Mitochondria-targeted Photosensitizers Research Articles

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Imaging/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Dual nanoparticle immunostimulant hydrogel for synergistic combating “Cold” tumor

The immunosuppressive tumor microenvironment (TME) in “cold” triple-negative breast cancer (TNBC) leads to resistance to current immunotherapies. Here, we designed an in-situ hydrogel reservoir to deliver two types of nanoparticles (NPs) targeting 4T1 tumor cells and tumor-associated macrophages (TAMs) for cancer cell elimination and reversal of the immunosuppressive TME. The 4T1 tumor cell-targeted NPs could specifically deliver the mitochondria-targeted photosensitizer and catalase into 4T1 tumor cells to execute an enhanced photodynamic therapy and induce immunogenic cell death. The TAMs-targeted NPs delivered the stimulator of interferon genes (STING) agonist into macrophages to activate the STING pathway, triggering a type I interferon-driven innate immune response that induces a shift to a “hot” T cell-inflamed TME. This local synergistic therapy could effectively stimulate dendritic cell activation and the continuous T-cell infiltration, thereby reprograming the immunosuppressive TME, reinvigorating a powerful anti-tumor immune response and inhibiting tumor growth and metastasis in TNBC tumor model. In addition, this study combined with immune checkpoint blockade further achieves reinforced therapeutic outcome against “cold” tumor, providing a promising hydrogel-mediated platform for treatment of TNBC.

"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Mitochondrial-Targeted CS@KET/P780 Nanoplatform for Site-Specific Delivery and High-Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria-targeted chemo-photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria-targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor-targeted and subsequently pH-responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET-induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer-term antitumor response by releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity.

Biotin-conjugated Ru(II) complexes with AIE characteristics as mitochondria-targeted photosensitizers for enhancing photodynamic therapy by disrupting cellular redox balance

The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm−2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An invivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.Graphical

Highly Efficient Photodynamic Therapy with Mitochondria-Targeting Aggregation-Induced Emission Photosensitizer for Retinoblastoma.

Retinoblastoma (RB) is an aggressive eye cancer in infancy and childhood, lethal by metastasis if left untreated. Currently, the survival rate and the chance of saving vision depend on the severity of the disease. In this work, a highly efficient photodynamic ophthalmic therapy for RB is reported by employing an isoquinolinium-based aggregation-induced-emission (AIE) photosensitizer (PS) TPE-IQ-2O for photodynamic inactivation (PDI). TPE-IQ-2O is an efficient mitochondria-targeting photosensitizer as an efficient guided photodynamic therapy (PDT) agent against cancer cells. Maximizing cancer-selectively damage to tumors with minimized side effects on normal tissue is essential for effective anticancer PDT and provides long-lasting protection against metastasis. In addition, TPE-IQ-2O can effectively reduce the degree of tissue inflammation by inhibiting the expression of related inflammatory factors. TPE-IQ-2O also exhibits excellent biocompatibility with a neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications in the treatment of RB.

Morphological Transformation and In Situ Polymerization of Caspase-3 Responsive Diacetylene-Containing Lipidated Peptide Amphiphile for Self-Amplified Cooperative Antitumor Therapy.

In order to artificially regulate cell behaviors, intracellular polymerization as an emerging chemical technique has attracted much attention. Yet, it is still a challenge to achieve effective intracellular polymerization to conquer tumors in the complex cellular environment. Herein, this work develops a tumor-targeting and caspase-3 responsive nanoparticle composed of a diacetylene-containing lipidated peptide amphiphile and mitochondria-targeting photosensitizer (C3), which undergoes nanoparticle-to-nanofiber transformation and efficient in situ polymerization triggered by photodynamic treatment and activation of caspase-3. The locational nanofibers on the mitochondria membranes lead to mitochondrial reactive oxygen species (mtROS) burst and self-amplified circulation, offering persistent high oxidative stress to induce cell apoptosis. This study provides a strategy for greatly enhanced antitumor therapeutic efficacy through mtROS burst and self-amplified circulation induced by intracellular transformation and in situ polymerization.

