Mitochondria-targeted Photodynamic Therapy Research Articles

Golgi apparatus-targeted BODIPY-based photosensitizer synergized with glutaminase inhibition for enhanced photodynamic therapy

Photodynamic therapy (PDT) is a precise and less toxic side effect treatment strategy. However, the inherently short lifespan and constrained diffusion range of reactive oxygen species within the cellular milieu can attenuate the therapeutic efficacy of cytoplasmic photosensitizers. Organelle-targeted PDT is thus proposed. Although the essence of PDT is the photosensitization reaction accompanied by biological effects involving aerobic molecules, mitochondria-targeted PDT may lead to the emergence of drug resistance in tumor cells triggered by mitochondrial damage. Thus, developing more types of organelle-targeted PDT strategies is the key to avoiding this problem. Herein, a fluoroboron dipyrrole-based photosensitizer, OFBDP, with Golgi apparatus-targeted and PDT ability is designed and synthesized. Furthermore, considering the effect of high concentrations of reduced glutathione in tumor cells, the addition of glutaminase inhibitor, compound 968 (C968), synergistically enhanced the PDT efficacy of OFBDP by indirectly inhibiting intracellular glutathione synthesis through its effect on glutamine metabolism. The OFBDP/C968 combination has demonstrated an enhanced tumor ablation capability. This work generally provides a strategy for the potential of organelle-targeted PDT to improve treatment outcomes, but also contribute to the burgeoning field of subcellular photosensitizer research.

Benzothiazolium-based NIR AIE photosensitizers with type I and II ROS generation for efficient mitochondria-targeted photodynamic therapy.

In this work, a near-infrared emissive photosensitizer of 3,3-dimethyl-N,N-diphenyl-2-(thiophen-2-yl)-3H-indol-6-amine functionlized benzothiazolium (DPITT) was developed. DPITT exhibited aggregation-induced emission effect and potent type I and II reactive oxygen species generation capacities after white light irradiation. Taking advantage of the cationic feature, DPITT penetrated the cell membrane and selectively accumulated in the mitochondria in living cells. Upon white light irradiation, the photosensitized DPITT was able to induce mitochondrial dysfunction, leading to cell death. Photosensitized DPITT was further applied to disrupt the multicellular tumour spheroids, demonstrating its potential application in inhibiting hypoxic solid tumours.

Mitochondria-targeted photodynamic therapy triggers GSDME-mediated pyroptosis and sensitizes anti-PD-1 therapy in colorectal cancer

BackgroundThe effectiveness of immune checkpoint inhibitors in colorectal cancer (CRC) is limited due to the low tumor neoantigen load and low immune infiltration in most microsatellite-stable (MSS) tumors. This study...

Photodynamic Therapy Induced Mitochondrial Targeting Strategies for Cancer Treatment: Emerging Trends and Insights.

The perpetuity of cancer prevalence at a global level calls for development of novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional cancer treatments have a multitude of limitations such as nonselectivity, invasive nature, and severe adverse effects. Chemotherapy is also losing its efficacy because of the development of multidrug resistance in the majority of cancers. To address these issues, selective targeting-based approaches are being explored for an effective cancer treatment. Mitochondria, being the moderator of a majority of crucial cellular pathways like metabolism, apoptosis, and reactive oxygen species (ROS) homeostasis, are an effective targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen as a potential approach in this endeavor. By designing photosensitizers (PSs) that preferentially accumulate in the mitochondria, PDT offers a localized technique to induce cytotoxicity in cancer cells. In this review, we intend to explore the crucial principles and challenges associated with mitochondria-targeted PDT, including variability in mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, and combination therapies. The hurdles faced by this emerging strategy with respect to safety, optimization, clinical translation, and scalability are also discussed. Nonetheless, mitochondria-targeted PDT exhibits a significant capacity in cancer treatment, especially in combination with other therapeutic modalities. With perpetual research and technological advancements, this treatment strategy is a great addition to the arsenal of cancer treatment options, providing better tumor targetability while reducing the damage to surrounding healthy tissues. This review emphasizes the current status of mitochondria-targeted PDT, limitations, and future prospects in its pursuit of safe and efficacious cancer therapy.

