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Gold-tagged Polymeric Nanoparticles with Spatially Controlled Composition for Enhanced Detectability in Biological Environments
摘要： Organic nanoparticles offer the advantage of high biocompatibility for biomedical applications but suffer frequently from poor visibility in biological environments. While fluorescent-labeling is convenient and allows for fast and extensive histological analysis, fluorescence imaging and quantitative analysis are limited by low resolution and significantly hindered by tissue auto-fluorescence. Labeling of polymeric nanoparticles with an additional gold tag would allow for high resolution imaging via transmission electron microscopy (TEM) and for quantification of particles by inductively coupled plasma optical emission spectrometry (ICP-OES). However, spatially uncontrolled gold-tagging can cause significant fluorescence quenching. To overcome this restraint, 2.2 nm gold nanoparticles were introduced at the interface between the hydrophobic fluorophore-loaded core and the hydrophilic shell of polymeric nanoparticles. Due to the small size of gold labels and the spatially controlled stratified composition of hybrid nanoparticles, fluorescence quenching by gold tags was minimized to 15.1%, allowing for concomitant detection of both labels via optical microscopy after enhancement of the gold tags. Multilayered hybrid nanoparticles exhibited outstanding detectability by transmission electron microscopy, even without additional sample staining. Furthermore, they were capable of producing remarkable image contrast inside cells after gold or silver enhancement. The interfacial gold layer increased the hydrodynamic particle size only marginally from 71.8 to 89.5 nm and had no negative impact on biocompatibility in vitro. The gold content (0.75% m/m) is sufficiently high for future quantification in tissues after systemic administration. With their clean-cut structure and superior detectability, multilayered hybrid nanoparticles constitute an outstanding blueprint and a precious tool for the development of nanomedicines.
关键词： gold,polymeric nanoparticles,hybrid,TEM,PLGA,contrast agent
更新于2025-11-21 11:24:58
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Hyaluronic acid functionalized nanoparticles loaded with IR780 and DOX for cancer chemo-photothermal therapy
摘要： IR780 is a near infrared (NIR) dye with a huge potential to be applied in cancer phototherapy and imaging. However, IR780 poor water solubility and acute cytotoxicity limit its direct use in cancer theragnostic. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was used, for the first time, in the preparation of polymeric nanoparticles (HPN) encapsulating IR780 aimed to be applied in breast cancer therapy. Furthermore, HPN co-encapsulating IR780 and Doxorubicin (DOX) were also produced in order to further enhance the therapeutic effectiveness of this nanoformulation. The results revealed that HPN were able to successfully encapsulate IR780 (IR-HPN) and the IR780-DOX combination (IR/DOX-HPN). Furthermore, the encapsulation of IR780 in HPN improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential, as well as its cytocompatibility. The 2D in vitro cell uptake studies demonstrated that the nanostructures displayed a higher internalization by breast cancer cells than by normal cells. In addition, the assays performed in 3D in vitro models of breast cancer revealed that HPN can penetrate into spheroids. Furthermore, the 3D in vitro studies also demonstrated that the combined application of IR-HPN and NIR light was unable to induce cytotoxicity on spheroids. In contrast, IR/DOX-HPN produced a decrease on spheroids cells’ viability, and their combination with NIR light induced an even stronger therapeutic effect, thus revealing the potential of these nanoparticles for cancer chemo-phototherapy.