Mitochondria-targeted photosensitizer based nanoplatform loading glutathione inhibitor for enhanced breast cancer photodynamic therapy

Photodynamic therapy (PDT) is an approved photoactivated technique that has been widely used for anti-tumor therapy through the generation of excessive ROS. However, the poor water solubility and targeting ability of photosensitizer and ROS depleting by high concentrations of glutathione (GSH) in the tumor microenvironment will limit the efficiency of PDT and synergistic therapy. Herein, we report a mitochondria targeted heterodimeric photosensitizer (TPP-TK-PPa) that can form co-delivery nanoplatform together with DSPE-PEG2000 and GSH-depleting agent DEM through the self-assembly. The TPP-TK-PPa/DEM NPs reveals excellent mitochondrial targeting ability and can efficiently deliver the therapeutic agents to tumor cells and release them into the mitochondria in an ROS-responsive manner. Additionally, The TPP-TK-PPa/DEM NPs can induce in situ production of ROS during PDT and reduce ROS consumption by decreasing intracellular GSH levels, which is attributed to the progressive release of DEM after cellular internalization. In addition, generation of ROS during PDT leads to distinct changes in mitochondrial membrane potential and morphology, which ultimately leads to apoptosis. More importantly, the in vitro antitumor activity results demonstrate that TPP-TK-PPa/DEM NPs showed remarkable phototoxicity and the IC50 values of TPP-TK-PPa/DEM NPs in MDA-MB-231 breast cancer cells was as low as 250 nM after PDT. This work provides a strategy for the development of photosensitizers with specific organelle targeting ability, which is of great importance for precise and effective PDT.

NRNC-8, a novel mitochondria-immobilization superoxide radical generator for photodynamic therapy

Mitochondria play an important role in carcinogenesis, and alterations in mitochondrial activity are frequently associated with cancer formation. Mitochondria have become attractive targets for cancer therapy, with mitochondria-targeted photodynamic therapy (PDT) being one of the most prominent fields. However, significant limitations remain, such as low spectroscopic absorption, short photosensitizer absorption wavelengths, and organelle targeting stability deterioration during phototherapy. In this work, we synthesized an Aza-Nile red-structured near-infrared photosensitizer NRNC-8 based on side-chain engineering for the first time. NRNC-8 can be successfully immobilized on mitochondria in a reaction-free way by linking C8 alkyl chain on the N atom. This reaction-free immobilization approach efficiently prevents irreversible damage to mitochondrial structure and potential effects on mitochondrial function, as well as photosensitizer leaking from mitochondria during phototherapy. Superoxide anion (O2•-) can be created efficiently under red LED irradiation, which directly damages mitochondria and causes cell death, boosting PDT efficiency. A series of studies demonstrated the great potential of NRNC-8 dyes as efficient mitochondria-targeted imaging-guided photodynamic therapy agents, further highlighting the potential value of the “reaction-free mitochondrion-immobilized” strategy in the design of mitochondria-targeted photosensitizers for more efficient photodynamic therapy.

Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM).

One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase patient survival, it is necessary to cleanse the adjacent tissue from GBM infiltrates. This requires an innovative local approach. One such approach is that of photodynamic therapy (PDT) which uses specific light-sensitizing agents called photosensitizers. Here, we show that tetramethylrhodamine methyl ester (TMRM), which has been used to asses mitochondrial potential, can be used as a photosensitizer to target GBM cells. Primary patient-derived GBM cell lines were used, including those specifically isolated from the infiltrative edge. PDT with TMRM using low-intensity green light induced mitochondrial damage, an irreversible drop in mitochondrial membrane potential and led to GBM cell death. Moreover, delayed photoactivation after TMRM loading selectively killed GBM cells but not cultured rat astrocytes. The efficacy of TMRM-PDT in certain GBM cell lines may be potentiated by adenylate cyclase activator NKH477. Together, these findings identify TMRM as a prototypical mitochondrially targeted photosensitizer with beneficial features which may be suitable for preclinical and clinical translation.