Triphenylphosphonium-functionalized dimeric BODIPY-based nanoparticles for mitochondria-targeting photodynamic therapy.

The dimerization of boron dipyrromethene (BODIPY) moieties is an appealing molecular design approach for developing heavy-atom-free triplet photosensitizers (PSs). However, BODIPY dimer-based PSs generally lack target specificity, which limits their clinical use for photodynamic therapy. This study reports the synthesis of two mitochondria-targeting triphenylphosphonium (TPP)-functionalized meso-β directly linked BODIPY dimers (BTPP and BeTPP). Both BODIPY dimers exhibited solvent-polarity-dependent singlet oxygen (1O2) quantum yields, with maximum values of 0.84 and 0.55 for BTPP and BeTPP, respectively, in tetrahydrofuran. The compact orthogonal geometry of the BODIPY dimers facilitated the generation of triplet excited states via photoinduced charge separation (CS) and subsequent spin-orbit charge-transfer intersystem crossing (SOCT-ISC) processes and their rates were dependent on the energetic configuration between the frontier molecular orbitals of the two BODIPY subunits. The as-synthesized compounds were amphiphilic and hence formed stable nanoparticles (∼36 nm in diameter) in aqueous solutions, with a zeta potential of ∼33 mV beneficial for mitochondrial targeting. In vitro experiments with MCF-7 and HeLa cancer cells indicated the effective localization of BTPP and BeTPP within cancer-cell mitochondria. Under light irradiation, BTPP and BeTPP exhibited robust photo-induced therapeutic effects in both cell lines, with half-maximal inhibitory concentration (IC50) values of ∼30 and ∼55 nM, respectively.

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy.

Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a two-dimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.

π-extended porphyrin-based near-infrared photosensitizers for mitochondria-targeted photodynamic therapy

Near-infrared (NIR) photosensitizers have great potential to develop various fields of photochemistry, such as photodynamic therapy (PDT) and photocatalysts. Organelle-targeted PDT using NIR light attracts considerable attention to high-efficiency phototherapy. Although drug delivery system (DDS) carriers are often combined with NIR photosensitizers for effective PDT, the systematic correlations between the cargo and DDS carriers are still unclear. In this study, we develop NIR-photosensitizers from a π-extended porphyrin-type sensitizer (rTPA) that allows us to modify the structure and properties with a one-touch operation for the systematic study. Single-step amidations give five rTPA derivatives readily, facilitating comprehensive information about the properties according to their molecular structure and electric charge of the photosensitizer and DDS carriers prepared using a microfluidic device. One of the combinations, rTPA-NH2@MP, demonstrates the highest ability among the derivatives to kill pancreatic cancer cells, which are known to be highly lethal. The present study provides a guideline for inventing effective DDS-based NIR-PDT compounds for future photodrugs.

A Platinum(II) Boron-dipyrromethene Complex for Cellular Imaging and Mitochondria-targeted Photodynamic Therapy in Red Light.

