Conventional Photodynamic Therapy Research Articles

Comparison of the Differences between Two-Photon Excitation, Upconversion, and Conventional Photodynamic Therapy on Cancers in In Vitro and In Vivo Studies

Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of ‘caged’ imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers. Methods: Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review. Results: TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers. Conclusions: Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.

Heavy atom-modified hemicyanine dyes as photosensitizer scaffolds combined with nitric oxide trigger the butterfly effect in tumor therapy

Hypoxia is a common feature of solid tumors and is considered to be the fatal flaw of conventional photodynamic therapy (PDT), which severely reduces the overall therapeutic efficacy. Here, we developed a series of halogenated photosensitizers to address this issue. The results showed that the introduction of heavy atoms enhanced the spin-coupling effect of the photosensitizers and effectively improved the type I PDT (non-oxygen-dependent) efficiency. The preferred iodine-substituted photosensitizer NRh–I was used as the basic architecture, and further nitrosyl modification was performed to obtain the NO small-molecule prodrug, which was finally encapsulated with DSPE-mPEG5k to obtain a biocompatible NO nanophotocontrolled prodrug. By using the enhanced permeability and retention effect (EPR), the prodrug system can precisely target the lesion site, release a high concentration of NO by photocontrol, kill the tumor cells, and at the same time, cascade with ROS released with the same “time-space” precision to generate higher cytotoxicity, ONOO−, which generates a stronger targeted synergistic therapeutic effect. This “butterfly effect” strategy maximizes the effect of PDT and broadens the idea of translational medicine.

Enriched photosensitizer for deep-seated-tumor photodynamic therapy

Photodynamic therapy (PDT) is an innovative approach that utilizes photochemical reactions for non-invasive disease treatment. Conventional PDT is limited by the low penetration depth of visible light required for activation. Herein, we employed upconversion nanoparticles (UCNPs) to extend the activation wavelength of photosensitizers into the infrared range, enabling a treatment depth of over 10 mm. Furthermore, we also used the abundant amino groups of branched polyethyleneimine (PEI) with spatial structure to enhance the loading capacity of protoporphyrin (PPIX), and we ultimately improved skin tumor clearance rates. Moreover, we achieved tumor-specific treatment by utilizing folic acid (FA) targeting and active enrichment of PPIX. According to cellular experimental results, we demonstrated the remarkable reactive oxygen species generation capability of the material and ultra-low dark toxicity. Additionally, we investigated the apoptosis mechanism and demonstrated that the synthesized nanoparticle stimulates the up-regulation of apoptosis-associated proteins Bax/Bcl-2 and Cyto c. During in vivo experiments involving intravenous injection in mouse tails, we investigated the anticancer efficacy of the nanoparticle, confirming its excellent PDT effects. This research provides a promising avenue for future non-invasive treatment of deep-seated tumors, offering a method for the treatment and management of specific cancers.

Photodynamic Therapy for the Treatment of Bowen's Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome.

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

Modified Painless Photodynamic Therapy for Actinic Keratosis in China

SignificanceAminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for actinic keratosis (AK). However, the pain during illumination usually caused patient to discontinue PDT treatment and resulted lower efficacy. Previous study showed modified painless PDT (M-PDT) with short ALA incubation time and longer irradiation time can reduce pain and preserve the efficacy. If M-PDT worked in AK still need to investigate. ApproachA splie-face controlled clinical study was conducted. Eleven patients with facial AK received C-PDT (conventional PDT) on the left and M-PDT in the contralateral area. The left area was illuminated by a red LED light (a total light dose of 140 J/cm2) after applying the ALA cream for 3 hours; the other had illumination for a total light dose of 288 J/cm2 after applying the ALA cream for 0.5 hours. The primary endpoint was the lesion clearance rate at 1 month. Secondary endpoints included pain scores, the incidence of adverse events, and cosmetic outcomes. ResultsAt one month following 3 treatments, the lesion clearance rate of M-PDT was non-inferior to that of C-PDT (93.1% vs. 86.4%, respectively. The lesion clearance rate of M-PDT to reach 100% clearance earlier than C-PDT for grade I lesions and higher clearance rates for grade III lesions. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (P < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment (GS2A2) score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. ConclusionsM-PDT is non-inferior to C-PDT in terms of efficacy for treating AK, resulting in much lower pain scores.

