Cancer Phototherapy Research Articles

Violet Phosphorus Nanosheet: A Biocompatible and Stable Platform for Stimuli-Responsive Multimodal Cancer Phototherapy.

As a functional 2D material, black phosphorus (BP) has garnered wide attention from many researchers in recent years. BP has a wide NIR absorption window and is a promising candidate for cancer phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT). However, due to its rapid degradation and short shelf-life in conventional water, the application of BP in the field of cancer therapy is limited. Violet phosphorus (VP), the more stable allotrope of phosphorus, has not yet been investigated for its function and biological application. In this study, VP nanosheets are successfully fabricated by liquid-phase exfoliation and demonstrated that their shelf-life in deionized water could be as long as 10 days, which is much longer than that of BP. Through in vivo and in vitro experiments, the PDT, PTT, and catalytic therapeutic effects of VP, as well as its excellent biosafety for the first time are shown. VP effectively inhibits tumor growth without causing major side effects. The current study provides new ideas and strategies for the biological application of 2D sheets of phosphorus isotope and lays the foundation for further studies on exploring the biomedical application of phosphorus isotopes.

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Poly(2-ethyl-2-oxazoline)-IR780 conjugate nanoparticles for breast cancer phototherapy.

Aims: To address the limitations of IR780 by preparing hydrophilic polymer-IR780 conjugates and to employ these conjugates in the assembly of nanoparticles (NPs) intended for cancer photothermal therapy. Materials & methods: The cyclohexenyl ring of IR780 was conjugated for the first time with thiol-terminated poly(2-ethyl-2-oxazoline) (PEtOx). This novel poly(2-ethyl-2-oxazoline)-IR780 (PEtOx-IR) conjugate was combined with D-α-tocopheryl succinate (TOS), leading to the assembly of mixed NPs(PEtOx-IR/TOSNPs). Results: PEtOx-IR/TOS NPs displayed optimal colloidal stability as well as cytocompatibility in healthy cells at doses within the therapeutic range. In turn, the combination of PEtOx-IR/TOS NPs and near-infrared light reduced heterotypic breast cancer spheroid viability to just 15%. Conclusion: PEtOx-IR/TOS NPs are promising agents for breast cancer photothermal therapy.

Conjugates of lactobionic acid and IR820: New photosensitizers for efficient photodynamic therapy of hepatoma cells.

New indocyanine green (IR820) is an indocyanine green analog which has attracted increasing attention in cancer phototherapy for the prominent absorbance at near-infrared region and improved stability. However, the lack of tumor targeting ability is still an obstacle that severely limits the application of IR820. Lactobionic acid (LA) is a ligand for the asialoglycoprotein receptors which are overexpressed on the membrane of hepatocellular carcinoma cells. In this work, three conjugates of LA and IR-820, namely LA-IR820, LA-SS-IR820, and LA-DEG-IR820, were developed for targeted photodynamic therapy of hepatocellular carcinoma (HCC). The in vitro photodynamic effect study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit similar singlet oxygen quantum yield as compared to free IR820. The cellular uptake study demonstrates that LA-IR820, LA-SS-IR820, and LA-DEG-IR820 exhibit enhanced cellular uptake amount as compared to free IR820 due to the ligand-receptor interactions between LA and asialoglycoprotein receptor overexpressed on the membrane of HepG2 cells. Among these three conjugates, LA-IR820 with hydrodynamic diameter of 154.6 ± 6.1 nm exhibits the highest cellular uptake amount. The cellular reactive oxygen species (ROS) generation study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 display enhanced cellular ROS level as compared to free IR820 and LA-IR820 exhibits the highest cellular ROS level upon 600 mW/cm2 660 nm laser irradiation. As a result, LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit enhanced photocytotoxicity against HepG2 cells as compared to free IR820 and LA-IR820 exhibits the highest photocytotoxicity. LA-IR820, LA-SS-IR820, and LA-DEG-IR820 show significant potential for the targeted photodynamic therapy of HCC.

