,photosensitizers
更新于2025-09-04 15:30:14