Cisplatin-derived platinum(II) complexes [Pt(NH3 )2 (pacac)](NO3 ) (1, DPP-Pt) and [Pt(NH3 )2 (Acac-RB)](NO3 ) (2, Acacplatin-RB), where Hpacac is 1,3-diphenyl-1,3-propanedione and HAcac-RB is a red-light active distyryl-BODIPY-appended acetylacetone ligand, are prepared, characterized and their photodynamic therapy (PDT) activity studied (RB abbreviated for red-light BODIPY). Complex 2 displayed an intense absorption band at λ=652 nm (ϵ=7.3×104 M-1 cm-1 ) and 601 nm (ϵ=3.1×104 M-1 cm-1 ) in 1 : 1 DMSO-DPBS (Dulbecco's Phosphate Buffered Saline). Its emission profile includes a broad maximum at ~673 nm (λex =630 nm). The fluorescence quantum yield (ΦF ) of HAcac-RB and 2 are 0.19 and 0.07, respectively. Dichlorodihydrofluorescein diacetate and 1,3-diphenylisobenzofuran assay of complex 2 indicated photogeneration of singlet oxygen (ΦΔ : 0.36) as reactive oxygen species (ROS). Light irradiation caused only minor extent of ligand release forming chemo-active cisplatin analogue. The complex showed ~70-100 fold enhancement in cytotoxicity on light exposure in A549 lung cancer cells and MDA-MB-231 multidrug resistant breast cancer cells, giving half maximal inhibitory concentration (IC50 ) of 0.9-1.8 μM. Confocal imaging showed its mitochondrial localization and complex 2 exhibited anti-metastasis properties. Immunostaining of β-tubulin and Annexin V-FITC/propidium iodide staining displayed complex 2 induced photo-selective microtubule rupture and cellular apoptosis, respectively.

Photoactivated DNA Nanodrugs Damage Mitochondria to Improve Gene Therapy for Reversing Chemoresistance.

Multidrug resistance (MDR) is a major cause of chemotherapy failure in oncology, and gene therapy is an excellent measure to reverse MDR. However, conventional gene therapy only modulates the expression of MDR-associated proteins but hardly affects their existing function, thus limiting the efficiency of tumor treatment. Herein, we designed a photoactivated DNA nanodrug (MCD@TMPyP4@DOX) to improve tumor chemosensitivity through the downregulation of MDR-related genes and mitochondria-targeted photodynamic therapy (PDT). The self-assembled DNA nanodrug encodes the mucin 1 (MUC1) aptamer and the cytochrome C (CytC) aptamer to facilitate its selective targeting to the mitochondria in tumor cells; the encoded P-gp DNAzyme can specifically cleave the substrate and silence MDR1 mRNA with the help of Mg2+ cofactors. Under near-infrared (NIR) light irradiation, PDT generates reactive oxygen species (ROS) that precisely damage the mitochondria of tumor cells and break single-stranded DNA (ssDNA) to activate MCD@TMPyP4@DOX self-disassembly for release of DOX and DNAzyme. We have demonstrated that this multifunctional DNA nanodrug has high drug delivery capacity and biosafety. It enables downregulation of P-gp expression while reducing the ATP on which P-gp pumps out drugs, improving the latency of gene therapy and synergistically reducing DOX efflux to sensitize tumor chemotherapy. We envision that this gene-modulating DNA nanodrug based on damaging mitochondria is expected to provide an important perspective for sensitizing tumor chemotherapy.

Efficient NIR-II Type-I AIE Photosensitizer for Mitochondria-Targeted Photodynamic Therapy through Synergistic Apoptosis-Ferroptosis.

Hypoxia, the hallmark of malignant tumors, has been recognized as a major obstacle for photodynamic therapy (PDT). Precisely targeting cancer cells in intricate biological scenarios by a hypoxia-resistant photosensitizer (PS) is the cornerstone to conquer the inevitable tumor recurrence and metastasis. Herein, we describe an organic NIR-II PS (TPEQM-DMA) possessing potent type-I phototherapeutic efficacy to overcome the intrinsic pitfalls of PDT in combating hypoxic tumors. TPEQM-DMA exhibited prominent NIR-II emission (>1000 nm) with an aggregation-induced emission feature and efficiently produced superoxide anion and hydroxyl radical in the aggregate state under white light irradiation exclusively through a low-O2-dependent type-I photochemical process. The suitable cationic nature assisted TPEQM-DMA to accumulate in cancerous mitochondria. Meanwhile, the PDT of TPEQM-DMA impaired the cellular redox homeostasis, led to the mitochondrial dysfunction, and raised the level of lethal peroxidized lipids, which induced cellular apoptosis and ferroptosis. This synergistic cell death modality enabled TPEQM-DMA to suppress the growth of cancer cells, multicellular tumor spheroids, and tumors. To improve the pharmacological properties of TPEQM-DMA, TPEQM-DMA nanoparticles were prepared by encapsulation of polymer. In vivo experiments proved the appealing NIR-II fluorescence imaging-guided PDT effect of TPEQM-DMA nanoparticles for tumors.