关键词： Cancer,Polymeric Nanoparticles,Chemotherapy,IR780,Photothermal therapy,Doxorubicin
更新于2025-11-21 11:08:12
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How to unravel the chemical structure and component localization of individual drug-loaded polymeric nanoparticles by using tapping AFM-IR
摘要： AFM-IR is a photothermal technique that combines AFM and infrared (IR) spectroscopy to unambiguously identify the chemical composition of a sample with tens of nanometer spatial resolution. So far, it has been successfully used in contact mode in a variety of applications. However, the contact mode is unsuitable for soft or loosely adhesive samples such as polymeric nanoparticles (NPs) of less than 200 nm of wide interest for biomedical applications. We describe here the theoretical basis of the innovative tapping AFM-IR mode that can address novel challenges in imaging and chemical mapping. The new method enables gaining information not only on NP morphology and composition, but also reveals drug location and core–shell structures. Whereas up to now the locations of NP components could only be hypothesized, tapping AFM-IR allows accurately visualizing both the location of the NPs’ shells and that of the incorporated drug, pipemidic acid. The preferential accumulation of the drug in the NPs’ top layers was proved, despite its low concentration (<1 wt%). These studies pave the way towards the use of tapping AFM-IR as a powerful tool to control the quality of NP formulations based on individual NP detection and component quantification.
关键词： tapping mode,chemical mapping,core–shell structure,drug localization,polymeric nanoparticles,AFM-IR
更新于2025-11-14 15:18:02
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Precisely Tuning Photothermal and Photodynamic Effects of Polymeric Nanoparticles by Controlled Copolymerization
摘要： In the past decades, cancer has become a major threat to the health of human being. Comparing to the conventional cancer therapy methods, such as surgery, chemotherapy, radiotherapy, and electrotherapy, photothermal and photodynamic therapy has attracted considerable interest because of their noninvasiveness, effectiveness, and negligible side effects. Photothermal therapy (PTT) can induce hyperthermia in tumor sites locally and ablate the tumor using the heat from photothermal nano-agents irradiated by the near-infrared (NIR) laser. However, hyperthermia can cause overexpression of heat shock proteins (HSPs), leading to inadequate apoptosis and tumor recurrence, thereby weakening the PTT effect. Thus, strong PTT-only nano-agents may not be the optimal choice for cancer therapy. Photodynamic therapy (PDT) can induce apoptosis and necrosis of tumor cells, mainly relying on highly toxic singlet oxygen (1O2) generated from photosensitizing nano-agents upon NIR laser irradiation. Under normoxic tumor sites, 1O2 can destroy cells and blood vessels to damage the tumor. Thus, nano-agents with moderate photothermal effect and strong photodynamic effect may be the optimal choice for killing cells and blood vessels under these sites. On the other side, the hypoxia microenvironment also formed inside the dense tumor, which limits the effect of PDT. When PDT was combined with PTT, the high hyperthermia can increase the oxygen content in a microvessel inside the dense tumor to ease the tumor hypoxic situation, which is beneficial to the PDT efficiency. Therefore, a phototherapy nanoplatform with strong photothermal and photodynamic effects may be the optimal solution to erase cancer cells inside the hypoxic dense tumor. Obviously, different conditions need different nano-agents with different functions, which requires precisely tuning of photothermal and photodynamic effects.
关键词： polymeric nanoparticles,photothermal/photodynamic effect,copolymerization,tellurium,pyrrole
更新于2025-09-23 15:21:01
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Precisely Tuning Photothermal and Photodynamic Effects of Polymeric Nanoparticles by Controlled Copolymerization
摘要： In the past decades, cancer has become a major threat to the health of human being. Comparing to the conventional cancer therapy methods, such as surgery, chemotherapy, radiotherapy, and electrotherapy, photothermal and photodynamic therapy has attracted considerable interest because of their noninvasiveness, effectiveness, and negligible side effects. Photothermal therapy (PTT) can induce hyperthermia in tumor sites locally and ablate the tumor using the heat from photothermal nano-agents irradiated by the near-infrared (NIR) laser. However, hyperthermia can cause overexpression of heat shock proteins (HSPs), leading to inadequate apoptosis and tumor recurrence, thereby weakening the PTT effect. Thus, strong PTT-only nano-agents may not be the optimal choice for cancer therapy. Photodynamic therapy (PDT) can induce apoptosis and necrosis of tumor cells, mainly relying on highly toxic singlet oxygen (1O2) generated from photosensitizing nano-agents upon NIR laser irradiation. Under normoxic tumor sites, 1O2 can destroy cells and blood vessels to damage the tumor. Thus, nano-agents with moderate photothermal effect and strong photodynamic effect may be the optimal choice for killing cells and blood vessels under these sites. On the other side, the hypoxia microenvironment also formed inside the dense tumor, which limits the effect of PDT. When PDT was combined with PTT, the high hyperthermia can increase the oxygen content in a microvessel inside the dense tumor to ease the tumor hypoxic situation, which is beneficial to the PDT efficiency. Therefore, a phototherapy nanoplatform with strong photothermal and photodynamic effects may be the optimal solution to erase cancer cells inside the hypoxic dense tumor. Obviously, different conditions need different nano-agents with different functions, which requires precisely tuning of photothermal and photodynamic effects.