Hyaluronic Acid Coated Liposomes Co-Delivery of Natural Cyclic Peptide RA-XII and Mitochondrial Targeted Photosensitizer for Highly Selective Precise Combined Treatment of Colon Cancer

BackgroundNatural cyclopeptide RA-XII, isolated from Rubia yunnanensis, is a promising chemotherapeutic agent for colon cancer. The photosensitizer protoporphyrin-IX attached with triphenylphosphonium (TPP) could possess mitochondria targeting capacity and exert photodynamic therapy (PDT) by inducing oxidizing damage to the mitochondria and cell apoptosis eventually. In this work, pH-sensitive liposomes were constructed to simultaneously deliver RA-XII as a chemotherapeutic drug and modified porphyrin as a mitochondria-targeting photosensitizer to treat colon cancer, and verified its mechanism of action and antitumor therapeutic efficacy.MethodsThe colon cancer targeting liposome nanoparticle RA/TPPP-Lip was synthesized using thin film hydration. The therapeutic effect and targeting ability of RA/TPPP-Lip was investigated in vitro. And use HCT116 cell allogeneic subcutaneous transplantation tumor model to investigate the anti-tumor and targeting effects of RA/TPPP-Lip in vivo.ResultsRA/TPPP-Lip gained the targeting ability through surface-modified HA to increase the accumulation of RA-XII and TPPP in colon cancer cells. A series of in vitro experimental results showed that TPPP produced cytotoxic ROS under laser irradiation to directly damage cell mitochondria and played a combined role with RA-XII, making RA/TPPP-Lip the best colon cancer cell growth inhibitory effect. Furthermore, in vivo antitumor experiments showed that the RA/TPPP-Lip substantially accumulated at the tumor site and efficiently repressed tumor growth in nude mice.ConclusionWe have successfully designed a new cancer-targeted nanomedicine platform (RA/TPPP-Lip) for the collaborative treatment of colon cancer, which can achieve the targeted continuous release of multiple therapeutic drugs. This work provides a new strategy for precise combination therapy, which may promote the further development of collaborative cancer treatment platforms.

Cyclometalated Iridium(III) Complexes as Mitochondria-targeting Photosensitizers against Cisplatin-resistant Cells.

Four iridium (III) complexes Ir1-Ir4 were synthesized and characterized. Possessing high singlet oxygen production ability and specific mitochondria-localization, Ir1 was developed as a mitochondria-targeting photosensitizer. Ir1 exhibited strong phototoxicity against cancer cell line A549 and its corresponding cisplatin-resistant one A549R. In contrast, Ir1 showed low cytotoxicity toward normal cell HLF. This selectivity resulted from the different uptake amount. With 405 nm irradiation, Ir1 induced mitochondria-mediated cell death in A549R cells, achieving the overcome of drug-resistant.

Self-Assembly of Mitochondria-Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia.

The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria-targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self-assemble into spherical micelles directed to mitochondria. Self-assembly of the photosensitizer resulted in a higher photostability by preventing free rotation of the indoline ring of the indocyanine moiety. The mitochondria targeting capability of the photosensitizer allowed it to utilize intramitochondrial oxygen. We found that the mitochondria-targeted photosensitizer localized to mitochondria and induced apoptosis of cancer cells both normoxic and hypoxic conditions through generation of ROS. The micellar self-assemblies of the photosensitizer were further confirmed to selectively localize to tumor tissues in a xenograft tumor mouse model through passive targeting and showed efficient tumor growth inhibition.

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy.

The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches.

