Cancer Phototherapy Research Articles

A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis.

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1H,1H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

Stimuli-responsive Graphene-Polysaccharide Nanocomposites for Drug Delivery and Tissue Engineering

Abstract:: Natural polysaccharide-based nanoparticles are known for their non-toxic nature and diverse medical applications. Graphene oxide (GO) nanoparticles show potential in cancer treat-ment due to their ability to target medication delivery and influence ROS generation. These nanocomposites are versatile in gene transport, therapy, and photodynamic therapy, especially when surface-modified. Proper dispersion and functionalization of GO in polymer matrices are crucial, with examples like hyaluronic acid-functionalized GO offering versatile platforms for cancer drug administration. The potential of graphene oxide extends to cancer phototherapy, electronic nanowires, hydrogels, antibacterial nanocomposites, and environmental applications. When activated by polysaccharides, graphene-based nanocomposites exhibit anti-inflammatory and anticancer properties, making them valuable across various industries, including water treat-ment.

Nanoscale Evaluation of the Degradation Stability of Black Phosphorus Nanosheets Functionalized with PEG and Glutathione-Stabilized Doxorubicin Drug-Loaded Gold Nanoparticles in Real Functionalized System.

Two-dimensional black phosphorus (2D BP) has attracted significant research interest in the field of biomedical applications due to its unique characteristics, including high biocompatibility, impressive drug-loading efficiency, phototherapeutic ability, and minimal side effects. However, its puckered honeycomb lattice structure with lone-pair electrons of BP leads to higher sensitivity and chemical reactivity towards H2O and O2 molecules, resulting in the degradation of the structure with physical and chemical changes. In our study, we synthesize polyethylene glycol (PEG) and glutathione-stabilized doxorubicin drug-assembled Au nanoparticle (Au-GSH-DOX)-functionalized BP nanosheets (BP-PEG@Au-GSH-DOX) with improved degradation stability, biocompatibility, and tumor-targeting ability. Transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy indicate the nanoscale degradation behavior of synthesized nanoconjugates in three different environmental exposure conditions, and the results demonstrate the remarkable nanoscale stability of BP-PEG@Au-GSH-DOX against the degradation of BP, which provides significant interest in employing 2D BP-based nanotherapeutic agents for tumor-targeted cancer phototherapy.

Sterically Twisted Mitochondria‐Targeting Photosensitizers for Augmented Near‐Infrared II Fluorescence‐Guided Photodynamic Immunotherapy

AbstractNear‐infrared (NIR) fluorescent mitochondria‐targeting photosensitizers (PSs) hold great potential for efficient image‐guided cancer phototherapy, but it remains challenging to develop PSs concurrently integrating high‐contrast NIR‐II fluorescence imaging and efficient therapeutic capabilities. Herein, a heptamethine cyanine (HCy) PS (termed I2HCy‐TPE nanoparticles (NPs)) by a molecular engineering strategy combining the heavy atom effect and structural distortion is reported. The heavy atom iodine is introduced to boost the intersystem crossing process, and the bulky tetraphenylethylene (TPE) moiety placed at the meso‐position of the heptamethine chain creates a highly distorted conformation in I2HCy‐TPE, theoretically verified by density functional theory calculations. This strategy synergistically promotes the 1O2 generation efficiency and assure the strong NIR fluorescence emission in aggregated states. Combining with the intrinsic mitochondria‐targeting capability, I2HCy‐TPE NPs are able to cause mitochondria‐targeted damage of cancer cells via the PDT and immunogenetic cell death‐triggered immune responses under NIR laser irradiation. In vivo experiments demonstrate that the biocompatible I2HCy‐TPE NPs present exceptional capability for in vivo NIR‐II fluorescence bioimaging of whole‐body and blood vessels, and exert efficient NIR‐II fluorescence‐guided photodynamic immunotherapy against triple‐negative breast cancer.