Piezo-photodynamic therapy of Au@PEG-ZnO nanostructures enabled with a battery-free wireless cancer therapeutic dot

Cancer remains a global health concern, necessitating advanced therapeutic strategies to address its fatal challenges. Conventional treatments, such as radiotherapy and chemotherapy, often lack tumor specificity and may induce systemic toxicity. Photodynamic therapy (PDT) and sonodynamic therapy (SDT) have emerged as promising alternatives, demonstrating high specificity and minimal side effects. In this study, we propose a novel piezo-photodynamic therapy (PPDT) enabled with battery-free wireless cancer therapeutic dot, in which the nanocomposites of gold nanoparticles (Au NPs), zinc oxide nanorods (ZnO NRs) and hydrophilic polyethylene glycol (PEG) can enhance reactive oxygen species (ROS) generation and effectively inhibit tumor growth. The therapeutic dot is implanted directly inside the tissue around the tumor and wirelessly controlled by ultrasound (US), allowing dual activation of electron-hole pairs from the nanocomposites via US and ultraviolet light (UV). The internally generated piezoelectric field minimizes electron-hole recombination, maximizing ROS induction within tumor cells. This PPDT approach surpasses the efficacy of conventional PDT and SDT, showcasing a synergistic therapeutic effect. The study further elucidates the detailed mechanism of Au@PEG-ZnO NRs catalysts, providing insights into their piezoelectric-photocatalytic action. The battery-free wireless control and minimally invasive implantation of the therapeutic dot with inorganic piezo-photocatalyst open new perspectives in cancer therapy.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis

BackgroundConventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies. ObjectiveTo compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. MethodsWe conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a “blinded” investigator. ResultsLesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas. ConclusionThe occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.

Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy.

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.

A Less-is-More Strategy for Mitochondria-Targeted Photodynamic Therapy of Rheumatoid Arthritis.

Conventional photodynamic therapy (PDT) of rheumatoid arthritis (RA) faces a dilemma: low-power is insufficient to kill pro-inflammatory cells while high-power exacerbates inflammation. Herein, mitochondrial targeting is introduced in PDT of RA to implement a "less-is-more" strategy, where higher apoptosis in pro-inflammatory cells are achieved with lower laser power. In arthritic rats, chlorine 6-loaded and mitochondria-targeting liposomes (Ce6@M-Lip) passively accumulated in inflamed joints, entered pro-inflammatory macrophages, and actively localized to mitochondria, leading to enhanced mitochondrial dysfunction under laser irradiation. By effectively disrupting mitochondria, pro-inflammatory macrophages are more susceptible to PDT, resulting in increased apoptosis initiation. Additionally, it identifies that high-power irradiation caused cell rupture and release of endogenous danger signals that recruited and activated additional macrophages. In contrast, under low-power irradiation, mitochondria-targeting Ce6@M-Lip not only prevented inflammation but also reduced pro-inflammatory macrophage infiltration and pro-inflammatory cytokine secretion. Overall, targeting mitochondria reconciled therapeutic efficacy and inflammation, thus enabling efficacious yet inflammation-sparing PDT for RA. This highlights the promise of mitochondrial targeting to resolve the dilemma between anti-inflammatory efficacy and inflammatory exacerbation in PDT by implementing a "less-is-more" strategy.

Zinc phthalocyanine loaded- antibody functionalized nanoparticles enhance photodynamic therapy in monolayer (2-D) and multicellular tumour spheroid (3-D) cell cultures.

