Cancer Phototherapy Research Articles

Synthesis of gold nano-mushrooms via solvent-controlled galvanic replacement to enhance phototherapeutic efficiency.

In advanced galvanic replacement, variable factors such as the combination of two elements where actual redox reaction and post-synthetic structural transformation take place. Research on manufacturing distinctive nanostructures has mainly focused on the shape of the sacrificial nanotemplate, the presence or absence of additives, and the reaction temperature. Here, we have attempted to confirm the dependency on the solvent, which was considered to simply serve as a medium for a homogeneous chemical reaction to proceed by aiding the dispersion of the nanotemplate and reactants. Thus, we obtained mushroom-like Au nanoplates (mAuNPs) by comprehensive galvanic replacement reaction between solvents, additives, and adsorbents. The mAuNPs with a porous Au nanoplate head and a hollow nanotube tail structure were formed via an optimization process in a 50 v/v% solvent comprising water and ethylene glycol. As a result of confirming the galvanic replacement in co-solvent conditions, in which various types of water miscible solvents were introduced, it was revealed that the most critical factors for regulating the surface polymeric environment of the nanoplate were the relative polarity index of the co-solvent and the hydrogen bonding type. These depend on the molecular structure of the solvent. The manufactured mAuNPs exhibited excellent absorbance in the near-infrared region, and efficient photothermal (PT) conversion-mediated heat dissipation under local laser irradiation. These results confirm the viability of the gene-thermo dual-modal combinatorial cancer therapy based on the surface loading of oligonucleotides and peptides, and the PT therapeutic approach in vitro and in vivo.

Single-molecule photosensitizers for NIR-II fluorescence and photoacoustic imaging guided precise anticancer phototherapy.

It is ideal yet challenging to achieve precise tumor targeting and high-quality imaging guided combined photodynamic and photothermal therapy (PDT and PTT). In this study, we synthesized a series of D–π–A-type single-molecule photosensitizers (CyE-TT, CyQN-TT, and CyQN-BTT) based on quaternized 1,1,2-trimethyl-1H-benz[e]indoles as acceptors by introducing π-bridges to elongate their emission wavelength and triphenylamine as a donor to construct a twisted molecular conformation. We found that the 1O2 generation ability and the photothermal conversion efficiency (PCE) are directly correlated with the π-bridge between donors and acceptors in these molecules. When a 2,1,3-benzothiadiazole group as a π-bridge was introduced into CyQN-BTT, the singlet oxygen yield enhanced to 27.1%, PCE to 37.8%, and the emission wavelength was red-shifted to near-infrared II (NIR-II). Importantly, double-cationic CyQN-BTT displays structure-inherent cancer cell targeting ability instead of targeting normal cells. Consequently, relying on NIR-II fluorescence imaging (NIR-II FLI) and photoacoustic imaging (PAI) guided PDT and PTT, CyQN-BTT can accurately locate solid tumors in mice and effectively eliminate them with good biocompatibility and biosafety to normal tissues. This study provides insights into the design and development of a tumor-specific targeting multifunctional photosensitizer for precise cancer phototherapy.

Geometrical Source Modeling of 6mv Flattening-Filter-Free (Fff) Beam from Truebeam Linear Accelerator and Commissioning Validation Using Monte Carlo Simulation Approach for Cancer Phototherapy

Geometrical Source Modeling of 6mv Flattening-Filter-Free (Fff) Beam from Truebeam Linear Accelerator and Commissioning Validation Using Monte Carlo Simulation Approach for Cancer Phototherapy

Mesoporous polydopamine-based multifunctional nanoparticles for enhanced cancer phototherapy