关键词： polymeric nanoparticles,photothermal/photodynamic effect,copolymerization,tellurium,pyrrole
更新于2025-09-23 15:21:01
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Exploiting Wavelength Orthogonality for Successive Photoinduced Polymerization-Induced Self-Assembly and Photo-Crosslinking
摘要： We report a facile benchtop process for the synthesis of cross-linked polymeric nanoparticles by exploiting wavelength-selective photochemistry to perform orthogonal photoinduced polymerization-induced self-assembly (Photo-PISA) and photo-crosslinking processes. We first established that the water-soluble photocatalyst, zinc meso-tetra(N-methyl-4-pyridyl) porphine tetrachloride (ZnTMPyP) could activate the aqueous PET-RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA). This photo-PISA process could be conducted under low energy red light (λ max = 595 nm, 10.2 mW/cm2) and without deoxygenation due to the action of the singlet oxygen quencher, biotin (vitamin B7), which allowed for the synthesis of a range of nanoparticle morphologies (spheres, worms, and vesicles) directly in 96-well plates. To perform wavelength selective nanoparticle cross-linking, we added the photoresponsive monomer, 7-[4-(trifluoromethyl)coumarin] methacrylamide (TCMAm) as a comonomer without inhibiting the evolution of the nanoparticle morphology. Importantly, under red light, exclusive activation of the photo-PISA process occurs, with no evidence of TCMAm dimerization under these conditions. Subsequent switching to a UV source (λ max = 365 nm, 10.2 mW/cm2) resulted in rapid cross-linking of the polymer chains, allowing for retention of the nanoparticle morphology in organic solvents. This facile synthesis of cross-linked spheres, worms, and vesicles demonstrates the utility of orthogonal light-mediated chemistry for performing decoupled wavelength selective chemical processes.
关键词： photoinduced polymerization-induced self-assembly,wavelength orthogonality,polymeric nanoparticles,photo-crosslinking,PET-RAFT polymerization
更新于2025-09-23 15:21:01
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Cisplatin-Loaded Polymeric Micelles with Aggregation-Induced Emission Feature for Cellular Imaging and Chemotherapy
摘要： Imaging-guided disease theranostic nanoplatforms based on polymeric micelles have drawn a broad attention because of their clear visualization, reduced systemic toxicity, enhanced utilization of drugs, and suppressed chemoresistance of tumors, which makes them possess potential application for cancer therapy. Herein, we synthesized a polymeric nanoparticles (Poly (MAD-alt-OCE)-PTZ-PEG) with novel aggregation-induced emission (AIE) characteristic based on cheap commercial polymer by the simple and environmental method. These Poly(MAD-alt-OCE)-PTZ-PEG nanoparticles (NPs) show excellent biocompatibility and fluorescence property, which makes them huge application potential for cellular imaging. Furthermore, the antitumor drug cisplatin Pt(IV) can be loaded efficiently onto the surface of Poly(MAD-alt-OCE)-PTZ-PEG NPs due to the existence of abundant carboxyl groups on the NPs surface. The well-controlled Pt(IV)-loaded yield and great acid-responsive drug release of these polymeric micelles enhance cytotoxicity against cancer cells in vitro. Given the cheap raw materials, eco-friendly method, excellent AIE property, efficient antitumor drug delivery and pH-controlled drug release, these polymeric NPs would be a potential candidate for cancer diagnosis and therapy in the future.