Carbon Dots an Integrative Nanostructure for Fluorescent Bio-imaging, Targeted Delivery of Medication and Phototherapy in Malignancy: A Review

Background: Silent onset and metastasis in tissues make cancer the most devastating illness globally. Monitoring the growth of the tumour and delivering drugs to specific tissues are some of the major issues associated with treatment. However, with an improved understanding of tumour microenvironments and advancements in nanocarriers of drugs, novel nano-targeting pathways that can be utilised by nanocarriers have been developed. Carbon Dots, with their tiny size and outstanding physicochemical features, are an emerging category of carbon nanostructures that have attracted a lot of curiosity. Objective: Multitudinous attempts and extensive studies have been undertaken by many researchers regarding the synthesis of Carbon Dots and their applications in various fields. These studies have explained that the synthesised Carbon Dots have versatile surface functionalities, high luminescence, and excellent biocompatibility. This article focuses on recent developments in synthesis approaches, carbon precursors used, and applications of Carbon Dots, specifically within the biomedical field, with a particular focus on cancer. Results: Carbon dots synthesised from a variety of precursors can act as prominent candidates for bioimaging and drug carriers and are used in cancer phototherapy. In this article, Carbon Dots are summarised based on their bright luminescent properties, distinct structure, drug loading capacity, and near-infrared (NIR) emission. Conclusion: Carbon dots, employed as tumour theranostics, can serve as an alternative to synthetic fluorescent dyes. They fulfil the role of bioimaging agents and facilitate the precise delivery of drugs to cancer cells. Additionally, they exhibit excellence as phototherapeutic agents, featuring high nearinfrared (NIR) emission and minimal side effects.

Near-Infrared Light-Driving Organic Photothermal Agents with an 88.9% Photothermal Conversion Efficiency for Image-Guided Synergistic Phototherapy.

Photothermal agents (PTAs) with desirable near-infrared (NIR) absorption and excellent photothermal conversion efficiency (PCE) are ideal candidates for cancer treatment. However, numerous PTAs still require high-intensity and long-duration laser irradiation to completely ablate the tumor during the photothermal therapy (PTT) process, resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating intense NIR absorption and high PCE into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, a series of donor-acceptor type PTAs (CC1 to NC4) are designed through a molecular engineering strategy. Theoretical calculations and experimental results show that the NIR absorption and photothermal effect from CC1 to NC4 are significantly enhanced as expected. Notably, NC4 nanoparticles exhibit intense NIR absorption, superhigh PCE of up to 88.9% for PTT, photoacoustic imaging and photothermal imaging, and effective reactive oxygen species generation for photodynamic therapy (PDT). The superior PTT/PDT synergistic phototherapeutic efficacy is well demonstrated by the complete elimination of tumor in vivo upon one-time, low-intensity, and short-duration laser irradiation (808nm, 330mW cm-2, and 3min). This work provides a valuable guideline for rational design of PTAs for cancer phototherapy.

Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy.

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g-1 cm-1 at 808nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.

Tumor-Targeted Squaraine Dye for Near-Infrared Fluorescence-Guided Photodynamic Therapy.

Many efforts have been made to develop near-infrared (NIR) fluorescent dyes with high efficiency for the NIR laser-induced phototherapy of cancer. However, the low tumor targetability and high nonspecific tissue uptake of NIR dyes in vivo limit their applications in preclinical cancer imaging and therapy. Among the various NIR dyes, squaraine (SQ) dyes are widely used due to their high molar extinction coefficient, intense fluorescence, and excellent photostability. Previously, benzoindole-derived SQ (BSQ) was prepared by incorporating carboxypentyl benzoindolium end groups into a classical SQ backbone, followed by conjugating with cyclic RGD peptides for tumor-targeted imaging. In this study, we demonstrate that the structure-inherent tumor-targeting BSQ not only shows a high fluorescence quantum yield in serum but also exhibits superior reactive oxygen species (ROS) generation capability under the 671 nm laser irradiation for effective photodynamic therapy (PDT) in vitro and in vivo. Without targeting ligands, the BSQ was preferentially accumulated in tumor tissue 24 h post-injection, which was the optimal timing of the laser irradiation to induce increments of ROS production. Therefore, this work provides a promising strategy for the development of photodynamic therapeutic SQ dyes for targeted cancer therapy.