Cancer phototherapy has attracted increasing attention for its effectiveness, relatively low side effect, and noninvasiveness. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has been shown to exhibit promising prospects in cancer treatment. However, the tumor hypoxia, high level of intracellular glutathione (GSH), and insufficient photosensitizer uptake significantly limit the PDT efficacy. In this work, we combine oxygen supply, GSH depletion, and tumor targeting in one nanoplatform, folate-decorated mesoporous polydopamine nanoparticles (FA-MPPD) co-loaded with new indocyanine green (IR-820) and perfluorooctane (PFO) (IR-820/PFO@FA-MPPD), to overcome the PDT resistance for enhanced cancer PDT/PTT. IR-820/PFO@FA-MPPD exhibit efficient singlet oxygen generation and photothermal effect under 808 nm laser irradiation, GSH-promoted IR-820 release, and efficient cellular uptake, resulting in high intracellular reactive oxygen species (ROS) level under 808 nm laser irradiation and strong photocytotoxicity in vitro. Following intratumoral injection, IR-820/PFO@FA-MPPD can relieve tumor hypoxia sustainably by PFO-mediated oxygen transport and deplete intracellular GSH by the Michael addition reaction, which boost the PDT effect and lead to the most potent antitumor effect upon 808 nm laser irradiation. The multifunctional IR-820/PFO@FA-MPPD developed in this work offer a relatively simple and effective strategy to potentiate PDT for efficient cancer phototherapy.

Graphene Oxide-Gold Nanorods Nanocomposite-Porphyrin Conjugate as Promising Tool for Cancer Phototherapy Performance.

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy.

A Tumor-Targeting Near-Infrared Heptamethine Cyanine Photosensitizer with Twisted Molecular Structure for Enhanced Imaging-Guided Cancer Phototherapy.

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.

Phthalocyanine and Its Formulations: A Promising Photosensitizer for Cervical Cancer Phototherapy.

Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.

Recent Advances in Gold Nanorods‐Based Cancer Theranostics

Cancer Theranostics In article number 2100029, Peng Huang and co-workers provide a periodic update and emphasize on the potential applications of gold nanorods (GNRs) in diagnosis, cancer phototherapy, synergistic tumor therapy, and imaging-guided therapy. The most recent advances in GNRs research towards cancer theranostics are highlighted.

Can Nanoparticles in Homeopathic Remedies Enhance Phototherapy of Cancer? A Hypothetical Model.

The continuous rise in cancer incidence places a massive burden on the health sector to increase efforts in the fight against cancer. As a holistic complementary medicine modality, homeopathy has the potential to assist in the supportive and palliative treatment of cancer patients. Recent empirical studies demonstrate the presence of silica and original source nanoparticles in ultra-high dilutions of several homeopathic medicines. Recent studies have also demonstrated the efficacy of phototherapy in inducing the ablation of cancer cells through laser-activated nanoparticle photosensitizers. A new hypothetical research model is presented herein, in an attempt to investigate and compare the phototherapeutic effects of homeopathic source nanoparticles with photosensitizing nanoparticle agents that have previously been tested.

Biocompatible Mesoporous Silica-Polydopamine Nanocomplexes as MR/Fluorescence Imaging Agent for Light-Activated Photothermal-Photodynamic Cancer Therapy In Vivo.

Conventional cancer phototherapy with single modality suffers from low therapeutic efficacy and undesired posttreatment damage for adjacent normal tissues. Therefore, the lower NIR laser irradiation power is vital to the reduction or preclusion of risk of scalds and burns in normal tissues. Herein, we rationally proposed a novel multifunctional nanocomplex, which enabled good magnetic resonance (MR) imaging contrast effect and promising photothermal conversion efficacy. The prepared core/shell nanocomplexes [MSN-Ce6@PDA (Mn)] were composed of chlorin e6-embedded mesoporous silica/nanoparticle composites as the cores, and then polydopamine and manganese ions were conjugated on the cores to form protective shells. The MSN-Ce6@PDA (Mn) nanocomplexes revealed superior properties in colloidal stability, photothermal conversion, reaction oxygen species generation, magnetic resonance imaging, etc. Under the guidance of MR and fluorescence imaging, these MSN-Ce6@PDA (Mn) nanocomplexes were found to be primarily accumulated in the MDA-MB-231 tumor area. Furthermore, the combined photodynamic and photothermal therapy exhibited strong inhibition to the growth of MDA-MB-231 tumor in vitro and in vivo. Besides, the MSN-Ce6@PDA (Mn) nanocomplexes also exhibited excellent biocompatibility and low damage to the healthy animals. Hence, the results demonstrated that the prepared MSN-Ce6@PDA (Mn) nanocomplex would be a promising potential for multimodal imaging-guided phototherapy.

Gold and Carbon-Based Nano-theranostics: An Overview on the Developments and Applications for Cancer Phototherapy.