Injectable Carbon Dots-Based Hydrogel for Combined Photothermal Therapy and Photodynamic Therapy of Cancer.

Hydrogel has been widely used in modern biotherapeutics due to its excellent biocompatibility, degradability, and high drug loading capacity. Among them, the construction of a phototherapy system including photosensitizer and hydrogel has aroused great interest in tumor therapy. Unfortunately, complex modifications are necessary to integrate different photosensitizers into the hydrogel. In this work, an injectable hydrogel was proposed by the Schiff base reaction between HA-CHO and carbon dots (CDs), which can realize PTT and PTT simultaneously. Notably, the CDs with rich -NH2 can be used not only as a photosensitizer but also as an efficient cross-linking agent for the Schiff base reaction to form a hydrogel network. The CD@Hydrogel with outstanding biosafety showed a high antitumor effect after 660 nm laser irradiation in in vitro and in vivo experiments. In summary, the CD@Hydrogel can not only realize PTT and PDT synergistic treatment under one light source but also act as a cross-linking agent to react with HA-CHO to form hydrogel, which is simple and efficient, providing a new strategy for cancer phototherapy.

Application of photo-responsive metal-organic framework in cancer therapy and bioimaging

Metal-organic frameworks (MOFs) are a class of hybrid porous crystalline materials that are assembled with metal ions/clusters and organic linkers. The fungibility of organic ligands and metal centers endow MOFs that are easy to design and synthesize. Based on their unique structure, multifarious MOFs with diverse functionalities have recently been widely applied in various research areas. Particularly striking is the application of photo-responsive MOFs in biological sensing and imaging. Notably, the photoelectronic properties make photo-responsive MOFs an ideal platform for cancer phototherapy. Moreover, ultrahigh porosities and tunable pore sizes allow MOFs to load anticancer drugs, further enhancing the antitumor efficiency. In this review, the categories and developing strategies of MOFs are briefly introduced. The application fields of MOFs in bioimaging, such as up-conversion fluorescence imaging, single/two-photon fluorescence bioimaging, magnetic resonance imaging, etc., are summarized. The working mechanism of MOFs in photo-responsive, photothermal therapy (PTT), and photodynamic therapy (PDT) are expounded. Examples of using MOFs for cancer treatment, including PTT, PDT, chemotherapy, and radiotherapy, are also demonstrated. Lastly, current limitations, challenges, and future perspectives for bioimaging and cancer treatment of MOFs are discussed. We believe that the versatile MOF will bring the dawn to the next generation of cancer treatment.

Organic Theranostic Nanoplatform with Enhanced Fluorescence and Singlet Oxygen Quantum Yield for Tumor-Targeting Image-Guided Photodynamic/Photothermal Synergistic Therapy

The development of biocompatible therapeutic agents to achieve tumor-targeting photothermal/photodynamic synergistic therapy under imaging guidance is crucial for effective cancer phototherapy. Herein, we elaborately designed an organic theranostic nanoplatform, Ce6@HA-Cys-TTDTT nanoparticles (NPs), in which the active targeting moiety hyaluronic acid (HA) was conjugated with a hydrophobic conjugated oligomer TTDTT through the side chain of cystamine (Cys) to form an amphiphilic polymer, and then an excellent photosensitizer chlorin e6 (Ce6) was encapsulated by self-assembly. Bithiophenyl diketopyrrolopyrrole (TDPP) and triphenylamine were utilized as the acceptor (A) and donor (D), respectively, to construct the D–A–D molecule TTDTT, which served as an excellent photothermal agent with a moderate 1O2 quantum yield and quenched fluorescence (FL) in HA-Cys-TTDTT NPs. However, Ce6@HA-Cys-TTDTT NPs exhibited obviously higher 1O2 quantum yields (ΦΔ = 53.0%) and FL intensity than HA-Cys-TTDTT NPs (ΦΔ = 29.6%) and free Ce6 under laser irradiation at 635 nm and still maintained a high photothermal conversion efficiency (η = 37.7%). These results may be attributed to the efficient energy transfer from TTDTT to Ce6 in Ce6@HA-Cys-TTDTT NPs and the facilitation of the transition of singlet-to-triplet excited state via an intersystem crossing pathway. Ce6@HA-Cys-TTDTT NPs presented high tumor targeting capability in FL/thermal imaging in vivo and significant advantages over free Ce6 in long-term FL imaging in vivo. The remarkable antitumor efficacy of Ce6@HA-Cys-TTDTT NPs under a single wavelength laser irradiation was confirmed through in vitro and in vivo experiments. In this study, a multifunctional organic theranostic nanoplatform was designed to enhance the effect of tumor phototherapy, benefiting from the tumor-targeting multimodal imaging-guided photodynamic/photothermal synergistic therapy.