A pH-Activatable nanoparticle for dual-stage precisely mitochondria-targeted photodynamic anticancer therapy

Mitochondria-targeted photodynamic therapy (PDT) has emerged as one of the most efficient antitumor strategies. However, the therapeutic outcome of mitochondria-targeted PDT nanocarriers has been hampered by its poor capability of endosome escape and always-ON mode which induces normal tissue damage. To tackle these limitations, herein a novel pH-activatable nanoparticle is developed with dual-stage targeting capacity of early endosome and mitochondria for exponential activation of fluorescent signals and photodynamic efficacy. This nanoparticle is composed of pH-responsive mPEG-b-PDPA-Cy7.5 fluorescent copolymer and mitochondria-targeted photosensitizer (TPPa). The TPPa-encapsulated nanoparticles (M-TPPa) exhibit 111- and 151-fold enhancement in fluorescent signal and singlet oxygen generation (SOG) on encounting acidic pH environment, respectively. The M-TPPa can be quickly endocytosed by cancer cells and immediately dissociate at acidic early endosome to activate fluorescent signals and photoactivity. Subsequently, the activated TPPa quickly translocates from early endosome to mitochondria. Under laser irradiation, singlet oxygen could be generated in mitochondria, inducing intrinsic apoptosis in human HO8910 ovarian cancer cells. M-TPPa also exhibits high tumor imaging contrast and remarkable inhibition on tumor progression without obvious toxicity in HO8910-tumor bearing mice. Therefore, the rationally designed nanoparticles, with precise dual-targeting of distinct organelles and theranostic signal amplification, provides a promising strategy for efficient cancer treatment.

Dual-selective photodynamic therapy with a mitochondria-targeted photosensitizer and fiber optic cannula for malignant brain tumors.

Among brain tumors, glioblastoma multiforme (GBM) is the most common and aggressive form (WHO grade IV) with a median survival of only 14.6 months in adults. Photodynamic therapy (PDT) is a combination of a photosensitizer (PS), light and molecular oxygen, and considered a promising treatment for GBM. Therapeutic outcomes of PDT rely on ROS generation in a tumor microenvironment, which can be controlled with dual selectivity by localization of the photosensitizer and confinement of light to the targeted tumor microenvironment. We previously demonstrated the photodynamic anticancer efficacy of mitochondrial-targeted photosensitizer-loaded albumin nanoparticles (PS@chol-BSA NPs). In this study, the photodynamic therapeutic effect of PS@chol-BSA NPs was further enhanced by confinement of light using a fiber optic cannula in orthotopic GBM-xenografted mice. In vitro cellular uptake and phototoxicity of PS@chol-BSA NPs were evaluated in brain tumor (U87MG) and endothelial (bEnd.3) cells. In vivo biodistribution was determined by an in vivo imaging system (IVIS) and the photodynamic efficacy was evaluated with confined laser irradiation. PS@chol-BSA NPs showed higher cellular uptake and phototoxicity in U87MG cells than in bEnd.3 cells. PS@chol-BSA NPs showed a brain tumor accumulation of 0.2%ID within 2 h and remain in the brain tumor for 22 h. When compared to the control group, there was remarkable suppression in tumor growth by laser irradiation with and without the fiber optic cannula at a dose of 1 mg kg-1, in which significant tumor suppression up to 40% was observed with confined laser irradiation. Together, dual-selective photodynamic therapy with a mitochondria-targeted photosensitizer and fiber optic cannula provides a promising therapeutic strategy for malignant brain tumors.

Organic small molecule for detection and photodegradation of mitochondrial DNA mutations.

A detection and degradation platform was developed to optically quantify the 6-enolate, 8-keto-dG, an important tautomer of mitochondrial mutated DNA 8-oxo-dG. We first found that 6-enolate, 8-keto-dG offers particular fluorescence emission under the conditions between pH ∼ 7 and ∼11. Thus, a mitochondria-targeting photosensitizer NV-12P was prepared to offer simultaneously photoinduced electron transfer and fluorescence resonance energy transfer (FRET) with 6-enolate, 8-keto-dG. Furthermore, NV-12P can also generate a reactive oxygen species to degrade 6-enolate, 8-keto-dG under irradiation conditions. This is the first publication about optical characterization, concentration detection and photodegradation of 6-enolate, 8-keto-dG, either in biological or in vitro applications.

Nanoparticles as mitochondria-targeted photosensitizer in photodynamic therapy of cancer

Nanoparticles as mitochondria-targeted photosensitizer in photodynamic therapy of cancer