Nano-theranostics (NTs) are versatile nanomaterials, explored in the current scenario of cancer therapy. A nano-theranostic material alone can diagnose and generate a therapeutic effect. Various materials have been explored for their NT action like gold and carbon-based material. The photon-based cancer theranostics has grabbed the attention of researchers due to their localized and trigger activated effect. NTs have shown a promising result in pre-clinical and clinical studies. The current review illustrates the meticulous efforts conducted by researchers across the globe to innovate and explore the photon-based cancer NT platforms of gold and carbon with their application in cancer therapy.

Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a cancer phototherapy that uses antibody-IR700 conjugate (Ab-IR700) and NIR light. Ab-IR700 forms aggregates on the plasma membranes of targeted cancer cells after light exposure, inducing lethal physical damage within the membrane. Low-molecular-weight (LMW) ligands are candidate targeting moieties instead of antibodies, but whether LMW-IR700 conjugates induce cell death by aggregation, the same mechanism as Ab-IR700, is unknown. Thus, we investigated differences in cytotoxicity and mechanisms between LMW-IR700 and Ab-IR700 targeting prostate-specific membrane antigen (PSMA). Both conjugates decreased cell viability to the same degree after light irradiation, but different morphological changes were observed in PSMA-positive LNCaP cells by microscopy. Cell swelling and bleb formation were induced by Ab-IR700, but only swelling was observed in cells treated with LMW-IR700, suggesting the cells were damaged via different cytotoxic mechanisms. However, LMW-IR700 induced bleb formation, a hallmark of NIR-PIT with Ab-IR700, when singlet oxygen was quenched or LMW-IR700 was localized only on the plasma membrane. Moreover, the water-soluble axial ligands of LMW-IR700 were cleaved, consistent with previous reports on Ab-IR700. Thus, the main cytotoxic mechanisms of Ab-IR700 and LMW-IR700 differ, although LMW-IR700 on the plasma membrane can cause aggregation-mediated cytotoxicity as well as Ab-IR700.

Synergistic therapeutic strategies for cancer treatment based on nanophototherapy

Abstract Treatment of malignant tumors has always been a worldwide challenge. The complexity, diversity, and heterogeneity of tumors have prompted the treatment strategies to gradually shift from monotherapy to combination therapy that can synergize multiple treatment modalities. With unique physical and chemical properties, nanomaterials have been widely used in different cancer therapies, including chemotherapy, immunotherapy, and phototherapy. Especially, the variability and integrity of nanomaterials make them ideal media for synergistic collaboration strategies. Here, we provide our perspective on the synergistic strategy of nanoplatform-mediated phototherapies and related combination therapies, specifically photochemotherapy, photoradiotherapy, and photoimmunotherapy. Besides, we provide an analysis and outlook on the current challenges faced by synergistic nanophototherapy.

Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy.

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)–ZW800-1 conjugate (INH–ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH–ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH–ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH–ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.

Recent Advances in Gold Nanorods‐Based Cancer Theranostics

Gold nanorods (GNRs) with a unique localized surface plasmon resonance (LSPR) property have shown groundbreaking performance in catalysis, sensing, and biomedical applications. Intrinsic inertness, biocompatibility, a tunable longitudinal LSPR band in the near‐infrared (NIR)‐I/II region, high extinction coefficient, and remarkable optical properties all make GNRs excellent photothermal (PT) nanoagents, photosensitizers, and imaging contrast agents for drug delivery, cancer phototherapy, and multimodal imaging‐guided cancer therapy. In this periodic update, bottom–up fabrication of long and short GNRs by seed‐mediated and seedless methods is reviewed, with elaboration concerning the tuning of LSPR band and the generation of localized hyperthermia via light to heat conversion. Recent advances in applications of GNR research in bioimaging, therapy, and theranostics of cancer are then reviewed. Unmet challenges and critical points are discussed with focus given to translation from bench to clinic.

Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer.

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.

Semiconductor small molecule IHIC/ITIC applied to photothermal therapy and photoacoustic imaging of tumors.