In conventional photodynamic therapy (PDT), effective delivery of photosensitizers (PS) to cancer cells can be challenging, prompting the exploration of active targeting as a promising strategy to enhance PS delivery. Typically, two-dimensional (2-D) monolayer cell culture models are used for investigating targeted photodynamic therapy. However, despite their ease of use, these cell culture models come with certain limitations due to their structural simplicity when compared to three-dimensional (3-D) cell culture models such as multicellular tumour spheroids (MCTSs). In this study, we prepared gold nanoparticles (AuNPs) that were functionalized with antibodies and loaded with tetra sulphonated zinc phthalocyanine (ZnPcS4). Characterization techniques including transmission electron microscopy (TEM) was used to determine the size and morphology of the prepared nanoconjugates. We also conducted a comparative investigation to assess the photodynamic effects of ZnPcS4 alone and/or conjugated onto the bioactively functionalized nanodelivery system in colorectal Caco-2 cells cultured in both in vitro 2-D monolayers and 3-D MCTSs. TEM micrographs revealed small, well distributed, and spherical shaped nanoparticles. Our results demonstrated that biofunctionalized nanoparticle mediated PDT significantly inhibited cell proliferation and induced apoptosis in Caco-2 cancer monolayers and, to a lesser extent, in Caco-2 MCTSs. Live/dead assays further elucidated the impact of actively targeted nanoparticle-photosensitizer nanoconstruct, revealing enhanced cytotoxicity in 2-D cultures, with a notable increase in dead cells post-PDT. In 3-D spheroids, however, while the presence of targeted nanoparticle-photosensitizer system facilitated improved therapeutic outcomes, the live/dead results showed a higher number of viable cells after PDT treatment compared to their 2-D monolayer counterparts suggesting that MCTSs showed more resistance to PS drug as compared to 2-D monolayers. These findings suggest a high therapeutic potential of the multifunctional nanoparticle as a targeted photosensitizer delivery system in PDT of colorectal cancer. Furthermore, the choice of cell culture model influenced the response of cancer cells to PDT treatment, highlighting the feasibility of using MCTSs for targeted PS delivery to colorectal cancer cells.

Engineering tumor-oxygenated nanomaterials: advancing photodynamic therapy for cancer treatment.

Photodynamic therapy (PDT), a promising treatment modality, employs photosensitizers to generate cytotoxic reactive oxygen species (ROS) within localized tumor regions. This technique involves administering a photosensitizer followed by light activation in the presence of oxygen (O2), resulting in cytotoxic ROS production. PDT's spatiotemporal selectivity, minimally invasive nature, and compatibility with other treatment modalities make it a compelling therapeutic approach. However, hypoxic tumor microenvironment (TME) poses a significant challenge to conventional PDT. To overcome this hurdle, various strategies have been devised, including in-situ O2 generation, targeted O2 delivery, tumor vasculature normalization, modulation of mitochondrial respiration, and photocatalytic O2 generation. This review aims to provide a comprehensive overview of recent developments in designing tumor-oxygenated nanomaterials to enhance PDT efficacy. Furthermore, we delineate ongoing challenges and propose strategies to improve PDT's clinical impact in cancer treatment.

Synthesis of lanthanide-based scintillator@MOF nanocomposites for X-ray-induced photodynamic therapy

Nanocomposites were proposed and fabricated to simultaneously generate singlet oxygen (1O2) through energy transfer from SNPs to Hf-TCPP and hydroxyl radicals (˙OH) by the introduction of high-Z elements under low-dose X-ray irradiation.

Recent advances in aggregation-induced emission-active type I photosensitizers with near-infrared fluorescence: From materials design to therapeutic platform fabrication.

Near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self-aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π-π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence-guided type I PSs with aggregation-induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE-active PDT based on type I PSs. In this review, cutting-edge advances focusing on AIE-active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE-active type I PSs are proposed.

Lipid Droplet Targeting Type I Photosensitizer for Ferroptosis via Lipid Peroxidation Accumulation.

As an iron-dependent lipid peroxidation (LPO) mediated cell death pathway, ferroptosis offers promises for anti-tumor treatment. Photodynamic therapy (PDT) is an ideal way to generate reactive oxygen species (ROS) for LPO. However, the conventional PDT normally functions on subcellular organelles, such as endoplasmic reticulum, mitochondria, and lysosome, causing rapid cell death before triggering ferroptosis. Herein, the first lipid droplet (Ld)-targeting type I photosensitizer (PS) with enhanced superoxide anion (O2 -· ) production, termed MNBS, is reported. The newly designed PS selectively localizes at Ld in cells, and causes cellular LPO accumulation by generating sufficient O2 -· upon irradiation, and subsequently induces ferroptosis mediated chronical PDT, achieving high-efficient anti-tumor PDT in hypoxia and normoxia. Theoretical calculations and comprehensive characterizations indicate that the Ld targeting property and enhanced O2 -· generation of MNBS originate from the elevated H-aggregation tendency owing to dispersed molecular electrostatic distribution. Further in vivo studies using MNBS-encapsulated liposomes demonstrate the excellent anti-cancer efficacy as well as anti-metastatic activity. This study offers a paradigm of H-aggregation reinforced type I PS to achieve ferroptosis-mediated PDT.