Near-infrared AIE-active phosphorescent iridium(III) complex for mitochondria-targeted photodynamic therapy.

Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (∼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.

An X-ray activatable gold nanorod encapsulated liposome delivery system for mitochondria-targeted photodynamic therapy (PDT).

In this work, we developed a mitochondria-targeted nanomaterial for neoadjuvant X-ray-triggered photodynamic therapy of rectal cancer. Herein, we designed a biodegradable liposome incorporating a photosensitizer, verteporfin, to generate X-ray-induced reactive oxygen species, gold nanorods as radiation enhancers, and triphenylphosphonium as the mitochondrial targeting moiety. The average size of the nanocarrier was about 150 nm. Due to the synergetic effect between X-ray and a combination of verteporfin and gold nanorods, as well as precise site-targeted TPP-modified liposomal nanocarriers, our nanoconjugates generated sufficient cytotoxic singlet oxygen within the mitochondria under X-ray irradiation, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells.

Photophysical properties and aggregation behavior of diethylene glycol substituted pyropheophorbide-a in cationic surfactant solutions

The aggregation behavior of a novel amphiphilic photosensitizer - pyropheophorbide-[Formula: see text] 17-diethylene glycol ester 1 was studied in aqueous and aqueous-organic mixtures by means of steady-state absorption and fluorescence emission spectroscopy. The formation of [Formula: see text]-aggregates with a bathochromic shift of the absorption bands, weak fluorescence and resonance enhancement of the light scattering was observed in the mixed water-organic solvents. Solubilization studies in micellar cationic surfactant solutions of alkyl trimethylammonium bromides (C[Formula: see text]TAB) and alkyl triphenylphosphonium bromides (C[Formula: see text]TPPB) resulted in the most effective stabilization of the fluorescent monomolecular form of 1 in C[Formula: see text]TPPB micelles. It was shown that [Formula: see text]-aggregate formation in submicellar surfactant solutions is the initial stage of the solubilization process, which significantly increases in phosphate buffer medium at pH 7.4. Fluorescence lifetime ([Formula: see text] of 1 in DMSO was found to be 7.4 ns, fluorescence quantum yield - 34% and singlet oxygen quantum yield - 62%. The results obtained indicate the need for further studies of compound 1 solubilized in C[Formula: see text]TPPB micelles as the most promising prototype of the drug formulation for mitochondria-targeted photodynamic therapy of cancer.

Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy

BackgroundMitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge.MethodsHerein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core.ResultsInside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo.ConclusionsThis oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.

Mitochondria-Driven Dye Rearrangement That Enables Spatiotemporally Controlled Photomedicine.

Reversibly controlling the dye arrangements in living systems has great potential to realize spatiotemporally controlled photomedicine. However, tuning or even maintaining a certain arrangement of dyes in a complex living environments is extremely challenging due to the interference of the various biological species. Herein, a conceptual supramolecular strategy to engineer a switchable photosensitizer (PS) via mitochondria-mediated dynamic interconversion between monomer and J-aggregation, enabling specific activation of the mitochondria-targeting photodynamic therapy (PDT) and hibernation after mitochondria damage is presented. The presented mitochondria-mediated "activate-then-hibernate" PS design enables a fascinating spatiotemporally controlled PDT in which spatially controlled mitochondrial-targeting enhances therapeutic efficacy and temporally controlled activation-then-hibernation averts off-target damage during PDT and tissue damage after clinical treatment, thus offering significant potential for biological research and clinical needs.