Organic semiconductor small molecules IHIC and ITIC have been developed as solar cell materials, and because of their strong near-infrared absorption capabilities, they are promising for cancer phototherapy. This article reports the application of semiconductor small molecule IHIC/ITIC liposomes in photothermal therapy and photoacoustic imaging of tumors firstly. Experiments show that the liposome-loaded IHIC/ITIC material has good biocompatibility and can be effectively enriched in tumor sites. After being irradiated with laser, it can emit strong photoacoustic signals, and has achieved good results in the photothermal treatment of breast cancer mice. We believe that organic semiconductor small molecule IHIC/ITIC will become a promising photothermal agent with wonderful development possibilities.

Cell Membrane-Coated Halloysite Nanotubes for Target-Specific Nanocarrier for Cancer Phototherapy.

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.

Thermal-triggered packing of lipophilic NIR dye IR780 in hepatitis B core at critical ionic strength and cargo-host ratio for improved stability and enhanced cancer phototherapy

Virus-like particles (VLPs) holding internal cavity with diameter from tens up to one hundred nanometers are attractive platform for drug delivery. Nevertheless, the packing of drugs in the nanocage mainly relies on complicated disassembly-reassembly process. In this study, hepatitis B core protein (HBc) VLPs which can withstand temperature up to 90 °C was employed as carrier to load a lipophilic near infrared dye IR780. It was found that an attaching-dis-atching-diffusing process was involved for the entering of IR780 in the cavity of HBc. The first two steps were associated with the electrostatic interactions between oppositely charged HBc and IR780, which was critically manipulated by ionic strength and HBc/IR780 mass ratio at which they were mixed; while the diffusion of IR780 across the shell of HBc showed a temperature-dependent manner that can be triggered by thermal induced pore-opening of the HBc capsid. At optimized condition, about 1055 IR780 molecules were encapsulated in each HBc by simply mixing them for 10 min at 60 °C. Compared with free IR780, the HBc-IR780 particles showed significantly improved aqueous and photostability, as well as enhanced photothermal and photodynamic performance for cancer therapy. This study provides a novel drug loading strategy and nanomemedicine for cancer phototherapies.

Supramolecular micelles as multifunctional theranostic agents for synergistic photodynamic therapy and hypoxia-activated chemotherapy

Photodynamic therapy (PDT), where a photosensitizer (under light irradiation) converts molecular oxygen to singlet oxygen to elicit programmed cell death, is a promising cancer treatment modality with a high temporal and spatial resolution. However, only limited cancer treatment efficacy has been achieved in clinical PDT due to the hypoxic conditions of solid tumor microenvironment that limits the generation of singlet oxygen, and PDT process often leads to even more hypoxic microenvironment due to the consumption of oxygens during therapy. Herein, we designed novel supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles (CPC) were derived from a polyethylene glycol (PEG) system dually tagged with hydrophilic cucurbit[7]uril (CB[7]) and hydrophobic Chlorin e6 (Ce6), respectively on each end, for synergistic antitumor therapy via PDT of Ce6 and chemotherapy of a hypoxia-responsive prodrug, banoxantrone (AQ4N), loaded into the cavity of CB[7]. In addition, CPC was further modularly functionalized by folate (FA) via strong host-guest interaction between folate-amantadine (FA-ADA) and CB[7] to produce a novel nanoplatform, AQ4N@CPC-FA, for targeted delivery. AQ4N@CPC-FA exhibited enhanced cellular uptake, negligible cytotoxicity and good biocompatibility, and improved intracellular reactive oxygen species (ROS) generation efficiency. More importantly, in vivo evaluation of AQ4N@CPC-FA revealed a synergistic antitumor efficacy between PDT of Ce6 and hypoxia-activated chemotherapy of AQ4N (that can be converted to chemotherapeutic AQ4 for tumor chemotherapy in response to the strengthened hypoxic tumor microenvironment during PDT treatment). This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment, but also offers important new insights to design and development of multifunctional supramolecular drug delivery system. Statement of significancePhotodynamic therapy (PDT) has exhibited a variety of advantages for cancer phototherapy as compared to traditional chemotherapy. However, the unsatisfactory therapeutic efficacy by PDT alone as a result of the enhanced tumor hypoxia during PDT has limited its clinical application. Herein, we designed multifunctional supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles are biocompatible and possess strong red absorption, controlled drug release profile, and ultimately enhanced therapeutic outcome via PDT-chemotherapy. This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment of cancer, but also offers important new insights to design and development of multifunctional supramolecular drug delivery tool for multi-modality cancer therapy.