关键词： Aggregation-induced emission,Drug delivery,Cellular imaging,Polymeric nanoparticles
更新于2025-09-23 15:19:57
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Photoactivatable Prodrug-Backboned Polymeric Nanoparticles for Efficient Light-Controlled Gene Delivery and Synergistic Treatment of Platinum-Resistant Ovarian Cancer
摘要： Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, lacking of suitable co-delivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. Herein, we developed a photoactivatable Pt(IV) prodrug-backboned polymeric nanoparticles system (CNPPtCP/si(c-fos)) for light-controlled si(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNAi on platinum-resistant ovarian cancer (PROC). Upon blue light irradiation (430 nm), CNPPtCP/si(c-fos) could generate oxygen-independent N3? with mild oxidation energy for efficient endo/lysosomal escape through N3?-assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt(IV) prodrug activation, CNPPtCP/si(c-fos) would be disassociated to release active Pt(II) and unpack si(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNPPtCP/si(c-fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug co-delivery tactics for treatment of various hard-to-tackle cancers.
关键词： N3?-assisted photochemical internalization,photoactivatable polymeric nanoparticles,gene delivery,platinum-resistant ovarian cancer,photoactivated chemotherapy
更新于2025-09-19 17:13:59
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Corea??shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions
摘要： Background: Biodistribution of photosensitizer (PS) in photodynamic therapy (PDT) can be assessed by fluorescence imaging that visualizes the accumulation of PS in malignant tissue prior to PDT. At the same time, excitation of the PS during an assessment of its biodistribution results in premature photobleaching and can cause toxicity to healthy tissues. Combination of PS with a separate fluorescent moiety, which can be excited apart from PS activation, provides a possibility for fluorescence imaging (FI) guided delivery of PS to cancer site, followed by PDT.
关键词： Polymeric nanoparticles,Poly-N-isopropylacrylamide,Electronic excitation energy transfer,Photodynamic therapy,Short wave infrared fluorescence bioimaging
更新于2025-09-16 10:30:52
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Reversibly Photoswitchable Dual-Color Fluorescence and Controlled Release Properties of Polymeric Nanoparticles
摘要： Here, we report a novel polymeric nanoparticle prepared by the self-assembly of amphiphilic copolymers containing a ?uorescent naphthalimide (NAPH) and a photochromic spiropyran (SP), which possesses reversibly photoswitchable dual-color ?uorescence and controlled release properties. The amphiphilic copolymers were synthesized by incorporating NAPH and SP into methyl ether poly(ethylene glycol)-poly(β-amino esters) (MPEG-PAE) via quaternization. The nanoparticles would change between yellow and purple reversibly upon UV and visible light irradiation because of the photoisomerization between SP and merocyanine (MC). The corresponding ?uorescence would be switched between green and orange-red reversibly upon blue light excitation through the ?uorescence resonance energy transfer from the excited NAPH to the photoisomerized MC. Meanwhile, the prepared spherical nanoparticles could be swollen under UV irradiation as the hydrophobic SP isomerized to hydrophilic MC; the nanoparticles could also be swollen under acidic conditions because of the protonation of the amino groups of PAE. Upon UV light irradiation and acidic stimulation, the cargoes, hydrophobic Coumarin 102, encapsulated in the nanoparticles would be released. The prepared nanoparticles, which exhibit not only excellent reversible dual-color ?uorescence properties but also prominent controlled release performance, will open up new possibilities for the combined application of ?uorescence imaging and controlled release.
关键词： naphthalimide,Coumarin 102,spiropyran,polymeric nanoparticles,photoswitchable,amphiphilic copolymers,acidic conditions,quaternization,self-assembly,FRET,UV/vis light irradiation,dual-color ?uorescence,MPEG-PAE,controlled release
更新于2025-09-11 14:15:04