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Selectivity in Photodynamic Action: Higher Activity of Mitochondria Targeting Photosensitizers in Cancer Cells
摘要： Among the pathways for improving the practice of photodynamic therapy of cancer, increasing the selectivity of photodynamic action is an obvious choice. Considering the different characteristics of mitochondria in normal cells and cancer cells, we designed mitochondria targeting photosensitizers. We now demonstrate that mitochondria targeted photosensitizers by TPP-derivatization, are more selective for cancer cells compared to normal cells, presumably due to larger membrane potential of cancer cell mitochondria allowing more efficient accumulation of the photosensitizer.
关键词： organelle targeting,photodynamic action,singlet oxygen,photosensitizers,photodynamic therapy
更新于2025-09-23 15:22:29
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Interventional Photothermal Therapy Enhanced Brachytherapy: A New Strategy to Fight Deep Pancreatic Cancer
摘要： Photothermal–radiotherapy (PT–RT) is an effective strategy for relieving hypoxia-related radiotherapy resistance and inducing tumor-specific cell apoptosis/necrosis. Nevertheless, limited tissue penetration of near-infrared (NIR) laser and the serious side effects of high-dose radiation severely hinder its applications for deep tumors. An interventional photothermal–brachytherapy (IPT–BT) technology is proposed here for the internal site-specific treatment of deep tumors. This technology utilizes a kind of biodegradable honeycomb-like gold nanoparticles (HGNs) acting as both internal photothermal agents and radiosensitizers. A high tumor inhibition rate of 96.6% is achieved in SW1990 orthotopic pancreatic tumor-bearing mice by HGNs-mediated IPT–BT synergistic therapy. Interestingly, this approach effectively causes double-stranded DNA damage and improves the oxygen supply and the penetration of nanoparticles inside the tumor. Therefore, it is believed that this strategy may open up a new avenue for PT–RT synergistic therapy of deep malignant tumors and has a significant impact on the future clinical translation.
关键词： photothermal therapy,pancreatic cancer,biodegradable,interventional,brachytherapy,honeycomb-like gold
更新于2025-09-23 15:22:29
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Enzyme-responsive multifunctional peptide coating of gold nanorods improves tumor targeting and photothermal therapy efficacy
摘要： It is well known that stealth coating effectively extends the circulation lifetime of nanomaterials in blood, which favors systemic delivery but also limits their cellular internalization and in turn prevents efficient tumor-targeting and accumulation. In this study, we address this dilemma by developing an enzyme-responsive zwitterionic stealth peptide coating capable of responding to matrix metalloproteinase-9 (MMP-9) which is overexpressed in tumor microenvironment. The peptide consists of a cell-penetrating Tat sequence, an MMP-9 cleavable sequence, and a zwitterionic antifouling sequence. Using this coating to protect photothermal gold nanorods (AuNRs), we found that responsive AuNRs showed both satisfactory systemic circulation lifetime and significantly enhanced cellular uptake in tumors, resulting in clearly improved photothermal therapeutic efficacy in mouse models.
关键词： Tat peptide,photothermal therapy,gold nanorods,zwitterionic peptide,MMP-9 responsive
更新于2025-09-23 15:22:29
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Decreased phototoxicity of photodynamic therapy by Cx32/Cx26-composed GJIC: A “Good Samaritan” effect
摘要： Background and Objective: Photodynamic therapy (PDT) has been widely used to treat malignant tumors. Our previous studies indicated that connexin (Cx) 32- and Cx26-composed gap junctional intercellular communication (GJIC) could improve the phototoxicity of PDT. However, the role of heterotypic Cx32/Cx26-formed GJIC in PDT phototoxicity is still unknown. Thus, the present study was aimed to investigate the effect of Cx32/Cx26-formed GJIC on PDT efficacy. Methods: CCK8 assay was used to detect cell survival after PDT. Western blot assay was utilized to detect Cx32/Cx26 expression. "Parachute" dye-coupling assay was performed to measure the function of GJ channels. The intracellular Ca2+ concentrations were determined using flow cytometer. ELISA assay was performed to detect the intracellular levels of PGE2 and cAMP. Results: The present study demonstrates there is a Cx32/Cx26-formed GJIC-dependent reduction of phototoxicity when cells were exposure to low concentration of Photofrin. Such a protective action is missing at low cell density due to the lack of GJ coupling. Under high-cell density condition, where there is opportunity for the cells to contact each other and form GJ, suppressing Cx32/Cx26-formed GJIC by either inhibiting the expression of Cx32/Cx26 or pretreating with GJ channel inhibitor augments PDT phototoxicity after cells were treated with at 2.5 mg/ml Photofrin. The above results suggest that at low Photofrin concentration, the presence of Cx32/Cx26-formed GJIC may decrease the phototoxicity of PDT, leading to the insensitivity of malignant cells to PDT treatment. The GJIC-mediated PDT insensitivity was associated with Ca2+ and prostaglandin E2 (PGE2) signaling pathways. Conclusion: The present study provides a cautionary note that for tumors expressing Cx32/Cx26, the presence of Cx32/Cx26-composed GJIC may cause the resistance of tumor cells to PDT. Oppositely, treatment strategies designed to downregulate the expression of Cx32/Cx26 or restrain the function of Cx32/Cx26-mediated GJIC may increase the sensitivity of malignant cell to PDT.