Design of a novel nanoparticle to use X-ray fluorescence of TiO2 to induce photodynamic effects in the presence of PpIX

BackgroundRadiotherapy and photodynamic therapy are the methods of cancer treatment. Although one limitation of photodynamic therapy (PDT) is the limited penetration depth of light through tissue, using X-rays does not have this restriction. Self-lighting nanoparticles can convert X-rays into UV/visible. This study focuses on a newly designed nanostructure containing mesoporous silica nanoparticles (MSN), titanium dioxide nanoparticles (TiO2, anatase grade), and protoporphyrin IX (PpIX) as a photosensitizer to overcome the limitations of photodynamic therapy. MethodsAfter the synthesis and characterization of Ti-MSN/PpIX@PVP nanostructure, two ROSes (OH* and 1O2) were measured when the nanostructures were irradiated with 100 kV and 6 MV photons. The toxicity of Ti-MSN/PpIX@PVP nanostructure in presence and absence of radiation was investigated on DFW and HT-29 cell lines. The in-vitro experiments were analyzed using the MTT assay and colony count assay. Finally, the effect of light exposure in the presence of Ti-MSN/PpIX@PVP nanostructure on the two cell lines was studied. The in-vitro studies were evaluated using the Synergism Index (Syn) and Dose Enhancement Factor (DEF). ResultsBased on the FESEM (field emission scanning electron Microscopy) images and DLS (dynamic light scattering) measurements, the size of Ti-MSN/PpIX nanostructure was determined as (35.2 nm) and (168.4 nm), respectively. Based on the spectrofluorimetry results, 100 kV photons produced more ROSes than 6 MV photons. The results of MTT assay and colony formation for X-PDT show Syn >1, except for 100 kV photons for HT-29 cell line. The nanostructure also reduced colony formation induced by X-PDT more effectively when irradiated by 100 kV photons on DFW cells. The results obtained from conventional PDT showed that the ED 50 of the HT-29 cell line was 6 times higher than that of the DFW cell line. ConclusionDesigning and synthesizing Ti-MSN/PpIX@PVP nanostructures offer a promising strategy for reducing the current challenges in PDT and for developing and advancing X-PDT as an innovative cancer treatment technique.

Modified painless photodynamic therapy for facial multiple actinic keratosis in China: A prospective split-face control study.

Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown. To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK. A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes. At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores.

A sequential dual-locked strategy with pH-responsive activation of photosensitizers and precise Cerenkov radiation delivery for cancer theranostics

Cerenkov radiation (CR)-induced therapy (CRIT) has emerged as a promising modality to overcome the limitation of light penetration in conventional photodynamic therapy (PDT). Nevertheless, achieving a balance between efficacy and safety of CRIT remains a significant challenge. Here, we propose a dual-locked strategy that sequentially delivers a pH-activatable photosensitizer, bovine serum albumin (BSA)-packed chlorin e6 (Ce6) and MnO2 nanodots (BCM), and 68Ga-labeled CD47-targeting C2 nanobody (68Ga-C2) for safe and effective CRIT in tumors. BCM serves as both a tumor microenvironment (TME) modulator and a pH-activatable photosensitizer, which exhibits minimal phototoxicity in normal tissues due to its quenched fluorescence and attenuated inter-system crossing (ISC) induced by MnO2 nanodots. Upon exposure to the acidic TME, BCM “unlocks” its bifunctionality, triggering a self-cascade catalysis reaction to supply O2 and cytotoxic HO·, while simultaneously depleting GSH. Cerenkov radiation from 68Ga-C2, subsequently delivered, illuminates the activated Ce6 molecules in BCM, inducing a burst generation of singlet oxygen, which is further enhanced by the pre-modulated TME. The acidic TME and tumor-targeting 68Ga-C2 provide two “keys” to ensure a selective reactive oxygen species (ROS) burst in the tumor sites while minimizing ROS generation in normal tissues. This pH-activatable CRIT induces DNA damage and mitochondrial dysfunction of tumor cells, effectively suppressing tumor growth with minimal side effects on CD47-expressing LS174T tumor models. This study highlights the potential of using pH-activatable photosensitizers in cancer therapy and provides a reference for future research in CR-induced tumor theranostics.