Single‐Cell RNA‐Sequencing‐Aided Covalent Organic Frameworks‐Based Microneedle Design Targeting Phototherapy Resistant Tumor Cell

AbstractCovalent organic frameworks (COFs) exhibit immense potential for phototherapy due to their exceptional light absorption, photostability, and biocompatibility. Nevertheless, tumor cells can develop resistance to phototherapy after an initial response, posing a significant challenge for complete eradication. In this study, a COF‐based photosensitizer, TCN‐PPDA‐COF, is designed with outstanding photothermal properties and delivered to tumors using microneedles (MN) to enhance cancer phototherapy. Single‐cell RNA‐sequencing (scRNA‐seq) technology is then utilized to explore the mechanisms underlying tumor cell adaptation to COF‐mediated phototherapy. The scRNA‐seq analysis revealed that phototherapy‐resistant tumor cells displayed elevated expression of HIF‐1α and VEGF signaling pathways, fostering intratumoral angiogenesis and facilitating their continued survival during phototherapy. In response to this phenomenon, a unique CA‐microneedle (MN) patch is developed, tailored for co‐delivering TCN‐PPDA‐COF and angiogenesis inhibitors AL3818 to the tumor site. The CA‐MN patches can effectively inhibit angiogenesis in tumors while mediating phototherapy, thereby obliterating the phototherapy‐resistant tumor cells. In 4T1 tumor‐bearing mouse model, the CA‐MN patches achieved nearly complete regression of tumor grafts and activated host anti‐tumor immunity, thereby enhancing the response rate of αPD‐1 and effectively restraining tumor metastasis and recurrence. This study underscored an ingenious approach to modify COF‐MN patches through scRNA‐seq technology.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm−2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 μg mL−1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 μg mL−1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 μg mL−1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.

The application of peroxidase mimetic nanozymes in cancer diagnosis and therapy

In recent decades, scholarly investigations have predominantly centered on nanomaterials possessing enzyme-like characteristics, commonly referred to as nanozymes. These nanozymes have emerged as viable substitutes for natural enzymes, offering simplicity, stability, and superior performance across various applications. Inorganic nanoparticles have been extensively employed in the emulation of enzymatic activity found in natural systems. Nanoparticles have shown a strong ability to mimic a number of enzyme-like functions. These systems have made a lot of progress thanks to the huge growth in nanotechnology research and the unique properties of nanomaterials. Our presentation will center on the kinetics, processes, and applications of peroxidase-like nanozymes. In this discourse, we will explore the various characteristics that exert an influence on the catalytic activity of nanozymes, with a particular emphasis on the prevailing problems and prospective consequences. This paper presents a thorough examination of the latest advancements achieved in the domain of peroxidase mimetic nanozymes in the context of cancer diagnosis and treatment. The primary focus is on their use in catalytic cancer therapy, alongside chemotherapy, phototherapy, sonodynamic therapy, radiation, and immunotherapy. The primary objective of this work is to offer theoretical and technical assistance for the prospective advancement of anticancer medications based on nanozymes. Moreover, it is anticipated that this will foster the investigation of novel therapeutic strategies aimed at achieving efficacious tumor therapy.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. Statement of significanceThrough the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron–hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Progress of cell membrane-derived biomimetic nanovesicles for cancer phototherapy.

In recent years, considerable attention has been given to phototherapy, including photothermal and photodynamic therapy to kill tumor cells by producing heat or reactive oxygen species (ROS). It has the high merits of noninvasiveness and limited drug resistance. To fully utilize this therapy, an extraordinary nanovehicle is required to target phototherapeutic agents in the tumor cells. Nanovesicles embody an ideal strategy for drug delivery applications. Cell membrane-derived biomimetic nanovesicles represent a developing type of nanocarrier. Combining this technique with cancer phototherapy could enable a novel strategy. Herein, efforts are made to describe a comprehensive overview of cell membrane-derived biomimetic nanovesicles for cancer phototherapy. The description in this review is mainly based on representative examples of exosome-derived biomimetic nanomedicine research, ranging from their comparison with traditional nanocarriers to extensive applications in cancer phototherapy. Additionally, the challenges and future prospectives for translating these for clinical application are discussed.