关键词： gap junctional intercellular communication,photodynamic therapy,Cx32/Cx26
更新于2025-09-23 15:22:29
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Polydopamine-Coated Gold Core/Hollow Mesoporous Silica Shell Particles as a Nanoplatform for Multimode Imaging and Photothermal Therapy of Tumors
摘要： It is highly desirable to develop a new hybrid nanoplatform that integrates diagnosis and treatment elements for effective theranostics of tumors. Herein, we have skillfully designed a nanoplatform of polydopamine (PDA)-coated and perfluorohexane (PFH)-filled gold core/hollow mesoporous silica shell (Au@mSiO2-PFH-PDA, ASPP for short) particles for photoacoustic (PA)/ultrasound (US)/computed tomography (CT)/thermal imaging and photothermal therapy (PTT) of tumors. In this work, we first synthesized Au seed particles with a diameter of 15.8 nm using a sodium citrate reduction method, and coated Au seeds with polyvinylpyrrolidone for further growth of solid silica shell/mesoporous silica shell onto the Au seeds. After treatment via selective etching to remove solid silica shell, amination of surface of the particles, and filling of PFH into the internal cavity of the spheres with a diameter of 182.1 nm, PDA coating was performed to render the particles with an external shell thickness of 15.1 nm. The formed hybrid particles with a size of 212.2 nm are colloidally stable and exhibit good cytocompatibility, and display excellent PA/US/CT/thermal imaging property due to the co-presence of PDA, PFH, and Au nanoparticles. Furthermore, the PDA coating renders the platform with a photothermal conversion efficiency of 61.2%, enabling effective photothermal ablation of cancer cells in vitro and a xenografted 4T1 tumor model in vivo under irradiation with an 808 nm laser. More importantly, in the primary 4T1 tumor model, intratumoral injection of the ASPP and irradiation with an 808 nm laser can also completely inhibit the occurrence lung metastasis induced by the 4T1 tumor. The as-prepared hybrid nanoplatform may hold a great promise to be adopted for multimode imaging and PTT of tumors and inhibition of tumor metastasis.
关键词： Tumor metastasis inhibition,Multimode imaging,Photothermal therapy,Polydopamine NPs,Hollow mesoporous silica,Surface modification
更新于2025-09-23 15:22:29
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Layer-by-layer Modification of Magnetic Graphene Oxide by Chitosan and Sodium Alginate with Enhanced Dispersibility for Targeted Drug Delivery and Photothermal Therapy
摘要： In this work, graphene oxide nanosheets loaded by magnetic iron oxide nanoparticles (mGO) was synthesized and the technique of layer-by-layer (LbL) self-assembly was utilized in the successful production of chitosan/ sodium alginate functionalized mGO naocomposites for use in targeted anti-cancer drug delivery and photothermal therapy. The mGO-CS/SA nanocomposites had a diameter of ~0.5 μm and a thickness of 40-60 nm with superparamagnetic behavior. The modified nanocomposites exhibited a decrease in agglomeration and an increase in stability in biological solution following stability tests. Meanwhile, the nonspecific protein adsorption was strongly suppressed after the modification. The mGO-CS/SA nanocomposites were loaded with doxorubicin hydrochloride (DOX) via π- π stacking and electrostatic attraction with a high drug loading amount (121%, w/w). The DOX-loaded nanocomposites (mGO-CS/SA-DOX) showed improvements in function including enhanced dispersion and noticeable pH-sensitive drug release behavior. Cellular studies denoted magnetically targeted cellular uptake characteristics and excellent photothermal effect of mGO-CS/SA, as well as concentration-dependent cytotoxicity of mGO-CS/SA-DOX. Therefore the functionalization of mGO using chitosan and sodium alginate would be beneficial in biomedical applications.
关键词： magnetic nanocomposite,Layer-by-layer,Graphene oxide,photothermal therapy,drug delivery
更新于2025-09-23 15:22:29
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Extracellular vesicles based self-grown gold nanopopcorn for combinatorial chemo-photothermal therapy
摘要： Here, we generated a popcorn-like gold nanostructure exploiting extracellular vesicles (EVs). EVs can first serve as the vehicle for chemotherapeutic drug doxorubicin (DOX). Taking advantages of EVs, gold nanoparticles can be then self-grown surrounding the EVs, assembling into popcorn-like nanostructure. The formulated nanopopcorn, consisting of self-grown gold nanoparticles and EVs encapsulated with DOX, retained the photothermal transduction from gold nanoparticle assemblies and cytotoxicity of DOX. Under external near infrared irradiation, gold nanopopcorn can produce hyperthermia to induce tumor ablation and trigger drug release, achieving combinatorial chemo-photothermal therapy. The nanoplatform demonstrated improved cellular internalization, controlled drug release, enhanced antitumor efficacy with tumor inhibitory rate up to 98.6% and reduced side effects. Our design of popcorn-like nanostructure will contribute a novel modality for facile and green synthesis of complex metal nanostructures exploiting natural properties of EVs for combinational therapy.