Mitochondria-targeted nanoplatforms building for in situ ROS generating photodynamic tumor therapy through reinforcing mitochondria apoptotic pathway

Mitochondria-targeted photodynamic therapy (PDT) represents an attractive therapeutic strategy for antitumor therapy. There is growing evidence indicating that in situ generation of reactive oxygen species (ROS) in mitochondria plays a critical role in significant mitochondrial dysfunction and cell apoptosis. Nevertheless, survivin, a member of the inhibitor of apoptosis protein (IAP) family, is overexpressed by PDT stimulation, which inhibit cysteine aspartic acid specific protease-9 (caspase-9) activation and inhibits apoptosis. The corresponding overexpression of Livin protein in tumor cells can inhibit cysteine aspartic acid specific protease-3 (caspase-3) activity, leading to apoptosis inhibition and promoting tumorigenesis and tumor progression. Thus, a precise combination of mitochondria-targeted photodynamic photosensitizers and IAP inhibitor is expected to significantly augment the PDT efficacy. For proof-of-concept, a therapeutic nanoplatform MSNs/GM/I3C-BSA/MnO2-IR775 (MGIBR) was ingeniously constructed for synergistic cancer therapy. MGIBR can effectively target mitochondria due to the presence of IR775. Under NIR irradiation, MGIBR can generate in situ 1O2 in mitochondria. Importantly, geldanamycin (GM) and indole-3-carbinol (I3C) can inhibit IAP, synergistic enhance PDT and activate mitochondrial apoptosis pathways, leading to effectively cell death. Such a strategy of MGIBR enabled mitochondrial dysfunction based on in situ generation of ROS in mitochondria and IAP inhibitor synergistically, provides a promising paradigm for highly effective cancer therapeutics.

Highly efficient singlet oxygen generation of AIE luminogens enable mitochondria-targeted photodynamic therapy

The development of aggregation-induced emission luminogens (AIEgens) with high brightness and efficient photodynamic therapy (PDT) is of great value for the precise diagnosis and treatment of cancers. In this contribution, two novel AIEgens, TBBCyP and TBTCyP with D-A-π-A structure, were designed and prepared based on molecular rational design of electron-donating receptors. Experimental and theoretical results indicated that both TBBCyP and TBTCyP own bright AIE feature, satisfy photos ability, and generate efficient singlet oxygen (1O2). Notably, TBBCyP exhibited brighter emission and higher 1O2 yield in compared with TBTCyP, which could be ascribed to its weaker twisted intramolecular charge transfer (TICT) effect and narrower singlet-triplet energy gap (ΔEST). Moreover, it was proved that TBBCyP and TBTCyP showed a great mitochondrial specificity and desired intracellular ROS productivity for realizing the effective mitochondria-targeted PDT of cancer cells.

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

BackgroundRadiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval.MethodsHerein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells’ mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers.ResultsWhen tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts.ConclusionsOur studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation.Graphical

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.

A photosensitive sustainable lignin nanoplatform for multimodal image-guided mitochondria-targeted photodynamic and photothermal therapy

Photoactivated nanocarriers exhibit significant potential for anticancer therapy, but complex design strategies, unsustainable substrates, and short wavelengths limit their practical application. Here, we designed a new lignin-derived photoactivated nanomaterial that exploits the sensitivity of the β-O-4 bond of lignin to singlet oxygen. This sustainable product was loaded with mitochondria-targeting chlorin e6 and black phosphorus quantum dots (BPQDs) to produce BPQDs@N-LgC NPs, which were used for mitochondria-targeted fluorescence/photoacoustic-guided photothermal and photodynamic therapy. When irradiated at 808 nm, the BPQDs in BPQDs@N-LgC NPs exhibited good photothermal conversion, which allowed photoacoustic imaging and inhibited tumor growth. When irradiated at 660 nm, the BPQDs@N-LgC NPs generated fluorescence and reactive oxygen species, which allowed photoluminescence imaging and further inhibited tumor growth. Cleavage of the β-O-4 bond of lignin by photo-triggered reactive oxygen species degraded the NPs and released the BPQDs, facilitating rapid excretion of the therapeutic nanomaterials. Our rationally designed BPQDs@N-LgC NPs exhibited good therapeutic efficacy, both in vitro and invivo.