A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients’ quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

Dually enhanced phototherapy by gambogic acid and hyperthemia-activated chemotherapy for synergistic breast cancer treatment

Combining chemotherapy and phototherapy (including photodynamic therapy and photothermal therapy) via nanoscale drug delivery systems has been widely explored to improve the therapeutic efficacy of cancers. Nevertheless, deficient reactive oxygen species (ROS) level caused by the excessive antioxidants (e.g., glutathione (GSH)) in tumor cells and thermoresistance mediated by heat shock proteins (HSPs) represent two pivotal obstacles for phototherapy. In addition, limited control on drug release via conventional nanocarriers results in unpredictable side effects of chemotherapeutic drugs. To tackle these problems, a novel phase change material (PCM)-based nanoplatform co-delivering paclitaxel (PTX), IR780 and gambogic acid (GA) was developed via a facile method to achieve chemotherapy synergized by dually-enhanced phototherapy of breast cancers. PCM-based nanoparticles (NPs) revealed favorable particle size and greatly improved photostability of IR780. PCM endowed the NPs with hyperthemia-triggered release of PTX for chemotherapy, which was beneficial to dampen the side effects. Upon the cellular uptake, GA-depleted intracellular GSH and blocked the overexpression of HSP90, which in turn simultaneously increased the ROS level and suppressed thermoresistance to enhance the efficacies of PDT and PTT, respectively. Finally, the dually-energized phototherapy and PTT-activated low-dose PTX-based chemotherapy achieved outstanding antitumor performances in vitro and in vivo. Taken together, via the NIR-activatable PCM-based NPs, a strategy of harnessing a single enhancer to boost the efficacies of dual-modal phototherapy and low-dose chemotherapy has been established for improved cancer treatment and reduced side effects.

Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Tumor Microenvironment Stimuli-Responsive Single-NIR-Laser Activated Synergistic Phototherapy for Hypoxic Cancer by Perylene Functionalized Dual-Targeted Upconversion Nanoparticles.

Although synergistic therapy has shown great promise for effective treatment of cancer, the unsatisfactory therapeutic efficacy of photothermal therapy/photodynamic therapy is resulted from the absorption wavelength mismatch, tumor hypoxia, photosensitizer leakage, and inability in intelligent on‐demand activation. Herein, based on the characteristics of tumor microenvironment (TME), such as the slight acidity, hypoxia, and overexpression of H2O2, a TME stimuli‐responsive and dual‐targeted composite nanoplatform (UCTTD‐PC4) is strategically explored by coating a tannic acid (TA)/Fe3+ nanofilm with good biocompatibility onto the upconversion nanoparticles in an ultrafast, green and simple way. The pH‐responsive feature of UCTTD‐PC4 remains stable during the blood circulation, while rapidly releases Fe3+ in the slightly acidic tumor cells, which results in catalyzing H2O2 to produce O2 and overcoming the tumor hypoxia. Notably, the emission spectrum of the UCTTD perfectly matches the absorption spectrum of the photosensitizer (perylene probe (PC4)) to achieve the enhanced therapeutic effect triggered by a single laser. This study provides a new strategy for the rational design and development of the safe and efficient single near‐infrared laser‐triggered synergistic treatment platform for hypoxic cancer under the guidance of multimodal imaging.