关键词： photothermal therapy,self-growth,gold nanopopcorn,chemotherapy,extracellular vesicles
更新于2025-09-23 15:22:29
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Ultrastructural and optical characteristics of cancer cells treated by a nanotechnology based chemo-photothermal therapy method
摘要： The current chemotherapy method demonstrates the need for improvement in terms of efficacy and safety. Given the beneficiary effect of heat in combination with chemotherapy, the purpose of this study is to develop a multifunctional nanoplatform by co-incorporating gold nanoparticles (AuNPs) as photothermal agent and cisplatin as anticancer drug into alginate hydrogel (named as ACA) to enable concurrent thermo-chemotherapy. The in vitro cytotoxicity experiment showed that the as-developed nanocomplex was able to induce greater cytotoxicity in KB human nasopharyngeal cancer cells compared to free cisplatin at the same concentration. Moreover, the interaction of ACA and laser irradiation acted synergistically and resulted in higher cell death rate compared to separate application of photothermal therapy and chemotherapy. The micrograph of KB cells also revealed that ACA was able to selectively accumulate into the mitochondria, so that laser irradiation of KB cells pre-treated with ACA resulted in intensive morphological damages such as plasma membrane disruption, chromatin condensation, autophagic vacuoles formation and organelle degeneration. Moreover, the sign and magnitude of altered optical nonlinear refractive index measured by Z-scan technique was shown to be significantly in cells exposed to irradiation. Consequently, the nanocomplex developed herein could be a promising platform to combine photothermal therapy and chemotherapy effectively, thereby achieving synergistic therapeutic outcome.
关键词： Gold nanoparticles,Cisplatin,Chemotherapy,Photothermal therapy,Thermo-chemotherapy
更新于2025-09-23 15:22:29
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Antimicrobial efficacy of photodynamic therapy on dental implant surfaces: A systematic review of in vitro studies
摘要： Background: To systematically review the literature regarding the antimicrobial effects of photodynamic therapy (PDT) on the multi-bacterial species and the possible surface alterations of the dental implants as a result of PDT. Methods: The addressed focused question was: “Does PDT show antimicrobial efficacy against multi-bacterial species colonization and result in surface alteration on dental implants?” Electronic databases including MEDLINE and EMBASE up to and including December 2018 were searched. Results: Seven studies were included. Two studies used a total of 110 titanium dental implants, while 1 study included a total of 72 zirconia dental implants. Three studies investigated the antimicrobial PDT effects on titanium discs, while 1 study used titanium plates with germanium prisms. All in-vitro studies used diode laser. Energy fluence was reported only in 2 studies. Power output and density were 100 milliwatts (mW) and 150 mW cm-2, respectively. All in-vitro studies reported the multibacterial species outcomes after the application of antimicrobial PDT. All studies showed a significant reduction in the bacterial load. Only two studies reported the outcomes of microstructural changes on the titanium surface, in which both studies did not report any significant alterations on the titanium implants or discs with the application of PDT. Conclusion: This systematic review demonstrated significant reduction in the bacterial load but inconclusive findings regarding structural alterations on the titanium surface with the use of PDT. The results of this review should be considered preliminary and further in-vitro studies with standardized laser parameters are needed to obtain strong conclusions.
关键词： systematic review,titanium surface,dental implants,photodynamic therapy,bacterial load
更新于2025-09-23 15:22:29
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Smart NIR-Light-Mediated Nanotherapeutic Agents for Enhancing Tumor Accumulation and Overcoming Hypoxia in Synergistic Cancer Therapy
摘要： The efficacy of photodynamic therapy (PDT) still shows limited success in clinical application due to hypoxia in the solid tumor, low tumor accumulation and limited light penetration depth of photosensitizers (PS). The previously reported MnO2-based nanotherapeutic agents always required intratumoral injection or complex targeting modification process to improve the therapeutic efficacy. Herein, new MnO2-based nanotherapeutic agents (honeycomb MnO2/IR780/BSA nanoparticles, HMIB NPs) are designed and prepared to achieve excellent phototherapeutic performance characterized by NIR-light-mediation, deep diffusion via TME response and O2 self-supply. The ex vivo and in vivo NIR fluorescence imaging results demonstrate that the honeycomb nanostructure of HMIB NPs facilitates the high tumor accumulation of hydrophobic IR780 via enhanced permeability and retention (EPR) effect after intravenous injection. The immunofluorescence results demonstrate that the TME response of HMIB NPs not only provides O2 for relieving hypoxia but also reduces size for improving deep intratumoral diffusion. As a result, under the synergy of NIR fluorescence imaging, photothermal effect and PDT of IR780 with TME responsive size-change and O2 self-supply of honeycomb MnO2, the HMIB NPs have achieved all-in-one NIR fluorescence and photothermal dual-model imaging guided synergistic PDT/PTT under a single-wavelength NIR light irradiation.
关键词： nanotherapeutic agents,tumor microenvironment responsive degradation,photodynamic therapy,hypoxia,honeycomb manganese dioxide
更新于2025-09-23 15:22:29