Thiophene assisted cellular uptake enhancement for highly efficient NIR-II cancer phototheranostics.

We designed two series of NIR-II PTAs with D-A or D-A-D structures, in which the introduction of thiophene promotes a bathochromic shift of emission into the NIR-II region, helps to improve the cellular uptake of the PTAs and facilitates NIR-II imaging-guided PDT/PTT cancer phototherapy.

Cancer phototherapy by CO releasing terpyridine-based Re(I) tricarbonyl complexes via ROS generation and NADH oxidation.

Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)3(ph-tpy)Cl] (Retp1), [Re(CO)3(an-tpy)Cl] (Retp2), and [Re(CO)3(py-tpy)Cl] (Retp3) where ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine; an-tpy = 4'-anthracenyl-2,2':6',2″-terpyridine, py-tpy = 4'-pyrenyl-2,2':6',2″-terpyridine. The structures of Retp1 and Retp2 were confirmed from the SC-XRD data, indicating distorted octahedral structures. Unlike traditional PDT agents, these complexes generated reactive oxygen species (ROS) via type I and type II pathways and oxidized redox crucial NADH (reduced nicotinamide adenine dinucleotide) upon visible light exposure. Retp3 showed significant mitochondrial localization and demonstrated photoactivated anticancer activity (IC50 ∼ 2 µM) by inducing ROS-mediated cell death in cancer cells selectively (photocytotoxicity Index, PI > 28) upon compromising mitochondrial function in A549 cells. Their diagnostic capabilities were ultimately assessed using clinically relevant 3D multicellular tumor spheroids (MCTs).

A photoarchitectonic hydrogel for synergistic in vitro chemo–phototherapy of breast cancer

Laser-assisted combinatorial breast cancer treatment using a photoarchitectonic hydrogel shows a synergistic effect.

Choice of Nanoparticles for Theranostics Engineering: Surface Coating to Nanovalves Approach.

Surface engineered nanoparticles (metallic and nonmetallic) have gained tremendous attention for precise imaging and therapeutics of cell/tumors at molecular and anatomic levels. These tiny agents have shown their specific physicochemical properties for early-stage disease diagnosis and cancer theranostics applications (imaging and therapeutics by a single system). For example, gold nanorods (AuNRs) demonstrate better photothermal response and radiodensity for theranostics applications. However, upon near infrared light exposure these AuNRs lose their optical property which is characteristic of phototherapy of cancer. To overcome this issue, silica coating is a safe choice for nanorods which not only stabilizes them but also provides extra space for cargo loading and makes them multifunctional in cancer theranostics applications. On the other hand, various small molecules have been coated on the surface of nanoparticles (organic, inorganic, and biological) which improve their biocompatibility, blood circulation time, specific biodistribution and tumor binding ability. A few of them have been reached in clinical trials, but, struggling with FDA approval due to engineering and biological barriers. Moreover, nanoparticles also face various challenges of reliability, reproducibility, degradation, tumor entry and exit in translational research. On the other hand, cargo carrier nanoparticles have been facing critical issues of premature leakage of loaded cargo either anticancer drug or imaging probes. Hence, various gate keepers (quantum dots to supramolecules) known nanovalves have been engineered on the pore opening of the cargo systems. Here, a review on the evolution of nanoparticles and their choice for diagnostics and therapeutics applications has been discussed. In this context, basic requirements of multifunctional theranostics design for targeted imaging and therapy have been highlighted and with several challenges. Major hurdles experienced in the surface engineering routes (coating to nanovalves approach) and limitations of the designed theranostics such as poor biocompatibility, low photostability, non-specific targeting, low cargo capacity, poor biodegradation and lower theranostics efficiency are discussed in-depth. The current scenario of theranostics systems and their multifunctional applications have been presented in this article.

Single laser activated photodynamic/photothermal cancer therapy using a single mitochondria-targeted phototherapeutic agent with aggregation-induced emission characteristics

OPTM as an efficient mitochondria-targeted agent can be successfully employed for the synergistic cancer phototherapy under single laser irradiation.