Lactobionic acid-functionalized hollow mesoporous silica nanoparticles for cancer chemotherapy and phototherapy

The combination of chemotherapy and phototherapy has become a promising cancer treatment strategy. In this study, a pH/NIR dual-responsive hollow mesoporous silica nanoparticles (HMSNs) based nanocarrier for co-delivering doxorubicin hydrochloride (DOX) and indocyanine green (ICG) was developed. DOX was loaded for chemotherapy and ICG for photothermal therapy (PTT) and photodynamic therapy (PDT). This system targets the asialoglycoprotein receptor (ASGPR) in over-expressing human hepatocellular liver carcinoma cells (HepG2) by linking HMSNs and lactobionic acid (LA)-modified dialdehyde chitosan (DACS) via Schiff base bonds. It is demonstrated that HMSNs-DACS-LA have been successfully prepared through various physical characterizations. Drug release tests revealed that it had the characteristics of properties of pH/NIR dual-responsive. In vitro cellular uptake and cytotoxicity assay showed that ID@HMSNs-DACS-LA could target HepG2 cells and reduced the activity of tumor cells. Therefore, co-delivery of ICG and DOX via HMSNs-DACS-LA nanocarriers may provide a feasible strategy for tumor-targeted combined chemotherapy and phototherapy.

Near-infrared light and redox dual-activatable nanosystems for synergistically cascaded cancer phototherapy with reduced skin photosensitization

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was “double-locked” by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the “double-key”, which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor‐Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity (Small 34/2022)

Cancer Phototherapy The endoplasmic reticulum (ER) plays an important role in protein synthesis, processing and secretion. ER-targeting phototherapy significantly amplifies ER stress, promotes tumor antigen release, and elicits a robust immunogenic cell death. In article number 2202728 by Weidong Wang, Junping Wang, Shenglin Luo, and co-workers, a small molecular heptamethine cyanine photosensitizer with binitro-substituted benzenesulfonamide (ER-Cy-poNO2) is designed and synthesized for tumor photodynamic therapy/photothermal therapy/immunotherapy by targeting the ER.

Self-Sacrificially Degradable Pseudo-Semiconducting Polymer Nanoparticles that Integrate NIR-II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo-Activated Chemotherapy.

Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self-sacrificially biodegradable pseudo-semiconducting polymer (PSP) for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co-assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)-responsive thioketal linkages (PEDOX ), which are denoted as NP@PEDOX /PSP. The NP@PEDOX /PSP can accumulate at tumor sites and generateROSfor photodynamic immunotherapy as well as near-infrared-II fluorescence (NIR-II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PEDOX , resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PEDOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PEDOX /PSP. This work highlights the application of self-sacrificially degradable PSP for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy.

Modulated plasmonic nanofibrous scaffold reinforced breast cancer photo-ablation and breast neurotization with resensation

Herein, we report the bioactivity of the hybrid plasmonic aligned nanofibrous scaffolds composed of reduced graphene oxide (rGO, 209 nm) nanosheets enfolded gold nanorods (AuNR) with polycaprolactone (PCL) for breast cancer photo-therapy and subsequent nerve regeneration. The strategic inclusion of 0.00068 wt% (OD = 4.0) of monodispersed AuNR-rGO in PCL (AuNR-rGO@PCL (4.0)) leads to significant higher physicochemical and optical properties such as higher mechanical strength (7-fold increase), electrical conductivity (∼6-times enhancement), larger surface area (6.4 times), and more NIR light absorbance. Hence, the AuNR-rGO@PCL (4.0) was found to be an excellent photo agent for breast tumor ablation with more than 90% cancer cell (MCF-7) death under 808 nm NIR irradiation at low laser power density (0.72 W/cm2). Also, the nanofibrous scaffold was observed to have a substantial effect on adhesion, proliferation, growth, and differentiation of PC12 and high affinity to S42 cell proliferation and migration which led to an exceptional nerve growth with a 2.5-fold (with NIR light after 3 days) and 2-fold (without NIR light after 7 days) increase in neurite length in comparison to PCL. The present study provides a new bioactive, biocompatible, non-toxic, and bifunctional aligned plasmonic scaffolds as an excellent single platform for breast cancer treatment and potential bioimplant to regain sensation loss after breast surgery and reconstruction.

Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor-Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity.

Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor-targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)-targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron-donating or -withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet-triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro-substituted benzenesulfonamide (ER-Cy-poNO2 ) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer-targeted immunotherapy.

A NTR and O2 programmed responsive photogenic radicals for efficient hypoxia cancer therapy

Stimulus responsive photodynamic therapy has attracted much attention. Although many methods have been proposed to alleviate the impact of hypoxia on photodynamic therapy (PDT), hypoxia is still one of the biggest obstacles to the efficient photodynamic treatment of tumors. Herein, a novel kind of nitroreductase (NTR) and O2 programmed responsive photosensitizer Eos-NO2 was developed to achieve precise and efficient PDT of hypoxia tumor. Specifically, the PDT “off” state Eos-NO2 was activated by the overexpressed NTR in tumor region to form PDT “on” state Eos. Then, the produced Eos in hypoxia could further generate the active free radicals and singlet oxygen for the efficient treatment of hypoxic tumors owing to photo-induced free radical process. Both in vitro and in vivo results confirm that such a NTR and O2 programmed responsive photosensitizer Eos-NO2 shows high specificity and selectivity for hypoxic solid tumor, presenting good prospects in the clinical cancer phototherapy.

Vehicle-Free Nanotheranostic Self-Assembled from Clinically Approved Dyes for Cancer Fluorescence Imaging and Photothermal/Photodynamic Combinational Therapy.

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted growing attention as a noninvasive option for cancer treatment. At present, researchers have developed various “all-in-one” nanoplatforms for cancer imaging and PTT/PDT combinational therapy. However, the complex structure, tedious preparation procedures, overuse of extra carriers and severe side effects hinder their biomedical applications. In this work, we reported a nanoplatform (designated as ICG-MB) self-assembly from two different FDA-approved dyes of indocyanine green (ICG) and methylene blue (MB) without any additional excipients for cancer fluorescence imaging and combinational PTT/PDT. ICG-MB was found to exhibit good dispersion in the aqueous phase and improve the photostability and cellular uptake of free ICG and MB, thus exhibiting enhanced photothermal conversion and singlet oxygen (1O2) generation abilities to robustly ablate cancer cells under 808 nm and 670 nm laser irradiation. After intravenous injection, ICG-MB effectively accumulated at tumor sites with a near-infrared (NIR) fluorescence signal, which helped to delineate the targeted area for NIR laser-triggered phototoxicity. As a consequence, ICG-MB displayed a combinational PTT/PDT effect to potently inhibit tumor growth without causing any system toxicities in vivo. In conclusion, this minimalist, effective and biocompatible nanotheranostic would provide a promising candidate for cancer phototherapy based on current available dyes in clinic.

Boosting phototherapy efficacy of NIR-absorbing ruthenium (II) complex via supramolecular engineering

Molecular aggregation of a well-designed photosensitizer has the potential to minimize its energy gap (ΔEST), thereby promoting the intersystem crossing rate, as well as singlet oxygen (1O2) generation. In light of this characteristic, a supramolecular photosensitizer (RuFF-NPs) has been fabricated through the noncovalent interaction of a Ru(II)-based complex (RuTP) and diphenylalanine peptide (FF). In contrast to the monomer of RuTP, RuFF-NPs showed excellent water dispersity, aggregation-enhanced 1O2 generation, remarkable red-shifted absorption, improved biocompatibility, and efficient dual phototherapeutic performance, which are highly desired characteristics for phototherapy. In cancer phototherapy, RuFF-NPs exhibited a much high tumor growth inhibition rate of 95.3% in vivo. Conspicuously, the tumor penetration and spatial distribution of RuFF-NPs with time were visually imaged at the molecular level, and the potential biochemical response was demonstrated, providing valuable information for elucidating the underlying anticancer mechanisms of phototherapy.