Fully implantable and battery-free wireless optoelectronic system for modulable cancer therapy and real-time monitoring

Photodynamic therapy (PDT) is attracting attention as a next-generation cancer treatment that can selectively destroy malignant tissues, exhibit fewer side effects, and lack pain during treatments. Implantable PDT systems have recently been developed to resolve the issues of bulky and expensive conventional PDT systems and to implement continuous and repetitive treatment. Existing implantable PDT systems, however, are not able to perform multiple functions simultaneously, such as modulating light intensity, measuring, and transmitting tumor-related data, resulting in the complexity of cancer treatment. Here, we introduce a flexible and fully implantable wireless optoelectronic system capable of continuous and effective cancer treatment by fusing PDT and hyperthermia and enabling tumor size monitoring in real-time. This system exploits micro inorganic light-emitting diodes (μ-LED) that emit light with a wavelength of 624 nm, designed not to affect surrounding normal tissues by utilizing a fully programmable light intensity of μ-LED and precisely monitoring the tumor size by Si phototransistor during a long-term implantation (2–3 weeks). The superiority of simultaneous cancer treatment and tumor size monitoring capabilities of our system operated by wireless power and data transmissions with a cell phone was confirmed through in vitro experiments, ray-tracing simulation results, and a tumor xenograft mouse model in vivo. This all-in-one single system for cancer treatment offers opportunities to not only enable effective treatment of tumors located deep in the tissue but also enable precise and continuous monitoring of tumor size in real-time.

Pure Organic AIE Nanoscintillator for X-ray Mediated Type I and Type IIPhotodynamic Therapy.

X-ray induced photodynamic therapy (X-PDT) circumvents the poor penetration depth of conventional PDT with minimal radio-resistance generation. However, conventional X-PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation-induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X-ray irradiation is reported for hypoxia-tolerant X-PDT. Heteroatoms are introduced to enhance X-ray harvesting and ROS generation ability, and AIE-active TBDCR exhibits aggregation-enhanced ROS especially less oxygen-dependent hydroxyl radical (HO•- , type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near-infrared fluorescence and massive singlet oxygen and HO•- generation under direct X-ray irradiation, which demonstrate excellent antitumor X-PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1 O2 and radicals (HO•- ) in response to direct X-ray irradiation, which shall provide new insights for designing organic scintillators with excellent X-ray harvesting and predominant free radical generation for efficient X-PDT.

Emodin‐Based Nanoarchitectonics with Giant Two‐Photon Absorption for Enhanced Photodynamic Therapy

AbstractTwo‐photon‐excited photodynamic therapy (TPE‐PDT) has significant advantages over conventional photodynamic therapy (PDT). However, obtaining easily accessible TPE photosensitizers (PSs) with high efficiency remains a challenge. Herein, we demonstrate that emodin (Emo), a natural anthraquinone (NA) derivative, is a promising TPE PS with a large two‐photon absorption cross‐section (TPAC: 380.9 GM) and high singlet oxygen (1O2) quantum yield (31.9 %). When co‐assembled with human serum albumin (HSA), the formed Emo/HSA nanoparticles (E/H NPs) possess a giant TPAC (4.02×107 GM) and desirable 1O2 generation capability, thus showing outstanding TPE‐PDT properties against cancer cells. In vivo experiments reveal that E/H NPs exhibit improved retention time in tumors and can ablate tumors at an ultra‐low dosage (0.2 mg/kg) under an 800 nm femtosecond pulsed laser irradiation. This work is beneficial for the use of natural extracts NAs for high‐efficiency TPE‐PDT.